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| Name | Class |
|---|---|
| Immune Tolerance Network (ITN) | NETWORK |
| PPD Development, LP | INDUSTRY |
| Rho Federal Systems Division, Inc. | INDUSTRY |
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The primary aim of this study is to determine whether a peripheral blood or graft lymphocyte phenotype of immune senescence or exhaustion is different between operationally tolerant and non-tolerant liver allograft recipients.
People who have liver transplants must take anti-rejection medication (immunosuppression) for the rest of their lives. If they stop, their immune system may reject the transplanted liver. All anti-rejection medications have side effects. Because of the side effects of anti-rejection medications, an important goal of transplant research is to allow people to accept their transplanted organ without long term use of anti-rejection medications. This is called tolerance. In this study, participants who received a liver transplant will have their anti-rejection medication(s) gradually reduced over a period of time and then stopped. The study calls this 'immunosuppression withdrawal'.
The purpose of this research study is to see how many people will develop tolerance after immunosuppression withdrawal. The researchers also want to find out if there are blood or liver biopsy tests that can help transplant doctors in the future predict whether it is safe to decrease or stop anti-rejection medications in people who received a liver transplant.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Immunosuppression withdrawal (ISW) | Other | Gradual immunosuppression withdrawal according to the protocol defined algorithm |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Immunosuppression withdrawal | Biological | Participants will initiate calcineurin inhibitor (CNI) withdrawal after at least 3 weeks of stable liver function, as documented by liver function tests (direct bilirubin, alanine aminotransferase and gamma-glutamyl transferase) separated by at least 1 week in the 3 week period prior to withdrawal. CNI withdrawal will occur in eight 3 week intervals with each subsequent reduction based on liver function tests over the prior 3 week interval. Participants on CNI and prednisone will undergo withdrawal from the two therapies concurrently. If participants are weaned off the CNI successfully, they will initiate non-CNI withdrawal. The non-CNI withdrawal includes two dose reductions of approximately 50% over a 6 week period each, after which the drug will be discontinued. |
| Measure | Description | Time Frame |
|---|---|---|
| The Percent of Participants Who Achieve Operational Tolerance 52 Weeks After Completion of Immunosuppression Withdrawal. | Participants are considered as successfully withdrawn from immunosuppression if they remain off immunosuppression for at least 52 weeks without evidence of rejection since enrollment and have a liver biopsy at 52 weeks following completion of immunosuppression withdrawal demonstrating histological stability and the absence of rejection per Banff global assessment criteria. This biopsy is assessed by the central pathologist. All participants who fail to complete immunosuppression withdrawal, regardless of reason, or fail to have a biopsy 52 weeks after completion of immunosuppression withdrawal will be considered to have failed. | From initiation of immunosuppression withdrawal through 52 weeks after stopping all immunosuppression |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Participants Who Develop Donor-Specific AlloAbs (DSA) or de Novo Anti-human Leukocyte Antigen Human Leukocyte Antigen (HLA) Antibodies | HLA is a molecule formed by a complex of genes which encode cell-surface proteins responsible for the regulation of the immune system. This molecule is unique for each individual. HLA molecules are present in all cells and are responsible for helping the immune system distinguish between your own cells and foreign cells (like pathogens). However, when our immune system encounters HLA molecules from another individual (like during pregnancy, after blood transfusions or transplantation) it recognizes this as foreign and can generate anti-HLA antibodies. These anti-HLA antibodies could cause harm to the transplanted organ by recognizing its cells as foreign triggering the immune system to attack. This endpoint looks at the development of newly developed donor-specific antibodies (DSA). DSA are a subset of anti-HLA antibodies that are specific against the donor organ. These anti-HLA antibodies are categorized into two classes-class I and class II. The data shown is only for class II DSA. |
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Inclusion Criteria:
Recipient participants must meet all of the following criteria to be eligible for this study:
At the time of screening:
Recipient of either deceased or living donor liver transplant. Recipients of living donor transplants must have a donor who is also willing to enroll
Recipient of single organ transplant only
Must have a screening liver biopsy that fulfills the following criteria based on the central pathology reading:
Liver function tests (Direct bilirubin, alanine aminotransferase (ALT)), less than twice the upper limit of normal (ULN). ULN values for liver function tests will be defined by ranges from Harrison's Principles of Internal Medicine, 18th edition
Receiving calcineurin inhibitor (CNI) based maintenance immunosuppression. Participants may also concurrently receive:
Ability to sign informed consent
Living donor participants must meet all of the following criteria to be eligible for this study:
Exclusion Criteria:
Recipient participants who meet any of the following criteria will not be eligible for this study:
History of hepatitis C virus (HCV) infection (defined as a positive HCV antibody test)
Positive antigen-antibody immunoassay for human immunodeficiency virus, HIV-1/2
Serum positivity for HBV surface antigen or HBV-DNA
History of immune-mediated liver disease in which immunosuppression discontinuation is inadvisable (autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis)
Any medical condition associated with a likely need for systemic corticosteroid administration, e.g., reactive airways disease
Prospective baseline liver biopsy showing any of the following: (see recipient inclusion criteria #4)
Rejection within the 52 weeks prior to screening
Estimated glomerular filtration rate (GFR) <40 ml/min as calculated by CKD-EPI method (to mitigate the risk of worsening renal failure should rejection occur and high level of CNI be required)
The need for chronic anti-coagulation that cannot be safely discontinued for a minimum of 1 week to safely perform a liver biopsy
Pregnant females and females of childbearing age who are not using an effective method of birth control
Current drug or alcohol dependency
Inability to comply with the study visit schedule and required assessments, including frequent liver function monitoring and protocol biopsies
Inability to comply with study directed treatment
Any medical condition that in the opinion of the principal investigator would interfere with safe completion of the trial
Participation in another interventional clinical trial within the 4 weeks prior to screening
Living donor participants who meet any of the following criteria will not be eligible for this study:
1. Any medical condition, such as anemia, coagulopathy, etc., that in the opinion of the principal investigator would interfere with safe participation in the trial
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| Name | Affiliation | Role |
|---|---|---|
| James F. Markmann, MD, PhD | Massachusetts General Hospital: Transplantation | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, San Francisco Medical Center | San Francisco | California | 94143 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26729653 | Derived | Sanchez-Fueyo A, Markmann JF. Immune Exhaustion and Transplantation. Am J Transplant. 2016 Jul;16(7):1953-7. doi: 10.1111/ajt.13702. Epub 2016 Feb 16. |
| Label | URL |
|---|---|
| ITN OPTIMAL Study Website | View source |
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Informed consent was obtained from potentially eligible individuals who then underwent a study-mandated biopsy to determine if they were allowed to initiate immunosuppression withdrawal based on pre-specified histological criteria.
100 participants were enrolled from 7 sites in the US between December 2015 and November 2018. 61 of the enrolled participants were eligible to initiate immunosuppression withdrawal and the remaining 39 participants were terminated (e.g., ineligible to initiate immunosuppression withdrawal) based on biopsy findings or other pre-specified criteria.
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| ID | Title | Description |
|---|---|---|
| FG000 | Enrolled, Did Not Initiate Immunosuppression Withdrawal | Theses participants were consented and enrolled into the study, but did not initiate immunosuppression withdrawal as specified by the protocol. |
| FG001 | Initiated Immunosuppression Withdrawal |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 15, 2020 | Feb 10, 2021 |
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| From initiation of immunosuppression withdrawal to study completion, up to 4.5 years. |
| The Incidence of Acute Rejection, Steroid Resistant Rejection, and Chronic Rejection | Incidence will be measured as the proportion of participants who have acute rejection (per Banff criteria), steroid resistant rejection (rejection requiring antibody treatment), and chronic rejection (per Banff criteria), separately. The endpoint is summarized with a two-sided, 95% exact binomial confidence interval. | From initiation of immunosuppression withdrawal to study completion, up to 4.5 years. |
| The Severity of Acute Rejection, Steroid Resistant Rejection, and Chronic Rejection | Severity is based on the Banff global assessment grade according to the central pathology reading of the liver biopsy. For an individual subject, the worst severity is reported. Acute rejection is categorized into mild (rejection infiltrate in a minority of triads that is generally mild and confined within the portal spaces), moderate (rejection infiltrate expanding most or all of the triads), or severe (rejection infiltrate expanding most or all of the triads with spillover into periportal areas and moderate to severe perivenular inflammation that extends into the hepatic parenchyma and is associated with perivenular hepatocyte necrosis). Chronic rejection is categorized into early (bile duct atrophy/loss and foam cell obliterative arteriopathy in <50% of the portal tracts) or late (early criteria but >50% of the portal tracts) stage. Steroid resistant rejection is always considered severe. The endpoint is summarized with a two-sided, 95% exact binomial confidence interval. | From initiation of immunosuppression withdrawal to study completion, up to 4.5 years. |
| The Timing of Acute Rejection, Steroid Resistant Rejection, and Chronic Rejection | Time is measured as the time (in days) from the initiation of immunosuppression withdrawal to the time of the first biopsy showing rejection (per Banff criteria). | From initiation of immunosuppression withdrawal to study completion, up to 4.5 years. |
| The Incidence of Graft Fibrosis in Tolerant Versus Non- Tolerant Patients. | Fibrosis of the liver is the formation of an excessive accumulation of scar tissue in the liver. Graft fibrosis was measured two ways by the ISHAK scale and by Liver Allograft Fibrosis Score (LAFSc) via a liver biopsy. Both scales range from 0 to 6, with a higher score indicating more severe fibrosis. A subject is considered as having graft fibrosis if the score is greater than or equal to 2 at their last available biopsy after the initiation of immunosuppression withdrawal. | From initiation of immunosuppression withdrawal to study completion, up to 4.5 years. |
| The Progression of Graft Fibrosis in Tolerant Versus Non- Tolerant Patients | Fibrosis of the liver is the formation of an excessive accumulation of scar tissue in the liver. Graft fibrosis was measured two ways by the ISHAK scale and by Liver Allograft Fibrosis Score (LAFSc) via a liver biopsy. Both scales range from 0 to 6, with a higher score indicating more severe fibrosis. Progression was calculated as the final available biopsy score minus the baseline biopsy score. A positive value indicates a worsening of fibrosis. | From initiation of immunosuppression withdrawal to study completion, up to 4.5 years. |
| The Incidence of Graft Loss | A participant is considered to have graft loss when the donated liver needs to be removed and the participant is retransplanted with another donor liver or the participant is listed for retransplant. The endpoint will be summarized with a two-sided, 95% exact binomial confidence interval. | From initiation of immunosuppression withdrawal to study completion, up to 4.5 years. |
| The Incidence of All-Cause Mortality | This number reflects all deaths observed in all participants in the study period, regardless of the cause. The endpoint will be summarized with a two-sided, 95% exact binomial confidence interval. | From initiation of immunosuppression withdrawal to study completion, up to 4.5 years. |
| The Incidence of Study-related SAEs | An adverse event is considered a serious adverse event (SAE) if it results it any one of the following: death, life-threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substation disruption to conduct normal life functions, congenital anomaly or birth defect, or an important medical event. The event is considered study related if the medical monitor deems it to be at least possibly or definitely related to any of the study interventions/procedures (immunosuppression withdrawal, the blood draw, or the liver biopsy). The endpoint will be summarized with a two-sided, 95% exact binomial confidence interval. | From initiation of immunosuppression withdrawal to study completion, up to 4.5 years. |
| The Proportion of Operationally Tolerant Subjects Who Remain Free of Rejection at 3 Years After Completing Immunosuppression Withdrawal. | Participants are considered operationally tolerant if they remain off immunosuppression for at least 52 weeks without evidence of rejection since enrollment and have a liver biopsy at 52 weeks following completion of immunosuppression withdrawal demonstrating histological stability and the absence of rejection per Banff global assessment criteria (as assessed by the central pathologist). This number reflects the participants that continue to show the absence of rejection per the Banff global assessment criteria (as assessed by the central pathologist) in the 3 years following completion of immunosuppression withdrawal. The endpoint will be summarized with a two-sided, 95% exact binomial confidence interval. | From initiation of immunosuppression withdrawal through 3 years after completing immunosuppression withdrawal. |
