Low Dose Thymoglobin in Renal Transplant Patients

Tracking Information
First Submitted Date ICMJE	January 19, 2011
First Posted Date ICMJE	January 21, 2011
Last Update Posted Date	May 29, 2014
Study Start Date ICMJE	October 2010
Actual Primary Completion Date	November 2013 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: January 20, 2011)	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.
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01280617 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: January 20, 2011)	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.
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Low Dose Thymoglobin in Renal Transplant Patients
Official Title ICMJE	Low Dose Thymoglobulin As Induction Agent on Prednisone-Free Regimens of Renal Transplant Recipients
Brief 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: 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; Hemoglobin; Platelets; History of infections; History of malignancies During each of the clinic visits the investigators will obtain the following information: Creatinine; Urinalysis; White blood cell count; Hemoglobin; Platelets; Weight of the recipient; Infections; Malignancies; 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.
Study Type ICMJE	Interventional
Study Phase	Not Applicable
Study Design ICMJE	Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Acute Renal Failure
Intervention ICMJE	Drug: Thymoglobulin Thymoglobulin 1.25mg/kg dose; Drug: Thymoglobulin 0.75mg/kg dose Thymoglobulin Other Name: Thymoglobulin
Study Arms	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. Intervention: Drug: Thymoglobulin; 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. Intervention: Drug: Thymoglobulin 0.75mg/kg dose
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: May 28, 2014)	58
Original Estimated Enrollment ICMJE; (submitted: January 20, 2011)	100
Actual Study Completion Date	January 2014
Actual Primary Completion Date	November 2013 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Potential Adult Renal Transplant Patients - Exclusion Criteria: Sensitized Renal Transplant Patients
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 80 Years (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01280617
Other Study ID Numbers ICMJE	2010-065
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Lahey Clinic
Study Sponsor ICMJE	Lahey Clinic
Collaborators ICMJE	Brigham and Women's Hospital
Investigators ICMJE	Principal Investigator: Hannah M. Gilligan, MD Lahey Clinic
PRS Account	Lahey Clinic
Verification Date	May 2014
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP