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

Kidney Failure Clinical Trial

Official title:

A Randomized Open-Label Study To Compare The Safety And Efficacy Of Conversion From A Calcineurin Inhibitor To Sirolimus Vs Continued Use Of A Calcineurin Inhibitor In Heart Transplant Recipients With Mild-Moderate Impaired Renal Function

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00369382
• Other study ID #: 0468E7-408
• Secondary ID: B1741006
• Status: Completed
• Phase: Phase 4
• First received: August 25, 2006
• Last updated: May 25, 2011
• Start date: September 2006
• Est. completion date: May 2010

Study information

• Verified date: May 2011
• Source: Wyeth is now a wholly owned subsidiary of Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Human Research Ethics CommitteeAustria: Federal Ministry for Health and WomenCanada: Health CanadaNew Zealand: Health Research CouncilSpain: Ministry of HealthSwitzerland: SwissmedicUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 121
• Est. completion date: May 2010
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Cardiac transplant recipients age 18 years or older receiving cyclosporine or tacrolimus since the time of transplant.

• 12 months after cardiac transplantation but less than 96 months post-transplantation.

Exclusion Criteria:

• 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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Graft Rejection
• Kidney Failure
• Renal Insufficiency

Intervention

Drug:
• cyclosporine or tacrolimus
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.
• sirolimus
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.

Locations

Country	Name	City	State
Australia	Pfizer Investigational Site	Darlinghurst	New South Wales
Austria	Pfizer Investigational Site	Vienna
Canada	Pfizer Investigational Site	Montreal	Quebec
Canada	Pfizer Investigational Site	Quebec
Canada	Pfizer Investigational Site	Sainte-Foy	Quebec
New Zealand	Pfizer Investigational Site	Auckland
New Zealand	Pfizer Investigational Site	Epsom	Auckland
Spain	Pfizer Investigational Site	Barcelona
Spain	Pfizer Investigational Site	L'Hospitalet de Llobregat	Barcelona
Spain	Pfizer Investigational Site	La Coru?a
Spain	Pfizer Investigational Site	Madrid
Spain	Pfizer Investigational Site	Santander	Cantabria
Spain	Pfizer Investigational Site	Sevilla
Spain	Pfizer Investigational Site	Valencia
Switzerland	Pfizer Investigational Site	Bern
United States	Pfizer Investigational Site	Houston	Texas
United States	Pfizer Investigational Site	New York	New York
United States	Pfizer Investigational Site	Norfolk	Virginia
United States	Pfizer Investigational Site	Philadelphia	Pennsylvania
United States	Pfizer Investigational Site	Philadelphia	Pennsylvania
United States	Pfizer Investigational Site	Pittsburgh	Pennsylvania
United States	Pfizer Investigational Site	Rochester	Minnesota
United States	Pfizer Investigational Site	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Wyeth is now a wholly owned subsidiary of Pfizer

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  New Zealand,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	Change From Baseline in Calculated Creatinine Clearance (Cockcroft-Gault Equation) at 4, 16, 24, 32, and 40 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 = 90 mL/min/1.73m^2. Change from baseline=CC at Week X minus CC at baseline where higher scores represented improved renal function; Least squares mean adjusted for baseline calculated creatinine clearance and center.	Baseline and Weeks 4, 16, 24, 32, and 40	No
Secondary	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	Creatinine clearance calculated using MDRD equation. Normal adult creatinine clearance is = 90 mL/min/1.73m^2. Change from baseline=CC at Week X minus CC at baseline where higher scores represented improved renal function. Least squares mean adjusted for baseline calculated creatinine clearance (MDRD) and center.	Baseline and Weeks 4, 16, 24, 32, 40 and 52	No
Secondary	Calculated Creatinine Clearance (Modification of Diet in Renal Disease [MDRD] Equation) at Baseline	Creatinine clearance calculated using MDRD equation. 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	No
Secondary	Change From Baseline in Serum Creatinine Level at 4, 16, 24, 32, 40, and 52 Weeks Post-randomization	Serum creatinine is an indicator of kidney function. Creatinine is a substance formed from the metabolism of creatine, commonly found in blood, urine, and muscle tissue. It is removed from the blood by the kidneys and excreted in urine. Normal adult blood levels of creatinine=45 to 90 micromoles per liter (mcmol/L) for females, 60 to 110 mcmol/L for males, however normal values are age-dependent. Change from baseline=creatinine level at Week x minus baseline level where higher scores represented decreased kidney function. Least squares mean adjusted for treatment group and center.	Baseline and Weeks 4, 16, 24, 32, 40, and 52	No
Secondary	Serum Creatinine Level at Baseline	Serum creatinine is an indicator of kidney function. Creatinine is a substance formed from the metabolism of creatine, commonly found in blood, urine, and muscle tissue. It is removed from the blood by the kidneys and excreted in urine.	Baseline	No
Secondary	Annual Change in Calculated Creatinine Clearance (Cockcroft-Gault Equation)	The change in creatinine clearance over time assessed using the random coefficient slope of the regression line with creatinine clearance as the dependent variable and study day as the independent variable. Time points calculated as study days, relative to time of randomization of study medication. Observed data multiplied by a scale factor of 365 to express an annual change.	Baseline to discontinuation (up to Week 52)	No
Secondary	Overall Survival (OS)	Survival time from the start of study treatment to date of death due to any cause, censored at the last visit if no death. Death was determined from the Death report. The distribution of time to death was to be estimated using Kaplan-Meier method and compared between treatment groups with a proportional hazard model. The number and percent of survival at 6 and 12 months were to be reported.	Baseline until death (up to Week 56)	Yes
Secondary	Number of Participants With Acute Rejection	Based on International Society for Heart and Lung Transplantation [ISHLT] 1990 criteria: rejections Grade 3A or higher, rejection accompanied by hemodynamic compromise or requiring treatment. Grade 3A or higher included: multifocal aggressive infiltrates and/or myocyte damage, diffuse inflammatory process with necrosis, diffuse aggressive polymorphus with necrosis, increased infiltrates, and changes in edema, hemorrhage, or vasculitis. Biopsies performed for clinically suspected rejection (for cause), site's standard of care (site protocol biopsy), or protocol mandated.	Baseline to Week 52	Yes
Secondary	Number of Participants With Biopsy-confirmed Acute Rejection by Severity	Severity of acute rejection summarized using revised 2005 ISHLT criteria. Grade 0R: no rejection, Grade 1R: Focal (perivascular or interstitial) infiltrate without necrosis, diffuse but sparse infiltrate without necrosis, or one focus only with aggressive infiltration and/or focal myocyte damage, Grade 2R:Multifocal aggressive infiltrates and/or myocyte damage, and Grade 3R:Diffuse inflammatory process with necrosis, or diffuse aggressive polymorphous with necrosis, increased infiltrate, changes in edema, hemorrhage and vasculitis.	Baseline to Week 52	Yes
Secondary	Time to First Acute Rejection	Time from baseline to first biopsy-confirmed acute rejection defined as any of the following (based on ISHLT 1990 criteria): all rejections Grade 3A or higher, any rejection accompanied by hemodynamic compromise, or any rejection requiring treatment. ISHLT Grade 3A or higher included: Multifocal aggressive infiltrates and/or myocyte damage, diffuse inflammatory process with necrosis, diffuse aggressive polymorphus with necrosis, increased infiltrates, and changes in edema, hemorrhage, or vasculitis.	Baseline to Week 52	Yes
Secondary	Number of Participants Requiring Antibody Use in Treatment of Acute Rejection	Number of participants requiring antilymphocyte antibody therapy with suspected or biopsy-proven, steroid-resistant, acute rejection with or without hemodynamic compromise. Acute rejection based on ISHLT 1990 criteria: all rejections Grade 3A or higher, any rejection accompanied by hemodynamic compromise, or any rejection requiring treatment. ISHLT Grade 3A or higher included: Multifocal aggressive infiltrates and/or myocyte damage, diffuse inflammatory process with necrosis, diffuse aggressive polymorphus with necrosis, increased infiltrates, and changes in edema, hemorrhage, or vasculitis.	Baseline to Week 52	Yes
Secondary	Number of Participants in Sirolimus Treatment Group Requiring Conversion Back to CNI Therapy		Baseline up to Week 52	Yes

External Links

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