Tacrolimus to Sirolimus Conversion for Delayed Graft Function (RAPA)
Recruitment status was: Recruiting
|Kidney Transplant Delayed Graft Function Slow Graft Function-defined at Creatinine >= 3.0 by Post-op Day 5 Without Requiring Dialysis||Drug: Tacrolimus (FK506, Prograf) Drug: Sirolimus (Rapamune, Rapamycin)||Phase 4|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Delayed Tacrolimus to Sirolimus Conversion in Renal Transplant Recipients With Delayed Graft Function|
- The composite endpoint of reduction of e eGFR at one year by more than 15% & the progression in fibrosis score at one year by >=20% compared with the baseline values [ Time Frame: One year ]
- eGFR [ Time Frame: One year ]
- Change in eGFR from baseline to 1-year [ Time Frame: 1 year ]
- Graft survival (Actual, Actuarial) [ Time Frame: 1 year; up to 3 years ]
- Patient survival (Actual and Actuarial) [ Time Frame: 1-year; up to 3 years ]
- Incidence & severity of acute rejection (Actual, Actuarial) [ Time Frame: 1 year; up to 3 years ]
- Incidence of development of DSA [ Time Frame: Up to 3 years ]
- Incidence of BK nephropathy (Cumulative) [ Time Frame: Up to 3 years ]
- Change in inflammatory markers (including IL-6, MCP, CRP)from baseline [ Time Frame: 1 year ]
|Study Start Date:||April 2009|
|Estimated Study Completion Date:||February 2012|
|Estimated Primary Completion Date:||November 2011 (Final data collection date for primary outcome measure)|
Active Comparator: Tacrolimus
Tacrolimus will be continued with target 12-hour trough level 7-10 ng/ml (tandem mass spectrometry) during the first year and 5-8 during second year.
Drug: Tacrolimus (FK506, Prograf)
3-10 mg, PO, BID based on 12 hour trough on serum blood levels, adjusted according to protocol
Other Name: FK506, Prograf
Active Comparator: Sirolimus
5 mg, PO , daily
Drug: Sirolimus (Rapamune, Rapamycin)
5 mg, PO, daily based on 24 hour serum blood levels, adjusted according to protocol
Eligible study subjects will be randomized into two groups 8-18 weeks after surgery. One group will be maintained on tacrolimus according to the standard of care at our center. In the second group tacrolimus will be converted to sirolimus, with one week overlap between sirolimus therapy and tacrolimus taper. All the deceased donor kidney transplant recipients transplanted at our center who experience DGF/SGF are eligible for inclusion in this study, if they meet the inclusion/exclusion criteria as detailed later.
Data will be collected on patient demographics, duration on dialysis, history of diabetes and chronic hepatitis C, previous transplantation, PRA, donor source, warm and cold ischemia time, donor demographics and comorbidity such as diabetes and hypertension, serum creatinine at the time of organ removal, early graft function, number of dialysis treatments after transplantation, induction agent and immunosuppressive regimen including the dose or level of the drugs at 3, 6, 9, 12, 18, and 24 months. Similar data regarding use of ACE inhibitors/ARBs, erythropoietic agents, number of anti-hypertensives and lipid lowering agents will be collected. In addition, the following tests and procedures will be obtained for this study.
- GFR measurement by cold iothalamate method at one year after transplantation.
- Evaluation of routine surveillance graft biopsies for chronic changes at 3 and 12 months posttransplant by morphometric analysis.
- Spot urine protein, albumin, and creatinine measurement at 3 and 12 months.
- Estimate GFR at 3, and 12 months using MDRD, CG, and Nankivell formulas
- Examine the surveillance and indicated biopsies for acute rejection and BK nephropathy.
- Fasting lipid profile at 3 and 12 months for all patients, and 24 months for those with at least 2 years of follow up.
- Office blood pressure measurements at 3 and 12 months for all patients, and 24 months for those with at least 2 years of follow up.
- Measurement of CRP, IL-6, and MCP at 3 and 12 months.
The safety measures will include:
Incidence of leukopenia (WBC < 3000) or thrombocytopenia (PLT < 100,000); hemoglobin level at 12 months; proteinuria at 12 months; incidence of oral aphthous ulcers; incidence of new onset diabetes, incidence of CMV infection and rate of drug withdrawal due to side effects.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00931255
|Contact: Abdolreza Haririan, MD, MPHfirstname.lastname@example.org|
|Contact: Caroline Pancotti, RNemail@example.com|
|United States, Maryland|
|University of Maryland Medical Center||Recruiting|
|Baltimore, Maryland, United States, 21201|
|Contact: Caroline Pancotti, RN 410-328-5720 firstname.lastname@example.org|
|Contact: Hongxia Li 410-328-0206 email@example.com|
|Sub-Investigator: David Klassen, MD|
|Sub-Investigator: Matthew Cooper, MD|
|Principal Investigator:||Abdolreza Haririan, MD, MPH||University of Maryland|