Study Of The Safety And Efficacy Of Conversion From A CNI To Sirolimus In Renally-Impaired Heart Transplant Recipients

NCT00369382 | Completed Phase 4 Results DMC

• 2 other identifiers: 0468E7-408B1741006
• Study Type: interventional
• Target: 121
• Locations: 6 countries
• Sites: 22

Brief Summary

The primary purpose of this study is to determine whether converting from calcineurin inhibitor (CNI) therapy to sirolimus therapy will be more effective than continuing calcineurin inhibitor therapy with respect to renal function in cardiac transplant recipients with mild to moderate renal dysfunction.

Conditions

Graft Rejection; Kidney Failure

Keywords

Heart Transplant; Kidney Failure

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Calculated Creatinine Clearance (Cockcroft-Gault Equation) at 52 Weeks Post-randomization

  Creatinine Clearance (CC) calculated using Cockcroft-Gault equation, adjusted for body surface area. Calculated CC: method to approximate kidney function. It measures rate creatinine (substance formed from metabolism of creatine) is cleared from blood by kidneys. Normal adult creatinine clearance is greater than or equal to (≥) 90 milliliters per minute per 1.73 meters squared (mL/min/1.73m\^2). Change from baseline=CC at Week 52 minus CC at baseline where higher scores represented improved renal function; Least squares mean adjusted for baseline calculated creatinine clearance and center.

  Baseline and Week 52

• Calculated Creatinine Clearance (Cockcroft-Gault Equation) at Baseline

  Creatinine clearance at baseline calculated using Cockcroft-Gault equation and adjusted for body surface area. Calculated CC: method to approximate kidney function. It measures rate creatinine (substance formed from metabolism of creatine) is cleared from blood by kidneys. Normal adult creatinine clearance is ≥ 90 mL/min/1.73m\^2.

  Baseline

Secondary Outcomes (12)

• Change From Baseline in Calculated Creatinine Clearance (Cockcroft-Gault Equation) at 4, 16, 24, 32, and 40 Weeks Post-randomization

  Baseline and Weeks 4, 16, 24, 32, and 40

• Change From Baseline in Calculated Creatinine Clearance (Modification of Diet in Renal Disease [MDRD] Equation) at 4, 16, 24, 32, 40 and 52 Weeks Post-randomization

  Baseline and Weeks 4, 16, 24, 32, 40 and 52

• Calculated Creatinine Clearance (Modification of Diet in Renal Disease [MDRD] Equation) at Baseline

  Baseline

• Change From Baseline in Serum Creatinine Level at 4, 16, 24, 32, 40, and 52 Weeks Post-randomization

  Baseline and Weeks 4, 16, 24, 32, 40, and 52

• Serum Creatinine Level at Baseline

  Baseline

Study Arms (2)

1

ACTIVE COMPARATOR

Group 1: Continuation of CNI regimen

Drug: cyclosporine or tacrolimus

2

EXPERIMENTAL

Group 2: (CNI-Free) Conversion to SRL-based regimen

Drug: sirolimus

Interventions

cyclosporine or tacrolimus DRUG

Cyclosporine and tacrolimus are provided by the sites and dosed to achieve a target trough level determined by the investigator; therefore, form, dosage, and frequency are site and patient specific. Duration should be 52 weeks on-therapy.

Also known as: Brand names for cyclosporine are Neoral®, Sandimmune®, and Gengraf®; brand names for tacrolimus are Prograf® and Adagraf™.

1

sirolimus DRUG

Oral (1 and 2 mg) tablets, dosing should be once daily to achieve a target trough level of 7- 15 ng/mL. Duration should be 52 weeks on-therapy.

Also known as: Rapamune®

2

Eligibility Criteria

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

You may qualify if:

• Cardiac transplant recipients age 18 years or older receiving cyclosporine or tacrolimus since the time of transplant.
• months after cardiac transplantation but less than 96 months post-transplantation.

You may not qualify if:

• Multiple-organ transplant recipients (such as heart-lung, heart-kidney, or heart after kidney transplant recipients).
• Prior or current use of sirolimus or everolimus unless administration was part of a "CNI holiday" lasting no more than 10 days.
• History of acute rejection within the last 3 months, malignancy within the last 5 years (except for adequately treated basal cell or squamous cell carcinoma of the skin), and human immunodeficiency virus (HIV) patients.

Sponsors & Collaborators

• Wyeth is now a wholly owned subsidiary of Pfizer: lead

Study Sites (23)

Pfizer Investigational Site

Tampa, Florida, 33606, United States

Location

Pfizer Investigational Site

Rochester, Minnesota, 55905, United States

Location

Pfizer Investigational Site

New York, New York, 10027-6902, United States

Location

Pfizer Investigational Site

Philadelphia, Pennsylvania, 19102, United States

Location

Pfizer Investigational Site

Philadelphia, Pennsylvania, 19104, United States

Location

Pfizer Investigational Site

Pittsburgh, Pennsylvania, 15213, United States

Location

Pfizer Investigational Site

Houston, Texas, 77030, United States

Location

Pfizer Investigational Site

Norfolk, Virginia, 23507, United States

Location

Pfizer Investigational Site

Darlinghurst, New South Wales, 2010, Australia

Location

Pfizer Investigational Site

Vienna, A-1090, Austria

Location

Pfizer Investigational Site

Montreal, Quebec, H1T 1C8, Canada

Location

Pfizer Investigational Site

Québec, Quebec, G1V 4G5, Canada

Location

Pfizer Investigational Site

Sainte-Foy, Quebec, G1V 4G5, Canada

Location

Pfizer Investigational Site

Epsom, Auckland, 1003, New Zealand

Location

Pfizer Investigational Site

Auckland, New Zealand, New Zealand

Location

Pfizer Investigational Site

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Pfizer Investigational Site

Santander, Cantabria, 39008, Spain

Location

Pfizer Investigational Site

La Coru?a, La Coru?a, 15001, Spain

Location

Pfizer Investigational Site

Madrid, Madrid, 28035, Spain

Location

Pfizer Investigational Site

Seville, Sevilla, 41013, Spain

Location

Pfizer Investigational Site

Valencia, Valencia, 46009, Spain

Location

Pfizer Investigational Site

Barcelona, 08036, Spain

Location

Pfizer Investigational Site

Bern, 3010, Switzerland

Location

Related Publications (1)

• Zuckermann A, Keogh A, Crespo-Leiro MG, Mancini D, Vilchez FG, Almenar L, Brozena S, Eisen H, Tai SS, Kushwaha S. Randomized controlled trial of sirolimus conversion in cardiac transplant recipients with renal insufficiency. Am J Transplant. 2012 Sep;12(9):2487-97. doi: 10.1111/j.1600-6143.2012.04131.x. Epub 2012 Jul 9.

  PMID: 22776430 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Renal Insufficiency

Interventions

Cyclosporine; Tacrolimus; Cyclosporins; Sirolimus

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: August 25, 2006
• First Posted: August 29, 2006
• Study Start: September 1, 2006
• Primary Completion: April 1, 2010
• Study Completion: May 1, 2010
• Last Updated: May 30, 2011
• Results First Posted: May 23, 2011

Record last verified: 2011-05

Locations

CH (1); US (8); NZ (2); AU (1); ES (7); CA (3)