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Tacrolimus to Sirolimus Conversion for Delayed Graft Function (RAPA)

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ClinicalTrials.gov Identifier: NCT00931255
Recruitment Status : Unknown
Verified December 2009 by University of Maryland.
Recruitment status was:  Recruiting
First Posted : July 2, 2009
Last Update Posted : December 15, 2009
Information provided by:

Study Description
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.

Condition or disease Intervention/treatment Phase
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

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.

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
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
Study Start Date : April 2009
Estimated Primary Completion Date : November 2011
Estimated Study Completion Date : February 2012

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. eGFR [ Time Frame: One year ]
  2. Change in eGFR from baseline to 1-year [ Time Frame: 1 year ]
  3. Graft survival (Actual, Actuarial) [ Time Frame: 1 year; up to 3 years ]
  4. Patient survival (Actual and Actuarial) [ Time Frame: 1-year; up to 3 years ]
  5. Incidence & severity of acute rejection (Actual, Actuarial) [ Time Frame: 1 year; up to 3 years ]
  6. Incidence of development of DSA [ Time Frame: Up to 3 years ]
  7. Incidence of BK nephropathy (Cumulative) [ Time Frame: Up to 3 years ]
  8. Change in inflammatory markers (including IL-6, MCP, CRP)from baseline [ Time Frame: 1 year ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Age => 18.
  2. Recipient of a deceased donor kidney transplant.
  3. Delayed graft function, defined as need for dialysis during first week after surgery or slow graft function, defined as creatinine >=3.0 by post-op day 5 without requiring dialysis
  4. Stable serum creatinine for 2 weeks prior to enrollment.
  5. Able to give informed consent.
  6. Compliant with medical regimen and clinic visits.

Exclusion Criteria:

  1. Episode of acute rejection within 4 weeks prior to enrollment.
  2. Calculated GFR < 30 ml/min.
  3. Interstitial fibrosis & tubular atrophy in transplant biopsy higher than grade II (Banff"05 update).
  4. Proteinuria > 500 mg/24 h or spot urine protein/creatinine > 0.5.
  5. Total fasting cholesterol level > 300 mg/dl or triglyceride > 500 mg/dl despite optimal lipid lowering therapy.
  6. Recipient of pancreas or liver allografts.
  7. Leukopenia (WBC < 3000 mm3) within 2 weeks prior to enrollment.
  8. Leukopenia (WBC < 2000 mm3) within 4 weeks prior to enrollment.
  9. Thrombocytopenia (platelets count < 100,000/mm3) within 2 weeks prior to enrollment.
  10. Unwilling to comply with study protocol.
  11. Enrollment in another drug trial that precludes use of sirolimus.
  12. Diagnosis of malignancy within 2 years prior to enrollment, except adequately treated non-melanoma skin cancer.
  13. For women, pregnancy.
  14. Allergy to iodine
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00931255

Contact: Abdolreza Haririan, MD, MPH 410-328-5720 ahariria@medicine.umaryland.edu
Contact: Caroline Pancotti, RN 410-328-5720 cpancott@medicine.umaryland.edu

United States, Maryland
University of Maryland Medical Center Recruiting
Baltimore, Maryland, United States, 21201
Contact: Caroline Pancotti, RN    410-328-5720    cpancott@medicine.umaryland.edu   
Contact: Hongxia Li    410-328-0206    hli@medicine.umaryland.edu   
Sub-Investigator: David Klassen, MD         
Sub-Investigator: Matthew Cooper, MD         
Sponsors and Collaborators
University of Maryland
Wyeth is now a wholly owned subsidiary of Pfizer
Principal Investigator: Abdolreza Haririan, MD, MPH University of Maryland
More Information

Responsible Party: Dr Abdolreza Haririan, MD, MPH, University of Maryland
ClinicalTrials.gov Identifier: NCT00931255     History of Changes
Other Study ID Numbers: HP-00042201
First Posted: July 2, 2009    Key Record Dates
Last Update Posted: December 15, 2009
Last Verified: December 2009

Keywords provided by University of Maryland:
kidney transplant
delayed graft function
Graft survival
Acute rejection
Chronic allograft nephropathy

Additional relevant MeSH terms:
Delayed Graft Function
Pathologic Processes
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents