search
Back to results

Tacrolimus to Sirolimus Conversion for Delayed Graft Function (RAPA)

Primary Purpose

Kidney Transplant, Delayed Graft Function

Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Tacrolimus
Sirolimus
Sponsored by
University of Maryland, Baltimore
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Kidney Transplant focused on measuring kidney transplant, tacrolimus, sirolimus, delayed graft function, Graft survival, Acute rejection, Chronic allograft nephropathy

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Maryland Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Tacrolimus

Sirolimus

Arm Description

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.

5 mg, PO , daily

Outcomes

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

Secondary Outcome Measures

eGFR
Change in eGFR From Baseline to 1-year
Graft Survival (Actual, Actuarial)
Incidence of Acute Rejection (Actual, Actuarial)
Incidence of BK Nephropathy (Cumulative)
Change in Inflammatory Marker : CRP From Baseline
Change in Inflammatory Marker, IL-6 From Baseline
Change in Inflammatory Marker, MCP, From Baseline

Full Information

First Posted
June 29, 2009
Last Updated
March 29, 2022
Sponsor
University of Maryland, Baltimore
Collaborators
Wyeth is now a wholly owned subsidiary of Pfizer
search

1. Study Identification

Unique Protocol Identification Number
NCT00931255
Brief Title
Tacrolimus to Sirolimus Conversion for Delayed Graft Function
Acronym
RAPA
Official Title
Delayed Tacrolimus to Sirolimus Conversion in Renal Transplant Recipients With Delayed Graft Function
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Terminated
Why Stopped
The trial was stopped because of slow recruitment.
Study Start Date
April 2009 (undefined)
Primary Completion Date
June 2014 (Actual)
Study Completion Date
July 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Maryland, Baltimore
Collaborators
Wyeth is now a wholly owned subsidiary of Pfizer

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Transplant, Delayed Graft Function
Keywords
kidney transplant, tacrolimus, sirolimus, delayed graft function, Graft survival, Acute rejection, Chronic allograft nephropathy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
32 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tacrolimus
Arm Type
Active Comparator
Arm Description
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 Title
Sirolimus
Arm Type
Active Comparator
Arm Description
5 mg, PO , daily
Intervention Type
Drug
Intervention Name(s)
Tacrolimus
Other Intervention Name(s)
FK506, Prograf
Intervention Description
3-10 mg, PO, BID based on 12 hour trough on serum blood levels, adjusted according to protocol
Intervention Type
Drug
Intervention Name(s)
Sirolimus
Other Intervention Name(s)
Rapamune, Rapamycin
Intervention Description
5 mg, PO, daily based on 24 hour serum blood levels, adjusted according to protocol
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
eGFR
Time Frame
One year
Title
Change in eGFR From Baseline to 1-year
Time Frame
1 year
Title
Graft Survival (Actual, Actuarial)
Time Frame
1 year
Title
Incidence of Acute Rejection (Actual, Actuarial)
Time Frame
1 year
Title
Incidence of BK Nephropathy (Cumulative)
Time Frame
1 year
Title
Change in Inflammatory Marker : CRP From Baseline
Time Frame
1 year
Title
Change in Inflammatory Marker, IL-6 From Baseline
Time Frame
1 Year
Title
Change in Inflammatory Marker, MCP, From Baseline
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age => 18. Recipient of a deceased donor kidney transplant. 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 Stable serum creatinine for 2 weeks prior to enrollment. Able to give informed consent. Compliant with medical regimen and clinic visits. Exclusion Criteria: Episode of acute rejection within 4 weeks prior to enrollment. Calculated GFR < 30 ml/min. Interstitial fibrosis & tubular atrophy in transplant biopsy higher than grade II (Banff"05 update). Proteinuria > 500 mg/24 h or spot urine protein/creatinine > 0.5. Total fasting cholesterol level > 300 mg/dl or triglyceride > 500 mg/dl despite optimal lipid lowering therapy. Recipient of pancreas or liver allografts. Leukopenia (WBC < 3000 mm3) within 2 weeks prior to enrollment. Leukopenia (WBC < 2000 mm3) within 4 weeks prior to enrollment. Thrombocytopenia (platelets count < 100,000/mm3) within 2 weeks prior to enrollment. Unwilling to comply with study protocol. Enrollment in another drug trial that precludes use of sirolimus. Diagnosis of malignancy within 2 years prior to enrollment, except adequately treated non-melanoma skin cancer. For women, pregnancy. Allergy to iodine
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Abdolreza Haririan, MD, MPH
Organizational Affiliation
University of Maryland
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Maryland Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Tacrolimus to Sirolimus Conversion for Delayed Graft Function

We'll reach out to this number within 24 hrs