Tacrolimus to Sirolimus Conversion for Delayed Graft Function

NCT00931255 | Terminated Phase 4 Results DMC

• 1 other identifier: HP-00042201
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Kidney Transplant; Delayed Graft Function

Keywords

kidney transplant; tacrolimus; sirolimus; delayed graft function; Graft survival; Acute rejection; Chronic allograft nephropathy

Outcome Measures

Primary Outcomes (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

  One year

Secondary Outcomes (8)

• eGFR

  One year

• Change in eGFR From Baseline to 1-year

  1 year

• Graft Survival (Actual, Actuarial)

  1 year

• Incidence of Acute Rejection (Actual, Actuarial)

  1 year

• Incidence of BK Nephropathy (Cumulative)

  1 year

Study Arms (2)

Tacrolimus

ACTIVE COMPARATOR

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

Sirolimus

ACTIVE COMPARATOR

5 mg, PO , daily

Drug: Sirolimus

Interventions

Tacrolimus DRUG

3-10 mg, PO, BID based on 12 hour trough on serum blood levels, adjusted according to protocol

Also known as: FK506, Prograf

Tacrolimus

Sirolimus DRUG

5 mg, PO, daily based on 24 hour serum blood levels, adjusted according to protocol

Also known as: Rapamune, Rapamycin

Sirolimus

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• Wyeth is now a wholly owned subsidiary of Pfizer: collaborator

Study Sites (1)

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Conditions

Delayed Graft Function

Interventions

Tacrolimus; Sirolimus

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Limitations and Caveats

The trial was stopped because of slow enrollment. Hence, the target enrollment number was not achieved.

Results Point of Contact

• Title: Abdolreza Haririan, MD
• Organization: UMaryland

ahariria@medicine.umaryland.edu

410-328-5720

Study Officials

• Abdolreza Haririan, MD, MPH

  University of Maryland

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 29, 2009
• First Posted: July 2, 2009
• Study Start: April 1, 2009
• Primary Completion: June 1, 2014
• Study Completion: July 1, 2014
• Last Updated: March 31, 2022
• Results First Posted: March 16, 2018

Record last verified: 2022-03

Locations

US (1)