| Changes in Renal Function (Defined as Estimated GFR Calculated by the CKD-EPI Creatine Equation 2021) in Tolerant Versus Non-tolerant Participants at 1, 2 and 3 Years After Completing Immunosuppression Withdrawal. | Glomerular filtration rate (GFR) is a measure of kidney function and helps determine the stage of kidney disease. A value less than 15 indicates kidney failure, 15 to 29 indicates severe loss of kidney function, 30 to 44 indicates moderate to severe loss of kidney function, 45 to 59 mild to moderate loss of kidney function, 60 to 89 indicates mild loss of kidney function, and 90 or higher indicates normal kidney function. The equation developed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) is used to estimate GFR from serum creatinine. The baseline value was selected as the value collected immediately prior to the initiation of immunosuppression withdrawal. The year 1, 2, and 3, values are the values closest to and within 2 months of the expected date. Change was calculated as the year 1, 2, or 3 value minus baseline. A positive value indicates an increase in kidney function. | From initiation of immunosuppression withdrawal to study completion, up to 4.5 years. |
| Changes in Quality of Life in Tolerant Versus Non-tolerant Participants and in All Participants at Baseline Versus the End of Study Participation, as Measured by the NIDDK Liver Transplantation Database Quality of Life Form. | NIDDK Liver Transplantation Database Quality of Life Form is a patient-reported survey of patient health. The questionnaire is summarized into five domains-measures of disease (ranges from 0-21 with higher score indicating worse quality), psychological status (ranges from 0-5 with higher score indicating worse quality), personal function (ranges from 0-4 with higher score indicating better quality), social and role function (ranges from 0 to 20 with higher score indicating worse quality), and general health perception (ranges from 0 to 10 with higher score indicating better quality). Change was calculated as the difference between the questionnaire completed at the initiation of withdrawal and the questionnaire completed closest to the end of study participation. This change was calculated separately for tolerant and non-tolerant subjects. | From initiation of immunosuppression withdrawal to study completion, up to 4.5 years. |
| Changes in SF-36 in Tolerant Versus Non-tolerant Participants and in All Participants at Baseline Versus the End of Study Participation. | SF-36 is a patient-reported survey of patient health. There are eight different scales that can be summarized into two summary scores-Mental Component Score and Physical Component Score. Each score ranges from 0-100, with a higher score indicating a better quality of life. Change was calculated as the difference between the questionnaire completed at the initiation of withdrawal and the questionnaire completed closest to the end of study participation. This change was calculated separately for tolerant and non-tolerant subjects. | From initiation of immunosuppression withdrawal to study completion, up to 4.5 years. |
| Predictive Value of the Following Parameters With Regard to Operational Tolerance: Time Post-transplant. | Time post-transplant is calculated as time in years from transplant to enrollment. Participants are considered operationally tolerant if they remain off immunosuppression for at least 52 weeks without evidence of rejection since enrollment and have a liver biopsy at 52 weeks following completion of immunosuppression withdrawal demonstrating histological stability and the absence of rejection per Banff global assessment criteria (as assessed by the central pathologist). The odds ratio and corresponding 95% confidence interval are presented. The odds ratio represents the probability of achieving operational tolerance per year increase in time post-transplant. An odds ratio greater than 1 means that as the factor increases, operational tolerance is more likely to occur. Whereas less than 1 means operational tolerance is less likely to occur. Since the confidence interval contains 1, this means that as the corresponding factor increases, the likelihood of tolerance does not change. | From initiation of immunosuppression withdrawal to study completion, up to 4.5 years. |
| Predictive Value and the Correlative Value of the Following Parameters With Regard to Operational Tolerance: Recipient Age. | Recipient age is the age at the time of enrollment. Participants are considered operationally tolerant if they remain off immunosuppression for at least 52 weeks without evidence of rejection since enrollment and have a liver biopsy at 52 weeks following completion of immunosuppression withdrawal demonstrating histological stability and the absence of rejection per Banff global assessment criteria (as assessed by the central pathologist). The odds ratio and corresponding 95% confidence interval are presented. The odds ratio represents the probability of achieving operational tolerance per year increase in recipient age. An odds ratio greater than 1 means that as the factor increases, operational tolerance is more likely to occur. Whereas less than 1 means operational tolerance is less likely to occur. Since the confidence interval contains 1, this means that as the corresponding factor increases, the likelihood of tolerance does not change. | From initiation of immunosuppression withdrawal to study completion, up to 4.5 years. |
| Northwestern University Feinberg School of Medicine |
| Chicago |
| Illinois |
| 60611 |
| United States |
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| Columbia University Medical Center | New York | New York | 10032 | United States |
| Hospital of the University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| University of Pittsburgh Medical Center | Pittsburgh | Pennsylvania | 15213 | United States |
| Baylor University Medical Center at Dallas | Dallas | Texas | 75246 | United States |
| Division of Allergy, Immunology, and Transplantation (DAIT) | View source |
| National Institute of Allergy and Infectious Diseases (NIAID) | View source |
| Immune Tolerance Network (ITN) | View source |
These participants were enrolled into the study and initiated immunosuppression withdrawal per protocol. Participants could initiate withdrawal from calcineurin inhibitor (CNI) monotherapy or combination therapy with CNI and prednisone or CNI and a mycophenolate compound. Immunosuppression withdrawal followed a pre-specified process with the goal of achieving complete discontinuation of all immunosuppressive medication between 24 and 45 weeks after initiation of withdrawal. |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Enrolled, Did Not Initiate Immunosuppression Withdrawal | Theses participants were consented and enrolled into the study, but did not initiate immunosuppression withdrawal as specified by the protocol. |
| BG001 | Initiated Immunosuppression Withdrawal | These participants were enrolled into the study and initiated immunosuppression withdrawal per protocol. Participants could initiate withdrawal from calcineurin inhibitor (CNI) monotherapy or combination therapy with CNI and prednisone or CNI and a mycophenolate compound. Immunosuppression withdrawal followed a pre-specified process with the goal of achieving complete discontinuation of all immunosuppressive medication between 24 and 45 weeks after initiation of withdrawal. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Alanine Transaminase (ALT) | The average of two ALT results taken at screening and 7 (+/- 2 days) before initiation of immunosuppression withdrawal. Only participants that initiated immunosuppression withdrawal will have both measurements. Reference: A liver function test -Normal Value: 7- 41 U/L. | Only participants that initiated immunosuppression withdrawal will have both measurements. | Mean | Standard Deviation | U/L |
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| Gamma-glutamyl Transferase (GGT) | The average of two GGT results taken at screening and 7 (+/- 2 days) before initiation of immunosuppression withdrawal. Only participants that initiated immunosuppression withdrawal will have both measurements. Reference: A liver function test- Normal Value: 9 - 58 U/L | Only participants that initiated immunosuppression withdrawal will have both measurements. | Mean | Standard Deviation | U/L |
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| Time from transplant (years) | The time from transplant to study enrollment in years. | Mean | Standard Deviation | Years |
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| Estimated Glomerular filtration rate (eGFR) | The value collected immediately prior to the initiation of immunosuppression (IS) withdrawal. Only subjects that initiated IS withdrawal will have this measurement (unit of measure of mL/min/1.73m2). eGFR was estimated using the CKD-EPI Creatine Equation (2021). eGFR is a measure of kidney function & helps determine disease stage. A value < 15 indicates kidney failure, 15-29 severe loss of kidney function, 30-44 moderate to severe loss of kidney function, 45-59 mild to moderate loss of kidney function, 60-89 mild loss of kidney function, and 90+ indicates normal kidney function. | Only subjects that initiated immunosuppression withdrawal will have this measurement. | Mean | Standard Deviation | mL/min/1.73 m2 |
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| Fibrosis Score (ISHAK) | The value collected on the baseline biopsy prior to the initiation of immunosuppression withdrawal. Only subjects that initiated immunosuppression withdrawal will have this measurement. The ISHAK score is a measurement of fibrosis (scarring of tissue) in the liver. This scale ranges from 0 to 6, with a higher score indicating more severe fibrosis. | Only subjects that initiated immunosuppression withdrawal will have this measurement. | Number | Percent of participants |
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| Liver Allograft Function Score (LAFSc) | The value collected on the baseline biopsy prior to the initiation of immunosuppression withdrawal. Only subjects that initiated immunosuppression withdrawal will have this measurement. The LAFSc score is a measurement of fibrosis (scarring of tissue) in the liver. This scale ranges from 0 to 6, with a higher score indicating more severe fibrosis | Only subjects that initiated immunosuppression withdrawal will have this measurement. | Number | Percent of participants |
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| NIDDK Liver Transplantation Database Quality of Life | The value collected prior to the initiation of immunosuppression withdrawal (ISW). Only subjects that initiated ISW have this measurement. This is a patient-reported survey of health and is summarized into five domains-measures of disease (0-21 with higher score indicating worse quality), psychological status (0-5 with higher score indicating worse quality), personal function (0-4 with higher score indicating better quality), social and role function (0-20 with higher score indicating worse quality), and general health perception (0-10 with higher score indicating better quality). | Only subjects that initiated immunosuppression withdrawal will have this measurement | Mean | Standard Deviation | NIDDK QOL Score |
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| SF-36 | The value collected immediately prior to the initiation of immunosuppression withdrawal. Only subjects that initiated immunosuppression withdrawal will have this measurement. The 36-Item Short Form Survey (SF-36) is a patient-reported questionnaire to measure quality of life. There are eight different scales that can be summarized into two summary scores-Mental Component Score (MCS) and Physical Component Score (PCS). Each score ranges from 0-100, with a higher score indicating a better quality of life. | Only subjects that initiated immunosuppression withdrawal will have this measurement. | Mean | Standard Deviation | SF-36 Component Score |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | The Percent of Participants Who Achieve Operational Tolerance 52 Weeks After Completion of Immunosuppression Withdrawal. | Participants are considered as successfully withdrawn from immunosuppression if they remain off immunosuppression for at least 52 weeks without evidence of rejection since enrollment and have a liver biopsy at 52 weeks following completion of immunosuppression withdrawal demonstrating histological stability and the absence of rejection per Banff global assessment criteria. This biopsy is assessed by the central pathologist. All participants who fail to complete immunosuppression withdrawal, regardless of reason, or fail to have a biopsy 52 weeks after completion of immunosuppression withdrawal will be considered to have failed. | Participants who initiated immunosuppression withdrawal | Posted | Number | 95% Confidence Interval | Percent of Participants | From initiation of immunosuppression withdrawal through 52 weeks after stopping all immunosuppression |
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| Secondary | Proportion of Participants Who Develop Donor-Specific AlloAbs (DSA) or de Novo Anti-human Leukocyte Antigen Human Leukocyte Antigen (HLA) Antibodies | HLA is a molecule formed by a complex of genes which encode cell-surface proteins responsible for the regulation of the immune system. This molecule is unique for each individual. HLA molecules are present in all cells and are responsible for helping the immune system distinguish between your own cells and foreign cells (like pathogens). However, when our immune system encounters HLA molecules from another individual (like during pregnancy, after blood transfusions or transplantation) it recognizes this as foreign and can generate anti-HLA antibodies. These anti-HLA antibodies could cause harm to the transplanted organ by recognizing its cells as foreign triggering the immune system to attack. This endpoint looks at the development of newly developed donor-specific antibodies (DSA). DSA are a subset of anti-HLA antibodies that are specific against the donor organ. These anti-HLA antibodies are categorized into two classes-class I and class II. The data shown is only for class II DSA. | Initiated immunosuppression withdrawal and have analyzable blood samples prior to and after initiating withdrawal | Posted | Number | 95% Confidence Interval | Percent of participants | From initiation of immunosuppression withdrawal to study completion, up to 4.5 years. |
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| Secondary | The Incidence of Acute Rejection, Steroid Resistant Rejection, and Chronic Rejection | Incidence will be measured as the proportion of participants who have acute rejection (per Banff criteria), steroid resistant rejection (rejection requiring antibody treatment), and chronic rejection (per Banff criteria), separately. The endpoint is summarized with a two-sided, 95% exact binomial confidence interval. | Participants who initiated immunosuppression withdrawal | Posted | Number | 95% Confidence Interval | Percent of participants | From initiation of immunosuppression withdrawal to study completion, up to 4.5 years. |
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| Secondary | The Severity of Acute Rejection, Steroid Resistant Rejection, and Chronic Rejection | Severity is based on the Banff global assessment grade according to the central pathology reading of the liver biopsy. For an individual subject, the worst severity is reported. Acute rejection is categorized into mild (rejection infiltrate in a minority of triads that is generally mild and confined within the portal spaces), moderate (rejection infiltrate expanding most or all of the triads), or severe (rejection infiltrate expanding most or all of the triads with spillover into periportal areas and moderate to severe perivenular inflammation that extends into the hepatic parenchyma and is associated with perivenular hepatocyte necrosis). Chronic rejection is categorized into early (bile duct atrophy/loss and foam cell obliterative arteriopathy in <50% of the portal tracts) or late (early criteria but >50% of the portal tracts) stage. Steroid resistant rejection is always considered severe. The endpoint is summarized with a two-sided, 95% exact binomial confidence interval. | Participants who had acute, steroid-resistant, or chronic rejection. | Posted | Number | 95% Confidence Interval | Percent of participants | From initiation of immunosuppression withdrawal to study completion, up to 4.5 years. |
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| Secondary | The Timing of Acute Rejection, Steroid Resistant Rejection, and Chronic Rejection | Time is measured as the time (in days) from the initiation of immunosuppression withdrawal to the time of the first biopsy showing rejection (per Banff criteria). | Participants who had acute, steroid-resistant, or chronic rejection.Time to event data could not be reported as no events were observed for Chronic Rejection and Steroid Resistant Rejection | Posted | Mean | Standard Deviation | Days | From initiation of immunosuppression withdrawal to study completion, up to 4.5 years. |
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| Secondary | The Incidence of Graft Fibrosis in Tolerant Versus Non- Tolerant Patients. | Fibrosis of the liver is the formation of an excessive accumulation of scar tissue in the liver. Graft fibrosis was measured two ways by the ISHAK scale and by Liver Allograft Fibrosis Score (LAFSc) via a liver biopsy. Both scales range from 0 to 6, with a higher score indicating more severe fibrosis. A subject is considered as having graft fibrosis if the score is greater than or equal to 2 at their last available biopsy after the initiation of immunosuppression withdrawal. | Participants who initiated immunosuppression withdrawal and have a biopsy available after the initiation of immunosuppression withdrawal. | Posted | Number | 95% Confidence Interval | Percent of participants | From initiation of immunosuppression withdrawal to study completion, up to 4.5 years. |
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| Secondary | The Progression of Graft Fibrosis in Tolerant Versus Non- Tolerant Patients | Fibrosis of the liver is the formation of an excessive accumulation of scar tissue in the liver. Graft fibrosis was measured two ways by the ISHAK scale and by Liver Allograft Fibrosis Score (LAFSc) via a liver biopsy. Both scales range from 0 to 6, with a higher score indicating more severe fibrosis. Progression was calculated as the final available biopsy score minus the baseline biopsy score. A positive value indicates a worsening of fibrosis. | Participants who initiated immunosuppression withdrawal and have a biopsy available after the initiation of immunosuppression withdrawal. | Posted | Mean | Standard Deviation | Fibrosis Score | From initiation of immunosuppression withdrawal to study completion, up to 4.5 years. |
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| Secondary | The Incidence of Graft Loss | A participant is considered to have graft loss when the donated liver needs to be removed and the participant is retransplanted with another donor liver or the participant is listed for retransplant. The endpoint will be summarized with a two-sided, 95% exact binomial confidence interval. | Participants who initiated immunosuppression withdrawal | Posted | Number | 95% Confidence Interval | Percent of participants | From initiation of immunosuppression withdrawal to study completion, up to 4.5 years. |
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| Secondary | The Incidence of All-Cause Mortality | This number reflects all deaths observed in all participants in the study period, regardless of the cause. The endpoint will be summarized with a two-sided, 95% exact binomial confidence interval. | Participants who initiated immunosuppression withdrawal | Posted | Number | 95% Confidence Interval | Percent of participants | From initiation of immunosuppression withdrawal to study completion, up to 4.5 years. |
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| Secondary | The Incidence of Study-related SAEs | An adverse event is considered a serious adverse event (SAE) if it results it any one of the following: death, life-threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substation disruption to conduct normal life functions, congenital anomaly or birth defect, or an important medical event. The event is considered study related if the medical monitor deems it to be at least possibly or definitely related to any of the study interventions/procedures (immunosuppression withdrawal, the blood draw, or the liver biopsy). The endpoint will be summarized with a two-sided, 95% exact binomial confidence interval. | Participants who initiated immunosuppression withdrawal | Posted | Number | 95% Confidence Interval | Percent of participants | From initiation of immunosuppression withdrawal to study completion, up to 4.5 years. |
| |||||||||||||||||||||||||||
