Not provided
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The stopping rule for incidence of acute rejection was met.
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| Name | Class |
|---|---|
| Immune Tolerance Network (ITN) | NETWORK |
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The purpose of this study is see if a combination of two drugs, (ATG and rituximab), given at the time of the transplant surgery, will help reduce or eliminate the need for long term immunosuppressive medication.
Kidneys remove excess fluid and waste from the blood. When kidneys lose their filtering ability, dangerous levels of fluid and waste accumulate in the body - a condition known as kidney failure. There are two ways to treat kidney failure. One way is to get dialysis indefinitely. The second way is to get a kidney transplant. A kidney transplant is often the best treatment for kidney failure. A kidney transplant is a surgical procedure to place a healthy kidney from a donor into a person whose kidneys no longer function properly. This study is for people who will receive a kidney transplant from a very well matched, living blood relative. The immune system is the body's defense system against illness. After transplant, the immune system will think that the new kidney is a foreign invader and will try to attack or reject the transplanted kidney. Immunosuppressive drugs protect the transplanted kidney by suppressing the immune system. People who have kidney transplants must take immunosuppressive drug for the rest of their lives. If they stop, their immune system may reject the transplanted kidney. Immunosuppressive drugs make it hard for the body to fight off infections. In addition, they can cause high blood pressure, kidney damage, plaque build-up in the blood vessels, high cholesterol, diabetes and bone disease. They may also make the body more likely to get some types of cancer (mainly cancer of the white blood cells and/or skin) and other serious side effects.
Because of the side effects of immunosuppressive drugs, an important goal of transplant research is to allow people to accept their transplanted organ without always having to take immunosuppressive drugs. This is called tolerance. The RESTARRT study is testing a combination of two medications, rituximab and anti-thymocyte globulin (ATG), to see if they can help people reduce or eliminate the need for life-long immunosuppressive medications. ATG has been used for over 10 years to treat transplant rejection; rituximab is used to treat rheumatoid arthritis and two types of cancer. ATG works on immune cells called 'T cells' that are involved in transplant rejection, while rituximab works on a different type of cell called 'B cells.' Researchers hope that targeting both these cell types at the same time will help reset the immune system so that it accepts the transplanted kidney.
Frequent visits are required during the first two months of the study. Then, study visits take place about every 4 weeks, but more often (every 2 weeks) when reducing medication doses. After two years, participants will be asked to return for check-ups every 3 months. Study visits may include consultations with the transplant doctors, physical exam, blood and/or urine samples and kidney biopsies at several times during the study. In all, participation could last up to 4 years. All study-related medications and tests are provided at no charge to the patient.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Induction (Rituximab and ATG) | Experimental | Study participants will undergo induction with rituximab and ATG and an initial maintenance therapy with tacrolimus, mycophenolate mofetil (MMF) and sirolimus. MMF will be discontinued on day 12. Participants will be evaluated for eligibility for tacrolimus withdrawal which must be initiated between weeks 26 and 38. Tacrolimus withdrawal must be completed in no fewer than 4 weeks and no more than 8 weeks. Then after at least 26 weeks on sirolimus monotherapy, participants will be evaluated for eligibility for sirolimus withdrawal which must be initiated between weeks 56 and 88. Sirolimus withdrawal must be completed in no fewer than 12 weeks and no more than 26 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ATG | Drug | 1.5 mg/kg IV infusion on day of transplant, and 3 additional on days 2 through 7 after transplant. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percent of Participants Successfully Withdrawn From Immunosuppression and Remained Off Immunosuppression for at Least 52 Weeks | Participants are considered successfully withdrawn from immunosuppression if they remained off immunosuppression for at least 52 weeks without evidence of rejection, as determined by a biopsy performed 52 weeks after completion of immunosuppression withdrawal. All participants who failed to complete immunosuppression withdrawal, regardless of reason, or failed to have a biopsy 52 weeks after completion of immunosuppression withdrawal, were considered to have failed. The endpoint is summarized with a two-sided, 95% exact binomial confidence interval. | Transplantation through 52 weeks after discontinuation of all immunosuppression |
| Measure | Description | Time Frame |
|---|---|---|
| Percent of Transplanted Participants Who Remain Off Immunosuppression for at Least 52 Weeks Including Those in Whom the 52 Week Biopsy Was Not Performed | Participants are considered successfully withdrawn from immunosuppression if they remained off immunosuppression for at least 52 weeks without evidence of rejection. A biopsy performed 52 weeks after completion of immunosuppression withdrawal confirmed that there was no sub-clinical evidence of rejection. This result considers a participant off all immunosuppression for at least 52 weeks with or without the confirmatory week 52 biopsy as a success. The endpoint is summarized with a two-sided, 95% exact binomial confidence interval. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| James Markmann, MD, PhD | Massachusetts General Hospital | Principal Investigator |
| 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 |
|---|---|---|---|
| 18294345 | Background | Solez K, Colvin RB, Racusen LC, Haas M, Sis B, Mengel M, Halloran PF, Baldwin W, Banfi G, Collins AB, Cosio F, David DS, Drachenberg C, Einecke G, Fogo AB, Gibson IW, Glotz D, Iskandar SS, Kraus E, Lerut E, Mannon RB, Mihatsch M, Nankivell BJ, Nickeleit V, Papadimitriou JC, Randhawa P, Regele H, Renaudin K, Roberts I, Seron D, Smith RN, Valente M. Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant. 2008 Apr;8(4):753-60. doi: 10.1111/j.1600-6143.2008.02159.x. Epub 2008 Feb 19. |
| Label | URL |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) | View source |
Not provided
The plan is to provide data access to the public in the Immunology Database and Analysis Portal (ImmPort, http://www.immport.org/). ImmPort is a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
Not provided
After completion of the study.
Will be available to the public.
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Induction (Rituximab and ATG) | Adult living donor kidney transplant recipients were enrolled into the study prior to transplant. Participants received a novel induction regimen of ATG and rituximab that included 4 doses of ATG 1.5 mg/kg and 2 doses of rituximab 375 mg/m^2. The first dose of rituximab was given ~ day -6 pre-transplant, and the second dose on day 1-3 post-transplant. The first dose of ATG was given on the day of transplant, with the additional three doses administered on days 2-7 post-transplant (not on the same day as rituximab). Participants were maintained on anti-rejection medications tacrolimus, MMF, and sirolimus post-transplant. Participants were evaluated for eligibility to proceed with immunosuppressive maintenance withdrawal (IMW), a gradual withdrawal of their anti-rejection medications, starting as early as 26 weeks post-transplant. IMW for eligible participants proceeded with close monitoring per protocol over a period of 68-104 weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Participants that received induction (Rituximab and ATG) and were transplanted on study
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Induction (Rituximab and ATG) | Adult living donor kidney transplant recipients were enrolled into the study prior to transplant. Participants received a novel induction regimen of ATG and rituximab that included 4 doses of ATG 1.5 mg/kg and 2 doses of rituximab 375 mg/m^2. The first dose of rituximab was given ~ day -6 pre-transplant, and the second dose on day 1-3 post-transplant. The first dose of ATG was given on the day of transplant, with the additional three doses administered on days 2-7 post-transplant (not on the same day as rituximab). Participants were maintained on anti-rejection medications tacrolimus, MMF, and sirolimus post-transplant. Participants were evaluated for eligibility to proceed with immunosuppressive maintenance withdrawal (IMW), a gradual withdrawal of their anti-rejection medications, starting as early as 26 weeks post-transplant. IMW for eligible participants proceeded with close monitoring per protocol over a period of 68-104 weeks. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Percent of Participants Successfully Withdrawn From Immunosuppression and Remained Off Immunosuppression for at Least 52 Weeks | Participants are considered successfully withdrawn from immunosuppression if they remained off immunosuppression for at least 52 weeks without evidence of rejection, as determined by a biopsy performed 52 weeks after completion of immunosuppression withdrawal. All participants who failed to complete immunosuppression withdrawal, regardless of reason, or failed to have a biopsy 52 weeks after completion of immunosuppression withdrawal, were considered to have failed. The endpoint is summarized with a two-sided, 95% exact binomial confidence interval. | Participants that received induction (Rituximab and ATG) and were transplanted on study | Posted | Number | 95% Confidence Interval | Percent of participants | Transplantation through 52 weeks after discontinuation of all immunosuppression |
|
Transplantation through end of trial participation (up to 4.4 years post-transplant).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Transplanted | These are adult living donor kidney transplant recipients that were enrolled into the study prior to transplant and met all criteria for study participation. These participants received a novel induction regimen of ATG and rituximab that included 4 doses of ATG 1.5 mg/kg and 2 doses of rituximab 375 mg/m2. The first dose of rituximab was given around day -6 prior to transplant, and the second dose was given on day 1-3 post-transplant. The first dose of ATG was given on the day of transplant, with the additional three doses administered on days 2-7 post-transplant (not on the same day as rituximab). Participants were maintained on the anti-rejection medications tacrolimus, MMF, and sirolimus after transplant. Participants were evaluated for eligibility to start gradual withdrawal of their anti-rejection medications starting as early as 26 weeks post-transplant. Eligible participants were gradually withdrawn from anti-rejection medication over a period of 68-104 weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal hernia | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
The stopping rule for the incidence of rejection was met in December 2015, and enrollment was stopped in January 2016. After another rejection in May 2016, all participants were removed from protocol therapy and into reduced safety follow-up.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Director, Clinical Research Operations Program | DAIT/NIAID | 301-594-7669 | DAITClinicalTrialsGov@niaid.nih.gov |
Not provided
| ID | Term |
|---|---|
| C512542 | thymoglobulin |
| D000961 | Antilymphocyte Serum |
| D000069283 | Rituximab |
| D016559 | Tacrolimus |
| D020123 | Sirolimus |
| D009173 | Mycophenolic Acid |
| ID | Term |
|---|---|
| D007106 | Immune Sera |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
Not provided
Not provided
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Not provided
Not provided
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| Rituximab | Drug | 375 mg/m^2 IV infusion on day -6 before transplant and on day 1 after transplant. |
