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| Name | Class |
|---|---|
| Brigham and Women's Hospital | OTHER |
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This is a planned single center prospective randomized study evaluating the safety and efficacy of low dose thymoglobulin as induction agent in renal transplant recipients. Inclusion criteria will be adult renal transplant recipients who are not sensitized against their potential donors. The patients who agree to participate in the study will be randomly assigned to either thymoglobulin at 1.25mg/kg x 3 doses or 0.75mg/kg x 3 doses. There will be 86 sealed envelopes to perform the randomization process. 43 envelopes with 1.25mg/kg dosing and the other 43 envelopes with 0.75mg/kg dosing. The investigators will sequentially choose the sealed envelopes at the time of the patient randomization process. All patients will be started on our standard immunosupression regimen of prograf/cellcept and a fast steroid taper. Data will be obtained from every patient for up to one year post-transplant.
Detailed Study Design:
This is a planned single center prospective randomized study evaluating the safety and efficacy of low dose thymoglobulin as induction agent in renal transplant recipients. Inclusion criteria will be adult renal transplant recipients who are not sensitized against their potential donors. The patients who agree to participate in the study will be randomly assigned to either thymoglobulin at 1.25mg/kg x 3 doses or 0.75mg/kg x 3 doses. There will be 86 sealed envelopes to perform the randomization process. 43 envelopes with 1.25mg/kg dosing and the other 43 envelopes with 0.75mg/kg dosing. The investigators will sequentially choose the sealed envelopes at the time of the patient randomization process. All patients will be started on our standard immunosupression regimen of prograf/cellcept and a fast steroid taper. Data will be obtained from every patient for up to one year post-transplant.
The investigators will obtain the following information at the time of consent:
During each of the clinic visits the investigators will obtain the following information:
In addition to the standard of care laboratories, the investigators will ask patients to give us 7 additional green tubes, one purple tube and two red tubes which will be drawn at the time of standard of care laboratories pre-transplantation, 3 months post-transplant, 6 months post-transplant and 12 months post-transplant. This tubes will be used to measure CD4, CD8, CD19, CD20, CD68 cells as these are cells that are believed to be affected by the use of thymoglobulin.
If the patient is to have a renal transplant biopsy at any time during the 12 months of the study, any excess tissue may be utilized for staining of special cell markers including CD4, CD8, CD19, CD20 and CD68.
Subject inclusion criteria: Potential adult renal transplant recipients
Subject exclusion criteria: Sensitized renal transplant recipients
Methods of statistical analysis to be employed in preparation of reports:
The investigators are planning a study with 1 control per experimental subject, an accrual interval of 24 time units, and additional follow-up after the accrual interval of 12 time units. In a previous study the median survival time on the control treatment was 36 time units. If the true hazard ratio (relative risk) of control subjects relative to experimental subjects is 5, the investigators will need to study 43 experimental subjects and 43 control subjects to be able to reject the null hypothesis that the experimental and control survival curves are equal with probability (power) .800. The Type I error probability associated with this test of this null hypothesis is 0.05. T-tests will be used to compare both groups.
Thymoglobulin (rabbit antithymocyte globulin) is FDA approved for the treatment of acute cellular rejection. Nevertheless, for at least the past 10 years this medication has been utilized as induction agent in renal transplant recipients. This is because an induction agent allows prednisone withdrawal in renal transplant recipients.
