Low Dose Thymoglobin in Renal Transplant Patients
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Low Dose Thymoglobulin As Induction Agent on Prednisone-Free Regimens of Renal Transplant Recipients|
- Evaluate the rates of acute cellular rejection between study groups [ Time Frame: 1 year ]Data from study participants will be collected for up to 1 year post-transplant.
- Evaluate the rates of infections, leucopenia and malignacy between study groups [ Time Frame: 1 year ]Data from study participants will be collected for up to 1 year post-transplant.
|Study Start Date:||October 2010|
|Study Completion Date:||January 2014|
|Primary Completion Date:||November 2013 (Final data collection date for primary outcome measure)|
Experimental: 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 1.25mg/kg dose
Experimental: Thymoglobulin 0.75mg/kg dose
The safety and efficacy of low dose Thymoglobulin (0.75mg/kg) as an induction agent in renal transplant subjects.
Drug: Thymoglobulin 0.75mg/kg dose
Other Name: Thymoglobulin
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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:
- Type of renal transplant (living vs cadaveric)
- HLA matching
- CMV status of donor and recipient
- EBV status of donor and recipient
- Creatinine prior to transplantation
- Urinalysis at the time of transplantation
- Primary renal disease
- Weight of the renal transplant
- BMI of the recipient and donor
- Age of the donor and recipient
- Sex of the donor and recipient
- White blood cell count
- History of infections
- History of malignancies
During each of the clinic visits the investigators will obtain the following information:
- White blood cell count
- Weight of the recipient
- Renal biopsy report if a biopsy was performed
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01280617
|United States, Massachusetts|
|Burlington, Massachusetts, United States, 01805|
|Principal Investigator:||Hannah M. Gilligan, MD||Lahey Clinic|