Renal Allograft Function and Histology Following Switching From A Tacrolimus to Sirolimus (SRL)-Based Immunosuppression-

NCT01166724 | Terminated Phase 3 Results DMC

• 1 other identifier: 09-702
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators hypothesize that Tacrolimus (Tac) withdrawal from a Tac, MMF and steroid based triple therapy regimen leads to long term improved/stabilized graft function (glomerular filtration rate, GFR) primarily as a consequence of halting CNI-induced fibrogenetic processes that mediate loss of functioning renal tissue. The investigators further hypothesize that the underlying fibrotic mechanism is mediated by pathophysiologic processes that promote epithelial to mesenchymal transition (EMT) (mediated by TGF- ƒÒ) and that early therapeutic intervention may reverse this process (mediated by BMP-7)4. To address these hypotheses the investigators propose the following clinical and mechanistic aims: The investigators will test the hypothesis that switching from Tac to SRL in a Tac based triple therapy regimen with MMF and steroids in living and or deceased donor renal transplant recipients leads to improvement in allograft structure and function at 2 years post-transplantation. The investigators will test this hypothesis in an open label controlled trial where stable renal allograft recipients on Tac, MMF, prednisone maintenance immunosuppression will undergo renal biopsy at 3-4 months post-transplantation and will be randomized to either a) Remain on Tac, MMF and prednisone (CNI-maintenance) or b) switch the Tac to SRL and continue MMF and prednisone. The investigators will then compare biopsy derived measures of allograft fibrosis (CADI, Sirius Red, Banff Chronicity Index) and GFR in the two groups

Conditions

Kidney Transplant

Keywords

Kidney transplant

Outcome Measures

Primary Outcomes (1)

• Biopsy-derived Measures of Fibrosis

  The primary analyses will compare biopsy-derived measures of fibrosis in the Tac-maintenance and SRL groups using the t-test.

  12 months

Secondary Outcomes (1)

• Change in iGFR

  12 months

Study Arms (2)

Sirolimus

ACTIVE COMPARATOR

patients will be switched from Tacrolimus to Sirolimus

Drug: Sirolimus; Drug: Tacrolimus

Tacrolimus

NO INTERVENTION

Patient will stay on Tacrolimus

Interventions

Sirolimus DRUG

Tacrolimus to Sirolimus

Sirolimus

Tacrolimus DRUG

dosage per trough level

Sirolimus

Eligibility Criteria

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

You may qualify if:

• Absence of clinical acute rejection in post-transplant period preceding randomization
• HLA-mismatched solitary first and second kidney transplant recipients
• Absence of any degree of rejection (Banff 2007) on renal biopsy at 3-6 months(+/- 2 months) post-transplant.
• Absence of post-transplant donor-specific antibody

You may not qualify if:

• HLA-identical transplants
• Contraindication or inability to undergo renal biopsy, like previous complications due to biopsies, anticoagulation, active infection, etc.
• Positive flow cross match, sensitized recipient, presence of donor-specific antibody.
• Rejection episode after transplantation, either cellular or humoral on for cause or renal biopsy.
• Rejection present on pre-randomization renal biopsy.
• Proteinuria greater than 0.3 gram/day
• Native kidney disease biopsy proven or likely glomerulonephritis, primary or recurrent FSGS, MPGN or primary or recurrent membranous GN.
• Hypertriglyceridemia \> 400 mg/dL (treated), LDL cholesterol \> 160 mg/dL while on optimal treatment.
• WBC \< 2000/mm3, ANC \< 1000 mm3, Platelet count \< 100,000 mm3
• Active wound issues.
• Primary non-function.
• Active BKV or CMV disease.
• Evidence of recurrent disease.
• Active infection
• Pregnancy

Sponsors & Collaborators

• The Cleveland Clinic: lead
• Pfizer: collaborator

Study Sites (1)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Interventions

Sirolimus; Tacrolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Limitations and Caveats

Early termination; Sponsor discontinued the study for corporate reasons. No data analyzed.

Results Point of Contact

• Title: Dr. Stuart Flechner
• Organization: Cleveland Clinic

FLECHNS@ccf.org

216 445-5772

Study Officials

• T Srinivas, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2010
• First Posted: July 21, 2010
• Study Start: July 1, 2010
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: June 7, 2017
• Results First Posted: June 7, 2017

Record last verified: 2017-02

Locations

US (1)