| Secondary | The Proportion of Operationally Tolerant Subjects Who Remain Free of Rejection at 3 Years After Completing Immunosuppression Withdrawal. | Participants are considered operationally tolerant if they remain off immunosuppression for at least 52 weeks without evidence of rejection since enrollment and have a liver biopsy at 52 weeks following completion of immunosuppression withdrawal demonstrating histological stability and the absence of rejection per Banff global assessment criteria (as assessed by the central pathologist). This number reflects the participants that continue to show the absence of rejection per the Banff global assessment criteria (as assessed by the central pathologist) in the 3 years following completion of immunosuppression withdrawal. The endpoint will be summarized with a two-sided, 95% exact binomial confidence interval. | Participants who achieved operational tolerance as defined by the primary endpoint. | Posted | Number | 95% Confidence Interval | Percent of participants | From initiation of immunosuppression withdrawal through 3 years after completing immunosuppression withdrawal. |
|
| ||||||||||||||||||||||||||
| Secondary | Changes in Renal Function (Defined as Estimated GFR Calculated by the CKD-EPI Creatine Equation 2021) in Tolerant Versus Non-tolerant Participants at 1, 2 and 3 Years After Completing Immunosuppression Withdrawal. | Glomerular filtration rate (GFR) is a measure of kidney function and helps determine the stage of kidney disease. A value less than 15 indicates kidney failure, 15 to 29 indicates severe loss of kidney function, 30 to 44 indicates moderate to severe loss of kidney function, 45 to 59 mild to moderate loss of kidney function, 60 to 89 indicates mild loss of kidney function, and 90 or higher indicates normal kidney function. The equation developed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) is used to estimate GFR from serum creatinine. The baseline value was selected as the value collected immediately prior to the initiation of immunosuppression withdrawal. The year 1, 2, and 3, values are the values closest to and within 2 months of the expected date. Change was calculated as the year 1, 2, or 3 value minus baseline. A positive value indicates an increase in kidney function. | Participants who initiated immunosuppression withdrawal | Posted | Mean | Standard Deviation | ml/min/1.73 m^2 | From initiation of immunosuppression withdrawal to study completion, up to 4.5 years. |
| |||||||||||||||||||||||||||
| Secondary | Changes in Quality of Life in Tolerant Versus Non-tolerant Participants and in All Participants at Baseline Versus the End of Study Participation, as Measured by the NIDDK Liver Transplantation Database Quality of Life Form. | NIDDK Liver Transplantation Database Quality of Life Form is a patient-reported survey of patient health. The questionnaire is summarized into five domains-measures of disease (ranges from 0-21 with higher score indicating worse quality), psychological status (ranges from 0-5 with higher score indicating worse quality), personal function (ranges from 0-4 with higher score indicating better quality), social and role function (ranges from 0 to 20 with higher score indicating worse quality), and general health perception (ranges from 0 to 10 with higher score indicating better quality). Change was calculated as the difference between the questionnaire completed at the initiation of withdrawal and the questionnaire completed closest to the end of study participation. This change was calculated separately for tolerant and non-tolerant subjects. | Participants who initiated immunosuppression withdrawal and completed a NIDDK Liver Transplantation Database Quality of Life survey at baseline and after immunosuppression withdrawal initiation. | Posted | Mean | Standard Deviation | Domain Score | From initiation of immunosuppression withdrawal to study completion, up to 4.5 years. |
| |||||||||||||||||||||||||||
| Secondary | Changes in SF-36 in Tolerant Versus Non-tolerant Participants and in All Participants at Baseline Versus the End of Study Participation. | SF-36 is a patient-reported survey of patient health. There are eight different scales that can be summarized into two summary scores-Mental Component Score and Physical Component Score. Each score ranges from 0-100, with a higher score indicating a better quality of life. Change was calculated as the difference between the questionnaire completed at the initiation of withdrawal and the questionnaire completed closest to the end of study participation. This change was calculated separately for tolerant and non-tolerant subjects. | Participants who initiated immunosuppression withdrawal and completed a SF-36 survey at baseline and after immunosuppression withdrawal initiation. | Posted | Mean | Standard Deviation | SF-36 Component Score | From initiation of immunosuppression withdrawal to study completion, up to 4.5 years. |
| |||||||||||||||||||||||||||
| Secondary | Predictive Value of the Following Parameters With Regard to Operational Tolerance: Time Post-transplant. | Time post-transplant is calculated as time in years from transplant to enrollment. Participants are considered operationally tolerant if they remain off immunosuppression for at least 52 weeks without evidence of rejection since enrollment and have a liver biopsy at 52 weeks following completion of immunosuppression withdrawal demonstrating histological stability and the absence of rejection per Banff global assessment criteria (as assessed by the central pathologist). The odds ratio and corresponding 95% confidence interval are presented. The odds ratio represents the probability of achieving operational tolerance per year increase in time post-transplant. An odds ratio greater than 1 means that as the factor increases, operational tolerance is more likely to occur. Whereas less than 1 means operational tolerance is less likely to occur. Since the confidence interval contains 1, this means that as the corresponding factor increases, the likelihood of tolerance does not change. | Participants who initiated immunosuppression withdrawal | Posted | Number | 95% Confidence Interval | Probability of operational tolerance | From initiation of immunosuppression withdrawal to study completion, up to 4.5 years. |
| |||||||||||||||||||||||||||
| Secondary | Predictive Value and the Correlative Value of the Following Parameters With Regard to Operational Tolerance: Recipient Age. | Recipient age is the age at the time of enrollment. Participants are considered operationally tolerant if they remain off immunosuppression for at least 52 weeks without evidence of rejection since enrollment and have a liver biopsy at 52 weeks following completion of immunosuppression withdrawal demonstrating histological stability and the absence of rejection per Banff global assessment criteria (as assessed by the central pathologist). The odds ratio and corresponding 95% confidence interval are presented. The odds ratio represents the probability of achieving operational tolerance per year increase in recipient age. An odds ratio greater than 1 means that as the factor increases, operational tolerance is more likely to occur. Whereas less than 1 means operational tolerance is less likely to occur. Since the confidence interval contains 1, this means that as the corresponding factor increases, the likelihood of tolerance does not change. | Participants who initiated immunosuppression withdrawal | Posted | Number | 95% Confidence Interval | Probability of operational tolerance | From initiation of immunosuppression withdrawal to study completion, up to 4.5 years. |
