Low Dose Thymoglobin in Renal Transplant Patients
Condition: Acute Renal Failure
MeSH terms: Acute Kidney Injury
Study type: Interventional

Summary: 
      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 description: 
      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:

        1. Type of renal transplant (living vs cadaveric)

        2. HLA matching

        3. CMV status of donor and recipient

        4. EBV status of donor and recipient

        5. Creatinine prior to transplantation

        6. Urinalysis at the time of transplantation

        7. Primary renal disease

        8. Weight of the renal transplant

        9. BMI of the recipient and donor

       10. Age of the donor and recipient

       11. Sex of the donor and recipient

       12. White blood cell count

       13. Hemoglobin

       14. Platelets

       15. History of infections

       16. History of malignancies

      During each of the clinic visits the investigators will obtain the following information:

        1. Creatinine

        2. Urinalysis

        3. White blood cell count

        4. Hemoglobin

        5. Platelets

        6. Weight of the recipient

        7. Infections

        8. Malignancies

        9. 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.
    

Intervention name(s): Thymoglobulin; Thymoglobulin 0.75mg/kg dose
Intervention type(s): Drug; Drug
Intervention description(s): Thymoglobulin 1.25mg/kg dose; Thymoglobulin
Other intervention name(s): Thymoglobulin
Intervention MeSH terms: Thymoglobulin; Antilymphocyte Serum
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Renal Transplant; Thymoglubulin