Prednisone withdrawal is extremely important in renal transplant recipients as old protocols that allowed long term prednisone use compromised the long term health of renal transplant recipients. Not only does prednisone increase markedly the risk of development of diabetes and osteoporosis, but is also increases drastically the risk of fractures, which is a very common cause of mortality in long term prednisone renal transplant recipients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Thymoglobulin 1.25mg/kg dose | Experimental | The safety and efficacy of low dose Thymoglobulin (1.25mg/kg) as an induction agent in renal transplant subjects. |
|
| Thymoglobulin 0.75mg/kg dose | Experimental | The safety and efficacy of low dose Thymoglobulin (0.75mg/kg) as an induction agent in renal transplant subjects. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Thymoglobulin | Drug | Thymoglobulin 1.25mg/kg dose |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Rates of Acute Cellular Rejection Between Study Group | Incidence of Biopsy Proven Acute Rejection at 1 year post transplant: | 1 year from date of transplant |
| Measure | Description | Time Frame |
|---|---|---|
| , "Total Number of Adverse Events, Including Any Infections, Leucopenia, and Malignancy" | Number of individual adverse events in high versus low dose Thymoglobulin groups will be tabulated and statistical analyses performed | 1 year from date of transplant |
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Inclusion Criteria:
Potential Adult Renal Transplant Patients -
Exclusion Criteria:
Sensitized Renal Transplant Patients
-
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| Name | Affiliation | Role |
|---|---|---|
| Simpson | Lahey Hospital & Medical Ctr | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Lahey Clinic | Burlington | Massachusetts | 01805 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25111080 | Result | Grafals M, Smith B, Murakami N, Trabucco A, Hamill K, Marangos E, Gilligan H, Pomfret EA, Pomposelli JJ, Simpson MA, Azzi J, Najafian N, Riella LV. Immunophenotyping and efficacy of low dose ATG in non-sensitized kidney recipients undergoing early steroid withdrawal: a randomized pilot study. PLoS One. 2014 Aug 11;9(8):e104408. doi: 10.1371/journal.pone.0104408. eCollection 2014. |
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All unsensitized renal transplant recipients were considered eligible and were approached for consent. Inclusion dates were October 2010 until April 2013. A total of 58 patients were approached; 44 consented and were enrolled in the protocol
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| ID | Title | Description |
|---|---|---|
| FG000 | Thymoglobulin 1.25mg/kg Dose | The safety and efficacy of low dose Thymoglobulin (1.25mg/kg) as an induction agent in renal transplant subjects. Thymoglobulin: Thymoglobulin 1.25mg/kg dose |
| FG001 | Thymoglobulin 0.75mg/kg Dose | The safety and efficacy of low dose Thymoglobulin (0.75mg/kg) as an induction agent in renal transplant subjects. Thymoglobulin 0.75mg/kg dose: Thymoglobulin |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Thymoglobulin 1.25mg/kg Dose | The safety and efficacy of low dose Thymoglobulin (1.25mg/kg) as an induction agent in renal transplant subjects. Thymoglobulin: Thymoglobulin 1.25mg/kg dose |
| BG001 | Thymoglobulin 0.75mg/kg Dose |
| 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 | Rates of Acute Cellular Rejection Between Study Group | Incidence of Biopsy Proven Acute Rejection at 1 year post transplant: | Posted | Number | Number of rejection | 1 year from date of transplant |
|
Day of kidney transplant until end of first post transplant year
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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 | Thymoglobulin 1.25mg/kg Dose | Thymoglobulin 1.25mg/kg dose All Cause mortality 0/23 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Serious Infections | Infections and infestations | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Delayed Graft Function | Renal and urinary disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mary Ann Simpson, Ph.D | Lahey Hospital & Medical Ctr | 781-744-2500 | Mary.a.Simpson@Lahey.org |
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| ID | Term |
|---|---|
| D058186 | Acute Kidney Injury |
| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
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| ID | Term |
|---|---|
| C512542 | thymoglobulin |
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| Thymoglobulin 0.75mg/kg dose |
| Drug |
Thymoglobulin |
|
|
The safety and efficacy of low dose Thymoglobulin (0.75mg/kg) as an induction agent in renal transplant subjects.
Thymoglobulin 0.75mg/kg dose: Thymoglobulin
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex/Gender, Customized | Count of Participants | Participants |
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
|
| Secondary | , "Total Number of Adverse Events, Including Any Infections, Leucopenia, and Malignancy" | Number of individual adverse events in high versus low dose Thymoglobulin groups will be tabulated and statistical analyses performed | Posted | Number | Adverse Events | 1 year from date of transplant |
|
|
|
| 0 |
| 23 |
| 3 |
| 23 |
| 3 |
| 23 |
| EG001 | Thymoglobulin 0.75mg/kg Dose | Thymoglobulin 0.75mg/kg dose All Cause Mortality 3/20 - 2 with pre-existing cardiac disease, diabetes, and history of smoking | 3 | 20 | 2 | 20 | 8 | 20 |
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| D005261 |
| Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |