- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00369382
Study Of The Safety And Efficacy Of Conversion From A CNI To Sirolimus In Renally-Impaired Heart Transplant Recipients
May 25, 2011 updated by: Wyeth is now a wholly owned subsidiary of Pfizer
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
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
121
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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New South Wales
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Darlinghurst, New South Wales, Australia, 2010
- Pfizer Investigational Site
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Vienna, Austria, A-1090
- Pfizer Investigational Site
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Quebec, Canada, G1V 4G5
- Pfizer Investigational Site
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Quebec
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Montreal, Quebec, Canada, H1T 1C8
- Pfizer Investigational Site
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Sainte-Foy, Quebec, Canada, G1V 4G5
- Pfizer Investigational Site
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Auckland, New Zealand
- Pfizer Investigational Site
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Auckland
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Epsom, Auckland, New Zealand, 1003
- Pfizer Investigational Site
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Barcelona, Spain, 08036
- Pfizer Investigational Site
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La Coru?a, Spain, 15001
- Pfizer Investigational Site
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Madrid, Spain, 28035
- Pfizer Investigational Site
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Sevilla, Spain, 41013
- Pfizer Investigational Site
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Valencia, Spain, 46009
- Pfizer Investigational Site
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Barcelona
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L'Hospitalet de Llobregat, Barcelona, Spain, 08907
- Pfizer Investigational Site
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Cantabria
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Santander, Cantabria, Spain, 39008
- Pfizer Investigational Site
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Bern, Switzerland, 3010
- Pfizer Investigational Site
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Florida
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Tampa, Florida, United States, 33606
- Pfizer Investigational Site
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Minnesota
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Rochester, Minnesota, United States, 55905
- Pfizer Investigational Site
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New York
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New York, New York, United States, 10027-6902
- Pfizer Investigational Site
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- Pfizer Investigational Site
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Philadelphia, Pennsylvania, United States, 19102
- Pfizer Investigational Site
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Pittsburgh, Pennsylvania, United States, 15213
- Pfizer Investigational Site
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Texas
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Houston, Texas, United States, 77030
- Pfizer Investigational Site
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Virginia
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Norfolk, Virginia, United States, 23507
- Pfizer Investigational Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
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:
- 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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Active Comparator: 1
Group 1: Continuation of CNI regimen
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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.
Other Names:
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Experimental: 2
Group 2: (CNI-Free) Conversion to SRL-based regimen
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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.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change From Baseline in Calculated Creatinine Clearance (Cockcroft-Gault Equation) at 52 Weeks Post-randomization
Time Frame: Baseline and Week 52
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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.
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Baseline and Week 52
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Calculated Creatinine Clearance (Cockcroft-Gault Equation) at Baseline
Time Frame: Baseline
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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.
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Baseline
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change From Baseline in Calculated Creatinine Clearance (Cockcroft-Gault Equation) at 4, 16, 24, 32, and 40 Weeks Post-randomization
Time Frame: Baseline and Weeks 4, 16, 24, 32, and 40
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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.
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Baseline and Weeks 4, 16, 24, 32, and 40
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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
Time Frame: Baseline and Weeks 4, 16, 24, 32, 40 and 52
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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.
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Baseline and Weeks 4, 16, 24, 32, 40 and 52
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Calculated Creatinine Clearance (Modification of Diet in Renal Disease [MDRD] Equation) at Baseline
Time Frame: Baseline
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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.
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Baseline
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Change From Baseline in Serum Creatinine Level at 4, 16, 24, 32, 40, and 52 Weeks Post-randomization
Time Frame: Baseline and Weeks 4, 16, 24, 32, 40, and 52
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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.
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Baseline and Weeks 4, 16, 24, 32, 40, and 52
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Serum Creatinine Level at Baseline
Time Frame: Baseline
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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.
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Baseline
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Annual Change in Calculated Creatinine Clearance (Cockcroft-Gault Equation)
Time Frame: Baseline to discontinuation (up to Week 52)
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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.
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Baseline to discontinuation (up to Week 52)
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Overall Survival (OS)
Time Frame: Baseline until death (up to Week 56)
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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.
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Baseline until death (up to Week 56)
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Number of Participants With Acute Rejection
Time Frame: Baseline to Week 52
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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.
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Baseline to Week 52
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Number of Participants With Biopsy-confirmed Acute Rejection by Severity
Time Frame: Baseline to Week 52
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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.
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Baseline to Week 52
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Time to First Acute Rejection
Time Frame: Baseline to Week 52
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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.
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Baseline to Week 52
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Number of Participants Requiring Antibody Use in Treatment of Acute Rejection
Time Frame: Baseline to Week 52
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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.
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Baseline to Week 52
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Number of Participants in Sirolimus Treatment Group Requiring Conversion Back to CNI Therapy
Time Frame: Baseline up to Week 52
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Baseline up to Week 52
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
September 1, 2006
Primary Completion (Actual)
April 1, 2010
Study Completion (Actual)
May 1, 2010
Study Registration Dates
First Submitted
August 25, 2006
First Submitted That Met QC Criteria
August 25, 2006
First Posted (Estimate)
August 29, 2006
Study Record Updates
Last Update Posted (Estimate)
May 30, 2011
Last Update Submitted That Met QC Criteria
May 25, 2011
Last Verified
May 1, 2011
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Kidney Diseases
- Urologic Diseases
- Renal Insufficiency
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Dermatologic Agents
- Anti-Bacterial Agents
- Antibiotics, Antineoplastic
- Antifungal Agents
- Calcineurin Inhibitors
- Tacrolimus
- Sirolimus
- Cyclosporine
- Cyclosporins
Other Study ID Numbers
- 0468E7-408
- B1741006 (Other Identifier: Pfizer)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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