Clinical trial NCT00931255
Conditions: Kidney Transplant Delayed Graft Function
Keywords: kidney transplant tacrolimus sirolimus delayed graft function Graft survival Acute rejection Chronic allograft nephropathy
Sponsor: University of Maryland, Baltimore
Start date: 2009-04-01; Completion date: 2014-07-01
Enrollment: 32 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The objective of this study is to evaluate the safety and efficacy of conversion from tacrolimus to sirolimus early after kidney transplantation in patients with delayed graft function (DGF)and slow graft function (SGF) in improving graft function and delaying chronic allograft nephropathy. The investigators hypothesize that conversion from tacrolimus to sirolimus in renal transplant recipients with DGF/SGF in early months after surgery will improve graft function and decrease the progression of graft fibrosis.

Detailed description:
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.

1. GFR measurement by cold iothalamate method at one year after transplantation.
2. Evaluation of routine surveillance graft biopsies for chronic changes at 3 and 12 months posttransplant by morphometric analysis.
3. Spot urine protein, albumin, and creatinine measurement at 3 and 12 months.
4. Estimate GFR at 3, and 12 months using MDRD, CG, and Nankivell formulas
5. Examine the surveillance and indicated biopsies for acute rejection and BK nephropathy.
6. Fasting lipid profile at 3 and 12 months for all patients, and 24 months for those with at least 2 years of follow up.
7. 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.
8. 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.

Arms: arm 1: 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. arm 2: 5 mg, PO , daily
Interventions: intervention 1: Tacrolimus intervention 2: Sirolimus
Intervention descriptions: intervention 1: 3-10 mg, PO, BID based on 12 hour trough on serum blood levels, adjusted according to protocol intervention 2: 5 mg, PO, daily based on 24 hour serum blood levels, adjusted according to protocol

Protocol documents: