Study Of The Safety And Efficacy Of Conversion From A CNI To Sirolimus In Renally-Impaired Heart Transplant Recipients
This study has been completed.
Sponsor:
Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by:
Wyeth is now a wholly owned subsidiary of Pfizer
ClinicalTrials.gov Identifier:
NCT00369382
First received: August 25, 2006
Last updated: May 25, 2011
Last verified: May 2011
- Full Text View
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Graft Rejection Kidney Failure |
Drug: cyclosporine or tacrolimus Drug: sirolimus |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention |
| 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 |
Resource links provided by NLM:
Further study details as provided by Wyeth is now a wholly owned subsidiary of Pfizer:
Primary Outcome Measures:
- Change From Baseline in Calculated Creatinine Clearance (Cockcroft-Gault Equation) at 52 Weeks Post-randomization [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]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.
- Calculated Creatinine Clearance (Cockcroft-Gault Equation) at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]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.
Secondary Outcome Measures:
- 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 ] [ Designated as safety issue: No ]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.
- 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 ] [ Designated as safety issue: No ]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.
- Calculated Creatinine Clearance (Modification of Diet in Renal Disease [MDRD] Equation) at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]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.
- 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 ] [ Designated as safety issue: No ]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.
- Serum Creatinine Level at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]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.
- Annual Change in Calculated Creatinine Clearance (Cockcroft-Gault Equation) [ Time Frame: Baseline to discontinuation (up to Week 52) ] [ Designated as safety issue: No ]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.
- Overall Survival (OS) [ Time Frame: Baseline until death (up to Week 56) ] [ Designated as safety issue: Yes ]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.
- Number of Participants With Acute Rejection [ Time Frame: Baseline to Week 52 ] [ Designated as safety issue: Yes ]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.
- Number of Participants With Biopsy-confirmed Acute Rejection by Severity [ Time Frame: Baseline to Week 52 ] [ Designated as safety issue: Yes ]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.
- Time to First Acute Rejection [ Time Frame: Baseline to Week 52 ] [ Designated as safety issue: Yes ]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.
- Number of Participants Requiring Antibody Use in Treatment of Acute Rejection [ Time Frame: Baseline to Week 52 ] [ Designated as safety issue: Yes ]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.
- Number of Participants in Sirolimus Treatment Group Requiring Conversion Back to CNI Therapy [ Time Frame: Baseline up to Week 52 ] [ Designated as safety issue: Yes ]
| Enrollment: | 121 |
| Study Start Date: | September 2006 |
| Study Completion Date: | May 2010 |
| Primary Completion Date: | April 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: 1
Group 1: Continuation of CNI regimen
|
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.
Other Name: Brand names for cyclosporine are Neoral®, Sandimmune®, and Gengraf®; brand names for tacrolimus are Prograf® and Adagraf™.
|
|
Experimental: 2
Group 2: (CNI-Free) Conversion to SRL-based regimen
|
Drug: 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.
Other Name: Rapamune®
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
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.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00369382
Locations
| United States, Florida | |
| Pfizer Investigational Site | |
| Tampa, Florida, United States, 33606 | |
| United States, Minnesota | |
| Pfizer Investigational Site | |
| Rochester, Minnesota, United States, 55905 | |
| United States, New York | |
| Pfizer Investigational Site | |
| New York, New York, United States, 10027-6902 | |
| United States, Pennsylvania | |
| Pfizer Investigational Site | |
| Philadelphia, Pennsylvania, United States, 19102 | |
| Pfizer Investigational Site | |
| Philadelphia, Pennsylvania, United States, 19104 | |
| Pfizer Investigational Site | |
| Pittsburgh, Pennsylvania, United States, 15213 | |
| United States, Texas | |
| Pfizer Investigational Site | |
| Houston, Texas, United States, 77030 | |
| United States, Virginia | |
| Pfizer Investigational Site | |
| Norfolk, Virginia, United States, 23507 | |
| Australia, New South Wales | |
| Pfizer Investigational Site | |
| Darlinghurst, New South Wales, Australia, 2010 | |
| Austria | |
| Pfizer Investigational Site | |
| Vienna, Austria, A-1090 | |
| Canada, Quebec | |
| Pfizer Investigational Site | |
| Montreal, Quebec, Canada, H1T 1C8 | |
| Pfizer Investigational Site | |
| Sainte-Foy, Quebec, Canada, G1V 4G5 | |
| Canada | |
| Pfizer Investigational Site | |
| Quebec, Canada, G1V 4G5 | |
| New Zealand | |
| Pfizer Investigational Site | |
| Epsom, Auckland, New Zealand, 1003 | |
| Pfizer Investigational Site | |
| Auckland, New Zealand | |
| Spain | |
| Pfizer Investigational Site | |
| L'Hospitalet de Llobregat, Barcelona, Spain, 08907 | |
| Pfizer Investigational Site | |
| Santander, Cantabria, Spain, 39008 | |
| Pfizer Investigational Site | |
| Barcelona, Spain, 08036 | |
| Pfizer Investigational Site | |
| La Coru?a, Spain, 15001 | |
| Pfizer Investigational Site | |
| Madrid, Spain, 28035 | |
| Pfizer Investigational Site | |
| Sevilla, Spain, 41013 | |
| Pfizer Investigational Site | |
| Valencia, Spain, 46009 | |
| Switzerland | |
| Pfizer Investigational Site | |
| Bern, Switzerland, 3010 | |
Sponsors and Collaborators
Wyeth is now a wholly owned subsidiary of Pfizer
Investigators
| Study Director: | Pfizer CT.gov Call Center | Pfizer |
More Information
Additional Information:
No publications provided by Wyeth is now a wholly owned subsidiary of Pfizer
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Director, Clinical Trial Disclosure Group, Pfizer, Inc |
| ClinicalTrials.gov Identifier: | NCT00369382 History of Changes |
| Other Study ID Numbers: | 0468E7-408, B1741006 |
| Study First Received: | August 25, 2006 |
| Results First Received: | April 26, 2011 |
| Last Updated: | May 25, 2011 |
| Health Authority: | Australia: Human Research Ethics Committee Austria: Federal Ministry for Health and Women Canada: Health Canada New Zealand: Health Research Council Spain: Ministry of Health Switzerland: Swissmedic United States: Food and Drug Administration |
Keywords provided by Wyeth is now a wholly owned subsidiary of Pfizer:
|
Heart Transplant Kidney Failure |
Additional relevant MeSH terms:
|
Renal Insufficiency Kidney Diseases Urologic Diseases Cyclosporins Cyclosporine Sirolimus Everolimus Tacrolimus Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions |
Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antifungal Agents Anti-Infective Agents Therapeutic Uses Dermatologic Agents Antirheumatic Agents Antibiotics, Antineoplastic Antineoplastic Agents Anti-Bacterial Agents |
ClinicalTrials.gov processed this record on June 18, 2013