Planned Conversion From TAC to SRL-based Regimen in de Novo Kidney Transplant Recipients

Outcomes of Planned Conversion From Tacrolimus to Sirolimus-based Immunosuppressive Regimen in de Novo Kidney Transplant Recipients

Background Early conversion from calcineurin inhibitor to mammalian target of rapamycin inhibitor is one of the immunosuppressive strategies that have been investigated to mitigate long-term CNi associated adverse events. This study aims to evaluate the conversion from tacrolimus to sirolimus in de novo kidney transplant recipients.

This multicenter, open-label study, planned to enroll 297 patients initially treated with tacrolimus, enteric-coated mycophenolate sodium (1440 mg/day, orally) and prednisone. The primary objective is to show superior glomerular filtration rate in the SRL group at 24 months after transplantation.

Study Overview

• Status: Completed
• Conditions: Kidney Transplant
• Intervention / Treatment: Drug: Conversion from Tacrolimus to Sirolimus; Drug: Maintenance on tacrolimus

• Study Type: Interventional
• Enrollment (Actual): 320
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil
    • Nephrology Service, Bonsucesso General Hospital. Rio de Janeiro, Brazil
  • São Paulo, Brazil, 04038
    • Nephrology Division, Hospital do Rim, Federal University of São Paulo, Brazil
  • São Paulo, Brazil, 04038
    • Renal Transplant Service, Hospital das Clínicas, University of São Paulo School of Medicine, São Paulo, Brazil.
  • Paraná
    • Curitiba, Paraná, Brazil
      • Hospital University Evangélico de Curitiba, Curitiba, Parana, Brazil
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil
      • Kidney & Pancreas Transplant Unit, Santa Casa de Misericordia, Porto Alegre, Brazil
  • São Paulo
    • São Jose do Rio Preto, São Paulo, Brazil, 04038
      • Instituto de Urologia e Nefrologia & Medical School-FAMERP/HB-FUNFARME, São José do Rio Preto-SP, Brazil

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients older than 18 years,
• recipients of first kidney transplant from brain dead deceased or living related non-HLA identical donors not older than 65 years,
• patients had to receive an ABO compatible organ with a CDC negative crossmatch and a peak panel reactive antibody lower that 30%,
• all patients agreed to use contraceptive methods during the study and up to 3 months after study drug discontinuation.

Exclusion Criteria:

• patients with chronic kidney diseases due to focal and segmental glomerulosclerosis and membranoproliferative glomerulonephritis,
• patients with active infection or positive for hepatitis B or C or human immunodeficiency viruses,
• patients with previous history of malignancy,
• patients with significant hematological or metabolic laboratorial abnormalities.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sirolimus; Conversion from Tacrolimus to Sirolimus	Drug: Conversion from Tacrolimus to Sirolimus
Active Comparator: Tacrolimus; Maintenance on tacrolimus	Drug: Maintenance on tacrolimus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Renal Function calculated using the 4 variable MDRD formula	24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Survival free from first treated biopsy confirmed acute rejection episodes (tBCAR) > IA according to Banff 1997 classification.	24 months
Incidence of all treated acute rejections.	24 months
Incidence and severity of all tBCAR.	24 months
Patient and graft survival.	24 months
Incidence of treatment discontinuation	24 months
Incidence of adverse events.	24 months

Collaborators and Investigators

• Sponsor: Helio Tedesco Silva Junior
• Collaborators: Pfizer
• Investigators: Principal Investigator: Helio T. Silva Junior, PhD, Nephrology Division, Hospital do Rim, Federal University of São Paulo, Brazil; Study Chair: Claudia R. Felipe, PhD, Nephrology Division, Hospital do Rim, Federal University of São Paulo, Brazil; Study Chair: Valter D. Garcia, PhD, Kidney & Pancreas Transplant Unit, Santa Casa de Misericordia, Porto Alegre, Brazil; Study Chair: Elias D. Neto, PhD, Renal Transplant Service, Hospital das Clínicas, University of São Paulo School of Medicine, São Paulo, Brazil; Study Chair: Mario A. Filho, PhD, Instituto de Urologia e Nefrologia & Medical School-FAMERP/HB-FUNFARME, São José do Rio Preto-SP, Brazil; Study Chair: Fabiana LC Cortieri, PhD, Hospital University Evangélico de Curitiba, Curitiba, Parana, Brazil; Study Chair: Deise BM Carvalho, PhD, Nephrology Service, Bonsucesso General Hospital. Rio de Janeiro, Brazil; Study Director: Jose OM Pestana, PhD, Nephrology Division, Hospital do Rim, Federal University of São Paulo, Brazil

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: February 22, 2013
• First Submitted That Met QC Criteria: February 27, 2013
• First Posted (Estimate): March 1, 2013

Study Record Updates

• Last Update Posted (Estimate): March 1, 2013
• Last Update Submitted That Met QC Criteria: February 27, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: tacrolimus; sirolimus; early conversion
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Calcineurin Inhibitors; Tacrolimus; Sirolimus
• Other Study ID Numbers: 0468E8-3328