|
|
| Tacrolimus | Drug | Taken orally. Tacrolimus dose adjusted to maintain target blood levels of 6-10 ng/mL. |
|
|
| Sirolimus | Drug | Taken orally. Initial dose, 2 mg daily on day 10 post-transplant, subsequently adjusted to achieve trough levels of 8-12 ng/mL through week 56. Sirolimus withdrawal will be initiated between week 56 and week 88 in eligible participants. |
|
|
| MMF | Drug | 1 g twice daily on days 0 through 12 |
|
|
| Transplantation through 52 weeks after discontinuation of all immunosuppression |
| Percent of Transplanted Participants Who Remain Off Immunosuppression for the Duration of the Study as Defined as Completion of All Schedules of Events/Followed Through August 25, 2017 | Participants that remained off all immunosuppression through the completion of study participation. The endpoint is summarized with a two-sided, 95% exact binomial confidence interval. | Transplantation through study completion (up to 4.4 years post-transplant) |
| Percent of Transplanted Participants Who Achieve Sirolimus Monotherapy Within 52 Weeks Post-transplant | Participants that were treated with only sirolimus within 52 weeks after transplantation in those who could tolerant sirolimus. The endpoint is summarized with a two-sided, 95% exact binomial confidence interval. | Transplantation through 52 weeks post-transplantation |
| Percent of Transplanted Participants Who Achieve MMF or Mycophenolic Acid Monotherapy Within 52 Weeks Post-transplant in Those Participants Intolerant of Sirolimus | Participants that were treated with only mycophenolate mofetil (MMF) or mycophenolic acid within 52 weeks after transplantation in those who could not tolerate sirolimus. The endpoint is summarized with a two-sided, 95% exact binomial confidence interval. | Transplantation through 52 weeks post-transplantation |
| Percent of Transplanted Participants Who Achieve Either Sirolimus Monotherapy or Monotherapy on a Mycophenolic Compound Within 52 Weeks Post-transplant | Participants that were treated with only sirolimus or treated with only mycophenolate mofetil (MMF) or mycophenolic acid within 52 weeks after transplantation. The endpoint is summarized with a two-sided, 95% exact binomial confidence interval. | Transplantation through 52 weeks post-transplantation |
| Immunosuppression-free Duration in Days, Defined as Time From Completion of Immunosuppression Withdrawal to End of Trial Participation or to Time of Restarting Immunosuppression | Time (in days) from when the participant is off all immunosuppression to the end of trial participation or re-initiation of immunosuppression, whichever is earliest. | Transplantation through end of trial participation (up to 4.4 years post-transplant) |
| Time From Completion of Immunosuppression Withdrawal to First Episode of Acute Rejection or Presumed Acute Rejection | Time (in days) from when the participant is off all immunosuppression to the first episode of biopsy proven or presumed acute rejection. | Transplantation through end of trial participation (up to 4.4 years post-transplant) |
| Time From Completion of Immunosuppression Withdrawal to First Diagnosis of Chronic T Cell Mediated or Antibody-mediated Rejection | Time (in days) from the time the participant is off all immunosuppression to the first episode of chronic T cell mediated or chronic antibody-mediated rejection. This assessment also includes progressive interstitial fibrosis/tubular atrophy (IF/TA), transplant glomerulopathy or chronic obliterative arteriopathy without an alternative, non-rejection related cause. | Transplantation through end of trial participation (up to 4.4 years post-transplant) |
| Percent of Transplanted Participants With Graft Loss | A participant is considered to have graft loss when the donated kidney needs to be removed, the participant is retransplanted with another donor kidney, or chronic dialysis is instituted. The endpoint is summarized with a two-sided, 95% exact binomial confidence interval. | Transplantation through end of trial participation (up to 4.4 years post-transplant) |
| Percent of Transplant Participants Who Died | Death after receiving a kidney transplant. The endpoint is summarized with a two-sided, 95% exact binomial confidence interval. | Transplantation through end of trial participation (up to 4.4 years post-transplant) |
| Percent of Transplanted Participants With Acute Rejection or Presumed Acute Rejection | Participants with either biopsy proven acute rejection per Banff guidelines or participants that were treated for acute rejection in the absence of a biopsy. The endpoint is summarized with a two-sided, 95% exact binomial confidence interval. | Transplantation through end of trial participation (up to 4.4 years post-transplant) |
| Histological Severity of Biopsies Demonstrating Acute Rejection as Measured by Banff 2007 Grade | Biopsy-confirmed 1.) acute cellular rejection and 2.) acute antibody-mediated rejection was classified according to Banff 2007 criteria of renal allograft pathology for renal allograft rejection. A Banff result of indeterminate was not classified as rejection. Acute cellular rejection occurs when lesions at the site of the graft characteristically are infiltrated with large numbers of lymphocytes and macrophages that cause tissue damage. Acute cellular rejection is defined as a grade ≥ IA. Severity is graded as IA, IB, IIA, IIB, or III, with IA being the mildest form of cellular rejection and III being the most severe. Acute antibody-mediated rejection-or humoral rejection-is defined as a grade ≥1. Severity is graded as I, II, or III, with I being the mildest form of antibody-mediated rejection and III being the most severe. | Transplantation through end of trial participation (up to 4.4 years post-transplant) |
| Percent of Participants With Chronic T Cell-mediated or Antibody-mediated Rejection | This assessment included participants who experienced chronic T cell-mediated rejection or chronic antibody mediated rejection as well as progressive interstitial fibrosis/tubular atrophy (IF/TA), transplant glomerulopathy or chronic obliterative arteriopathy without an alternative, non-rejection-related cause. | Transplantation through end of trial participation (up to 4.4 years post-transplant) |
| Time From Transplant to the First Episode of Acute Rejection Requiring Treatment | Time (in days) from transplant to the start date of the first dose of treatment for acute rejection. This includes acute rejection episodes requiring treatment that are not biopsy proven. | Transplantation through end of trial participation (up to 4.4 years post-transplant) |
| Percent of Participants Requiring Anti-lymphocyte Therapy (OKT3, ATG) for an Acute Rejection Event | Anti-lymphocyte therapy is a drug that targets specific cells in the immune system called lymphocytes (white blood cells). This therapy helps stop the participant's immune system from attacking the donor kidney. The endpoint is summarized with a two-sided, 95% exact binomial confidence interval. | Transplantation through end of trial participation (up to 4.4 years post-transplant) |
| Number of Adverse Events, Including Number of Post-transplant Infections, Wound Complications, Lymphocoele, Post-transplant Diabetes Mellitus, and Malignancies | Adverse events that are reported as being a post-transplant infection, wound complication, lymphocoele (a collection of fluid in the lymphatic system), post-transplant diabetes mellitus or malignancy. | Transplantation through end of trial participation (up to 4.4 years post-transplant) |
| Participant Renal Function as Measured by GFR Using CKD-EPI | 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 value closest to and within 6 weeks of the day expected was selected. | 26, 52, 104, 156, and 208 Weeks Post-Transplant |
| Participant Systolic Blood Pressure Over Time | Systolic blood pressure measures the pressure on the blood vessels when the heart is beats and thus is pushing blood to the rest of the body. A normal systolic blood pressure is lower than 120 mmHg. High blood pressure, as known as hypertension, is a risk factor for coronary artery disease, stroke, heart failure, and other complications if left unmanaged. The value closest to and within 6 weeks of the day expected was selected. | 26, 52, 104, 156, and 208 Weeks Post-Transplant |
| Participant Diastolic Blood Pressure Over Time | Diastolic blood pressure measures the pressure in the arteries when the heart is at rest and is thus filled with blood. A normal diastolic blood pressure is lower than 80 mmHg. High blood pressure, as known as hypertension, is a risk factor for coronary artery disease, stroke, heart failure, and other complications if left unmanaged. The value closest to and within 6 weeks of the day expected was selected. | 26, 52, 104, 156, and 208 Weeks Post-Transplant |
| Participant Total Cholesterol Over Time | Total cholesterol measures the amount of cholesterol found in the blood. Cholesterol is a waxy substance your body needs to build cells, but too much can be a problem since it can build-up in arteries. Narrowed arteries can result in heart attack or stroke. A value less than 200 mg/dL is considered good. The value closest to and within 12 weeks of the day expected was selected. | 26, 52, 104, 156, and 208 Weeks Post-Transplant |
| Participant Glucose Level Over Time | This is a measure of glucose found in the blood. Glucose, a sugar, is an energy source that the body relies on to properly function. If levels are too high for a long period of time, diabetes can develop. Diabetes can result in many long-term complications such as eye, kidney, and nerve damage, stroke, and cardiovascular complications. Fasting levels for glucose should be around 70-99 mg/dL and less than 140 mg/dL within 2 hours after a meal. The value closest to and within 6 weeks of the day expected was selected. | 26, 52, 104, 156, and 208 Weeks Post-Transplant |
| University of Maryland Medical Center |
| Baltimore |
| Maryland |
| 21201 |
| United States |
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| Rogosin Institute/New York Presbyterian-Cornell | New York | New York | 10021 | United States |
| Hospital at the University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| University of Wisconsin | Madison | Wisconsin | 53792 | United States |
| Division of Allergy, Immunology, and Transplantation (DAIT) | View source |
| Immune Tolerance Network (ITN) | View source |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Serum Creatinine | Serum creatinine provides an estimate of how well the kidneys filter (glomerular filtration rate). Higher results= poorer kidney function. The baseline creatinine interval per protocol is defined as the 2 to 4 week interval post-kidney transplant and is calculated using the lowest N=3 serum creatinine values during this pre-defined interval, the interval prior to immunosuppressive maintenance withdrawal (IMW) initiation. Normal values: Adult males, 0.7 to 1.3 mg/dL; adult females, 0.6 to 1.1 mg/dL. | Mean | Standard Deviation | mg/dL |