|
Up to 4.5 years
Prior to initiating immunosuppression withdrawal, only adverse events and serious adverse events associated with protocol-mandated blood draws or the screening biopsy will be collected from study enrollment until initiation of immunosuppression withdrawal.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Enrolled, Did Not Initiate Immunosuppression Withdrawal | Theses participants were consented and enrolled into the study, but did not initiate immunosuppression withdrawal as specified by the protocol. | 0 | 39 | 0 | 39 | 3 | 39 |
| EG001 | Initiated Immunosuppression Withdrawal | These participants were enrolled into the study and initiated immunosuppression withdrawal per protocol. Participants could initiate withdrawal from calcineurin inhibitor (CNI) monotherapy or combination therapy with CNI and prednisone or CNI and a mycophenolate compound. Immunosuppression withdrawal followed a pre-specified process with the goal of achieving complete discontinuation of all immunosuppressive medication between 24 and 45 weeks after initiation of withdrawal. | 2 | 61 | 27 | 61 | 53 | 61 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Haemolytic anaemia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Normochromic normocytic anaemia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Arrhythmia | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Atrioventricular block | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Atrioventricular block complete | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Cardiac failure acute | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Hyperthyroidism | Endocrine disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Diplopia | Eye disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Abdominal hernia | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Intestinal ischaemia | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Large intestine perforation | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Parotid gland enlargement | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Umbilical hernia | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Gait disturbance | General disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Incarcerated hernia | General disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Bile duct stenosis | Hepatobiliary disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Haemobilia | Hepatobiliary disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Hepatic artery stenosis | Hepatobiliary disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Intrahepatic portal hepatic venous fistula | Hepatobiliary disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Transplant rejection | Immune system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Abdominal wall abscess | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Acute sinusitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Chlamydial infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Diverticulitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Gastroenteritis norovirus | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Gingivitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Hand-foot-and-mouth disease | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Hepatitis B | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Herpes virus infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Lyme disease | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Medical device site joint infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Pharyngitis streptococcal | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Post procedural cellulitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Rhinovirus infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Tooth infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Vulvovaginal mycotic infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Ankle fracture | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
| |
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
| |
| Concussion | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
| |
| Exposure to toxic agent | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
| |
| Hand fracture | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
| |
| Incisional hernia | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
| |
| Meniscus injury | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
| |
| Post procedural discomfort | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
| |
| Procedural nausea | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
| |
| Rib fracture | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
| |
| Synovial rupture | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
| |
| Transplant dysfunction | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Blood glucose increased | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Cardiac murmur | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Laboratory test abnormal | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Liver function test abnormal | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Fluid overload | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Gout | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Type 2 diabetes mellitus | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Joint effusion | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 14.0 | Systematic Assessment |
| |
| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 14.0 | Systematic Assessment |
| |
| Squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 14.0 | Systematic Assessment |
| |
| Aphasia | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Autonomic nervous system imbalance | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Lumbar radiculopathy | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Migraine | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Mental status changes | Psychiatric disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Chronic kidney disease | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Prostatitis | Reproductive system and breast disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Sleep apnoea syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Dermatitis atopic | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Aortic stenosis | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Orthostatic hypotension | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Chest Pain | General disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Corona virus infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Extremity necrosis | Vascular disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Wound | Injury, poisoning and procedural complications | MedDRA (14.0) | Systematic Assessment |
| |
| Ageusia | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Amnesia | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Knee arthroplasty | Surgical and medical procedures | MedDRA (14.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Haemolytic anaemia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Normochromic normocytic anaemia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Arrhythmia | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Atrioventricular block | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Atrioventricular block complete | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Cardiac failure acute | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Hyperthyroidism | Endocrine disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Diplopia | Eye disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Abdominal hernia | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Intestinal ischaemia | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Large intestine perforation | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Parotid gland enlargement | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Umbilical hernia | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Gait disturbance | General disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Incarcerated hernia | General disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Bile duct stenosis | Hepatobiliary disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Haemobilia | Hepatobiliary disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Hepatic artery stenosis | Hepatobiliary disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Intrahepatic portal hepatic venous fistula | Hepatobiliary disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Transplant rejection | Immune system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Abdominal wall abscess | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Acute sinusitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Chlamydial infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Diverticulitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Gastroenteritis norovirus | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Gingivitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Hand-foot-and-mouth disease | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Hepatitis B | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Herpes virus infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Lyme disease | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Medical device site joint infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Pharyngitis streptococcal | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Post procedural cellulitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Rhinovirus infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Tooth infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Vulvovaginal mycotic infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Ankle fracture | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
| |
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
| |
| Concussion | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
| |
| Exposure to toxic agent | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
| |
| Hand fracture | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
| |
| Incisional hernia | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
| |
| Meniscus injury | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
| |
| Post procedural discomfort | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
| |
| Procedural nausea | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
| |
| Rib fracture | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
| |
| Synovial rupture | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
| |
| Transplant dysfunction | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Blood glucose increased | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Cardiac murmur | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Laboratory test abnormal | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Liver function test abnormal | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Fluid overload | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Gout | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Type 2 diabetes mellitus | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Joint effusion | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 14.0 | Systematic Assessment |
| |
| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 14.0 | Systematic Assessment |
| |
| Squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 14.0 | Systematic Assessment |
| |
| Aphasia | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Autonomic nervous system imbalance | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Lumbar radiculopathy | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Migraine | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Mental status changes | Psychiatric disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Chronic kidney disease | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Prostatitis | Reproductive system and breast disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Sleep apnoea syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Dermatitis atopic | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Aortic stenosis | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Orthostatic hypotension | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Wound | Injury, poisoning and procedural complications | MedDRA (14.0) | Systematic Assessment |
| |
| Ageusia | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Amnesia | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Knee arthroplasty | Surgical and medical procedures | MedDRA (14.0) | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Corona virus infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Extremity necrosis | Vascular disorders | MedDRA (14.0) | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Director, Clinical Research Operations Program | DAIT/NIAID | 301-594-7669 | DAITClinicalTrialsGov@niaid.nih.gov |
| Prot_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 10, 2020 | Feb 9, 2021 | SAP_000.pdf |
| Between 18 and 65 years |
|
| >=65 years |
|
|
|
|
|
|
|
|
|
|
|
| 1 |
|
|
| 2 |
|
|
|
| 1 |
|
|
| 2 |
|
|
| 3 |
|
|
| 4 |
|
|
|
| Psychological status domain |
|
|
| Personal function domain |
|
|
| Social and role function domain |
|
|
| General health perception domain |
|
|
|
| MCS |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
| Participants |
|
|
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
|
Participants who initiated immunosuppression withdrawal and were deemed non-tolerant by the primary endpoint. |
|
|
| Initiated Immunosuppression Withdrawal (Non-tolerant) |
Participants who initiated immunosuppression withdrawal and were deemed non-tolerant by the primary endpoint. |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
|
|
|