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Tacrolimus to Sirolimus Conversion for Delayed Graft Function (RAPA)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2009 by University of Maryland.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by:
University of Maryland
ClinicalTrials.gov Identifier:
NCT00931255
First received: June 29, 2009
Last updated: December 14, 2009
Last verified: December 2009
History of Changes
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Delayed Tacrolimus to Sirolimus Conversion in Renal Transplant Recipients With Delayed Graft Function

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Maryland:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • eGFR [ Time Frame: One year ] [ Designated as safety issue: Yes ]
  • Change in eGFR from baseline to 1-year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Graft survival (Actual, Actuarial) [ Time Frame: 1 year; up to 3 years ] [ Designated as safety issue: Yes ]
  • Patient survival (Actual and Actuarial) [ Time Frame: 1-year; up to 3 years ] [ Designated as safety issue: Yes ]
  • Incidence & severity of acute rejection (Actual, Actuarial) [ Time Frame: 1 year; up to 3 years ] [ Designated as safety issue: Yes ]
  • Incidence of development of DSA [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
  • Incidence of BK nephropathy (Cumulative) [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
  • Change in inflammatory markers (including IL-6, MCP, CRP)from baseline [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 80
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)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00931255

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

Locations
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
Investigators
Principal Investigator: Abdolreza Haririan, MD, MPH University of Maryland
  More Information

No publications provided

Responsible Party: Dr Abdolreza Haririan, MD, MPH, University of Maryland
ClinicalTrials.gov Identifier: NCT00931255     History of Changes
Other Study ID Numbers: HP-00042201, 04868X1-4515
Study First Received: June 29, 2009
Last Updated: December 14, 2009
Health Authority: United States: Institutional Review Board

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

Additional relevant MeSH terms:
Delayed Graft Function
Pathologic Processes
Sirolimus
Everolimus
Tacrolimus
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
 Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on June 18, 2013