|
| eGFR | Glomerular filtration rate (GFR) is a measure of kidney function and helps determine the stage of kidney disease. The equation developed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) is used to estimate GFR (e.g., eGFR) from serum creatinine. Baseline serum creatinine was used in the equation, which is the average of the lowest three creatinine values during 2 to 4 weeks post-transplant, excluding days on dialysis. | Mean | Standard Deviation | mg/dL |
|
| Systolic Blood Pressure | The systolic blood pressure collected on the day of transplant. If there is no value recorded on the day of transplant, the value from the screening visit is used. Systolic blood pressure measures the pressure on the blood vessels when the heart is beats and thus is pushing blood to the rest of the body. A normal systolic blood pressure is lower than 120 mmHg. High blood pressure, also known as hypertension, is a risk factor for coronary artery disease, stroke, heart failure, and other complications if left unmanaged. | Mean | Standard Deviation | mmHg |
|
| Diastolic Blood Pressure | The diastolic blood pressure collected on the day of transplant. If there is no value recorded on the day of transplant, the value from the screening visit is used. Diastolic blood pressure measures the pressure in the arteries when the heart is at rest and is thus filled with blood. A normal diastolic blood pressure is lower than 80 mmHg. High blood pressure, as known as hypertension, is a risk factor for coronary artery disease, stroke, heart failure, and other complications if left unmanaged. | Mean | Standard Deviation | mmHg |
|
| Total Cholesterol | The total cholesterol collected on the day of transplant. If there is no value recorded on the day of transplant, the value from the screening visit is used. Total cholesterol measures the amount of cholesterol found in the blood. Cholesterol is a waxy substance your body needs to build cells, but too much can be a problem since it can build-up in arteries. Narrowed arteries can result in heart attack or stroke. A value less than 200 mg/dL is considered good. | Mean | Standard Deviation | mg/dL |
|
| Glucose | The glucose collected on the day of transplant. If there is no value recorded on the day of transplant, the value from the screening visit is used. Glucose, a sugar, is an energy source that the body relies on to properly function. If levels are too high for a long period of time, diabetes can develop. Diabetes can result in many long-term complications such as eye, kidney, and nerve damage, stroke, and cardiovascular complications. Fasting levels for glucose should be around 70-99 mg/dL and less than 140 mg/dL within 2 hours after a meal. | Mean | Standard Deviation | mg/dL |
|
Adult living donor kidney transplant recipients were enrolled into the study prior to transplant. Participants received a novel induction regimen of ATG and rituximab that included 4 doses of ATG 1.5 mg/kg and 2 doses of rituximab 375 mg/m^2. The first dose of rituximab was given ~ day -6 pre-transplant, and the second dose on day 1-3 post-transplant. The first dose of ATG was given on the day of transplant, with the additional three doses administered on days 2-7 post-transplant (not on the same day as rituximab). Participants were maintained on anti-rejection medications tacrolimus, MMF, and sirolimus post-transplant. Participants were evaluated for eligibility to proceed with immunosuppressive maintenance withdrawal (IMW), a gradual withdrawal of their anti-rejection medications, starting as early as 26 weeks post-transplant. IMW for eligible participants proceeded with close monitoring per protocol over a period of 68-104 weeks. |
|
|
| Secondary | Percent of Transplanted Participants Who Remain Off Immunosuppression for at Least 52 Weeks Including Those in Whom the 52 Week Biopsy Was Not Performed | Participants are considered successfully withdrawn from immunosuppression if they remained off immunosuppression for at least 52 weeks without evidence of rejection. A biopsy performed 52 weeks after completion of immunosuppression withdrawal confirmed that there was no sub-clinical evidence of rejection. This result considers a participant off all immunosuppression for at least 52 weeks with or without the confirmatory week 52 biopsy as a success. The endpoint is summarized with a two-sided, 95% exact binomial confidence interval. | Participants that received induction (Rituximab and ATG) and were transplanted on study | Posted | Number | 95% Confidence Interval | Percent of participants | Transplantation through 52 weeks after discontinuation of all immunosuppression |
|
|
|
| Secondary | Percent of Transplanted Participants Who Remain Off Immunosuppression for the Duration of the Study as Defined as Completion of All Schedules of Events/Followed Through August 25, 2017 | Participants that remained off all immunosuppression through the completion of study participation. The endpoint is summarized with a two-sided, 95% exact binomial confidence interval. | Participants that received induction (Rituximab and ATG) and were transplanted on study | Posted | Number | 95% Confidence Interval | Percent of participants | Transplantation through study completion (up to 4.4 years post-transplant) |
|
|
|
| Secondary | Percent of Transplanted Participants Who Achieve Sirolimus Monotherapy Within 52 Weeks Post-transplant | Participants that were treated with only sirolimus within 52 weeks after transplantation in those who could tolerant sirolimus. The endpoint is summarized with a two-sided, 95% exact binomial confidence interval. | Participants that received induction (Rituximab and ATG) and were transplanted on study that tolerated sirolimus | Posted | Number | 95% Confidence Interval | Percent of participants | Transplantation through 52 weeks post-transplantation |
|
|
|
| Secondary | Percent of Transplanted Participants Who Achieve MMF or Mycophenolic Acid Monotherapy Within 52 Weeks Post-transplant in Those Participants Intolerant of Sirolimus | Participants that were treated with only mycophenolate mofetil (MMF) or mycophenolic acid within 52 weeks after transplantation in those who could not tolerate sirolimus. The endpoint is summarized with a two-sided, 95% exact binomial confidence interval. | Participants that received induction (Rituximab and ATG) and were transplanted on study that could not tolerate sirolimus | Posted | Number | 95% Confidence Interval | Percent of participants | Transplantation through 52 weeks post-transplantation |
|
|
|
| Secondary | Percent of Transplanted Participants Who Achieve Either Sirolimus Monotherapy or Monotherapy on a Mycophenolic Compound Within 52 Weeks Post-transplant | Participants that were treated with only sirolimus or treated with only mycophenolate mofetil (MMF) or mycophenolic acid within 52 weeks after transplantation. The endpoint is summarized with a two-sided, 95% exact binomial confidence interval. | Participants that received induction (Rituximab and ATG) and were transplanted on study | Posted | Number | 95% Confidence Interval | Percent of participants | Transplantation through 52 weeks post-transplantation |
|
|
|
| Secondary | Immunosuppression-free Duration in Days, Defined as Time From Completion of Immunosuppression Withdrawal to End of Trial Participation or to Time of Restarting Immunosuppression | Time (in days) from when the participant is off all immunosuppression to the end of trial participation or re-initiation of immunosuppression, whichever is earliest. | Participants that received induction (Rituximab and ATG) and were transplanted on study that stopped using all immunosuppression drugs | Posted | Median | Inter-Quartile Range | Days | Transplantation through end of trial participation (up to 4.4 years post-transplant) |
|
|
|
| Secondary | Time From Completion of Immunosuppression Withdrawal to First Episode of Acute Rejection or Presumed Acute Rejection | Time (in days) from when the participant is off all immunosuppression to the first episode of biopsy proven or presumed acute rejection. | Participants that received induction (Rituximab and ATG) and were transplanted on study that stopped using all immunosuppression drugs and had acute rejection or presumed acute rejection. | Posted | Median | Inter-Quartile Range | Days | Transplantation through end of trial participation (up to 4.4 years post-transplant) |
|
|
|
| Secondary | Time From Completion of Immunosuppression Withdrawal to First Diagnosis of Chronic T Cell Mediated or Antibody-mediated Rejection | Time (in days) from the time the participant is off all immunosuppression to the first episode of chronic T cell mediated or chronic antibody-mediated rejection. This assessment also includes progressive interstitial fibrosis/tubular atrophy (IF/TA), transplant glomerulopathy or chronic obliterative arteriopathy without an alternative, non-rejection related cause. | Participants that received induction (Rituximab and ATG) and were transplanted on study that stopped using all immunosuppression drugs and were diagnosed with chronic rejection. | Posted | Transplantation through end of trial participation (up to 4.4 years post-transplant) |
|
|
| Secondary | Percent of Transplanted Participants With Graft Loss | A participant is considered to have graft loss when the donated kidney needs to be removed, the participant is retransplanted with another donor kidney, or chronic dialysis is instituted. The endpoint is summarized with a two-sided, 95% exact binomial confidence interval. | Participants that received induction (Rituximab and ATG) and were transplanted on study. | Posted | Number | 95% Confidence Interval | Percent of participants | Transplantation through end of trial participation (up to 4.4 years post-transplant) |
|
|
|
| Secondary | Percent of Transplant Participants Who Died | Death after receiving a kidney transplant. The endpoint is summarized with a two-sided, 95% exact binomial confidence interval. | Participants that received induction (Rituximab and ATG) and were transplanted on study | Posted | Number | 95% Confidence Interval | Percent of participants | Transplantation through end of trial participation (up to 4.4 years post-transplant) |
|
|
|
| Secondary | Percent of Transplanted Participants With Acute Rejection or Presumed Acute Rejection | Participants with either biopsy proven acute rejection per Banff guidelines or participants that were treated for acute rejection in the absence of a biopsy. The endpoint is summarized with a two-sided, 95% exact binomial confidence interval. | Participants that received induction (Rituximab and ATG) and were transplanted on study. | Posted | Geometric Least Squares Mean | 95% Confidence Interval | Percent of participants | Transplantation through end of trial participation (up to 4.4 years post-transplant) |
|
|
|
| Secondary | Histological Severity of Biopsies Demonstrating Acute Rejection as Measured by Banff 2007 Grade | Biopsy-confirmed 1.) acute cellular rejection and 2.) acute antibody-mediated rejection was classified according to Banff 2007 criteria of renal allograft pathology for renal allograft rejection. A Banff result of indeterminate was not classified as rejection. Acute cellular rejection occurs when lesions at the site of the graft characteristically are infiltrated with large numbers of lymphocytes and macrophages that cause tissue damage. Acute cellular rejection is defined as a grade ≥ IA. Severity is graded as IA, IB, IIA, IIB, or III, with IA being the mildest form of cellular rejection and III being the most severe. Acute antibody-mediated rejection-or humoral rejection-is defined as a grade ≥1. Severity is graded as I, II, or III, with I being the mildest form of antibody-mediated rejection and III being the most severe. | Participants that received induction (Rituximab and ATG) and were transplanted on study. | Posted | Number | Biopsies | Transplantation through end of trial participation (up to 4.4 years post-transplant) |
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|
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| Secondary | Percent of Participants With Chronic T Cell-mediated or Antibody-mediated Rejection | This assessment included participants who experienced chronic T cell-mediated rejection or chronic antibody mediated rejection as well as progressive interstitial fibrosis/tubular atrophy (IF/TA), transplant glomerulopathy or chronic obliterative arteriopathy without an alternative, non-rejection-related cause. | Participants that received induction (Rituximab and ATG) and were transplanted on study. | Posted | Number | 95% Confidence Interval | Percent of participants | Transplantation through end of trial participation (up to 4.4 years post-transplant) |
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|
| Secondary | Time From Transplant to the First Episode of Acute Rejection Requiring Treatment | Time (in days) from transplant to the start date of the first dose of treatment for acute rejection. This includes acute rejection episodes requiring treatment that are not biopsy proven. | Participants that received induction (Rituximab and ATG) and were transplanted on study that had acute rejection requiring treatment. | Posted | Median | Inter-Quartile Range | Days | Transplantation through end of trial participation (up to 4.4 years post-transplant) |
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| Secondary | Percent of Participants Requiring Anti-lymphocyte Therapy (OKT3, ATG) for an Acute Rejection Event | Anti-lymphocyte therapy is a drug that targets specific cells in the immune system called lymphocytes (white blood cells). This therapy helps stop the participant's immune system from attacking the donor kidney. The endpoint is summarized with a two-sided, 95% exact binomial confidence interval. | Participants that received induction (Rituximab and ATG) and were transplanted on study. | Posted | Number | 95% Confidence Interval | Percent of participants | Transplantation through end of trial participation (up to 4.4 years post-transplant) |
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| Secondary | Number of Adverse Events, Including Number of Post-transplant Infections, Wound Complications, Lymphocoele, Post-transplant Diabetes Mellitus, and Malignancies | Adverse events that are reported as being a post-transplant infection, wound complication, lymphocoele (a collection of fluid in the lymphatic system), post-transplant diabetes mellitus or malignancy. | Participants that received induction (Rituximab and ATG) and were transplanted on study | Posted | Number | Events | Transplantation through end of trial participation (up to 4.4 years post-transplant) |
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| Secondary | Participant Renal Function as Measured by GFR Using CKD-EPI | 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 value closest to and within 6 weeks of the day expected was selected. | Participants that received induction (Rituximab and ATG) and were transplanted on study, with data available at each time point. | Posted | Median | Inter-Quartile Range | mL/min/1.73m^2 | 26, 52, 104, 156, and 208 Weeks Post-Transplant |
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| Secondary | Participant Systolic Blood Pressure Over Time | Systolic blood pressure measures the pressure on the blood vessels when the heart is beats and thus is pushing blood to the rest of the body. A normal systolic blood pressure is lower than 120 mmHg. High blood pressure, as known as hypertension, is a risk factor for coronary artery disease, stroke, heart failure, and other complications if left unmanaged. The value closest to and within 6 weeks of the day expected was selected. | Participants that received induction (Rituximab and ATG) and were transplanted on study, with data available at each time point. | Posted | Median | Inter-Quartile Range | mmHg | 26, 52, 104, 156, and 208 Weeks Post-Transplant |
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| Secondary | Participant Diastolic Blood Pressure Over Time | Diastolic blood pressure measures the pressure in the arteries when the heart is at rest and is thus filled with blood. A normal diastolic blood pressure is lower than 80 mmHg. High blood pressure, as known as hypertension, is a risk factor for coronary artery disease, stroke, heart failure, and other complications if left unmanaged. The value closest to and within 6 weeks of the day expected was selected. | Participants that received induction (Rituximab and ATG) and were transplanted on study, with data available at each time point. | Posted | Median | Inter-Quartile Range | mmHg | 26, 52, 104, 156, and 208 Weeks Post-Transplant |
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| Secondary | Participant Total Cholesterol Over Time | Total cholesterol measures the amount of cholesterol found in the blood. Cholesterol is a waxy substance your body needs to build cells, but too much can be a problem since it can build-up in arteries. Narrowed arteries can result in heart attack or stroke. A value less than 200 mg/dL is considered good. The value closest to and within 12 weeks of the day expected was selected. | Participants that received induction (Rituximab and ATG) and were transplanted on study, with data available at each time point. | Posted | Median | Inter-Quartile Range | mg/dL | 26, 52, 104, 156, and 208 Weeks Post-Transplant |
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| Secondary | Participant Glucose Level Over Time | This is a measure of glucose found in the blood. Glucose, a sugar, is an energy source that the body relies on to properly function. If levels are too high for a long period of time, diabetes can develop. Diabetes can result in many long-term complications such as eye, kidney, and nerve damage, stroke, and cardiovascular complications. Fasting levels for glucose should be around 70-99 mg/dL and less than 140 mg/dL within 2 hours after a meal. The value closest to and within 6 weeks of the day expected was selected. | Participants that received induction (Rituximab and ATG) and were transplanted on study, with data available at each time point. | Posted | Median | Inter-Quartile Range | mg/dL | 26, 52, 104, 156, and 208 Weeks Post-Transplant |
|
|
|
| 7 |
| 10 |
| 10 |
| 10 |
| Transplant rejection | Immune system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pyelonephritis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Incisional hernia | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
|
| Seroma | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
|
| Toxicity to various agents | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
|
| Cerebrovascular accident | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Nephrolithiasis | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Renal injury | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Aortic valve incompetence | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hyperparathyroidism secondary | Endocrine disorders | MedDRA 14.0 | Systematic Assessment |
|
| Mouth ulceration | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Transplant rejection | Immune system disorders | MedDRA 14.0 | Systematic Assessment |
|
| BK virus infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Cytomegalovirus viraemia | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Viraemia | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 14.0 | Systematic Assessment |
|
| Eosinophil count increased | Investigations | MedDRA 14.0 | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | MedDRA 14.0 | Systematic Assessment |
|
| Transaminases increased | Investigations | MedDRA 14.0 | Systematic Assessment |
|
| White blood cell count decreased | Investigations | 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 |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| IgA nephropathy | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Nephropathy | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
|
| Varicose vein | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
|
| Venous insufficiency | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
|
Not provided
Not provided
| D001798 |
| Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D002208 | Caproates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| Title | Measurements |
|---|---|
|
| Acute Cellular Rejection (Type IIB) |
|
| Acute Cellular Rejection (Type III) |
|
| Acute Antibody-Mediated Rejection (Type I) |
|
| Acute Antibody-Mediated Rejection (Type II) |
|
| Acute Antibody-Mediated Rejection (Type III) |
|
| Title | Measurements |
|---|---|
|
| Post-Transplant Diabetes Mellitus |
|
| Malignancy |
|
|
| 104 Weeks Post-Transplant |
|
|
| 156 Weeks Post-Transplant |
|
|
| 208 Weeks Post-Transplant |
|
|
|
| 104 Weeks Post-Transplant |
|
|
| 156 Weeks Post-Transplant |
|
|
| 208 Weeks Post-Transplant |
|
|
|
| 104 Weeks Post-Transplant |
|
|
| 156 Weeks Post-Transplant |
|
|
| 208 Weeks Post-Transplant |
|
|
|
| 104 Weeks Post-Transplant |
|
|
| 156 Weeks Post-Transplant |
|
|
| 208 Weeks Post-Transplant |
|
|
|
| 104 Weeks Post-Transplant |
|
|
| 156 Weeks Post-Transplant |
|
|
| 208 Weeks Post-Transplant |
|
|