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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00369382




Registration number
NCT00369382
Ethics application status
Date submitted
25/08/2006
Date registered
29/08/2006
Date last updated
30/05/2011

Titles & IDs
Public title
Study Of The Safety And Efficacy Of Conversion From A CNI To Sirolimus In Renally-Impaired Heart Transplant Recipients
Scientific 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
Secondary ID [1] 0 0
B1741006
Secondary ID [2] 0 0
0468E7-408
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Graft Rejection 0 0
Kidney Failure 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - cyclosporine or tacrolimus
Treatment: Drugs - sirolimus

Active Comparator: 1 - Group 1: Continuation of CNI regimen

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


Treatment: Drugs: 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.

Treatment: Drugs: 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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline and Week 52
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
Baseline
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline and Weeks 4, 16, 24, 32, and 40
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Baseline and Weeks 4, 16, 24, 32, 40 and 52
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Baseline
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Baseline and Weeks 4, 16, 24, 32, 40, and 52
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
Baseline
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
Baseline to discontinuation (up to Week 52)
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
Baseline until death (up to Week 56)
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
Baseline to Week 52
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
Baseline to Week 52
Secondary outcome [10] 0 0
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.
Timepoint [10] 0 0
Baseline to Week 52
Secondary outcome [11] 0 0
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.
Timepoint [11] 0 0
Baseline to Week 52
Secondary outcome [12] 0 0
Number of Participants in Sirolimus Treatment Group Requiring Conversion Back to CNI Therapy
Timepoint [12] 0 0
Baseline up to Week 52

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Pfizer Investigational Site - Darlinghurst
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Minnesota
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Pennsylvania
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
United States of America
State/province [6] 0 0
Virginia
Country [7] 0 0
Austria
State/province [7] 0 0
Vienna
Country [8] 0 0
Canada
State/province [8] 0 0
Quebec
Country [9] 0 0
New Zealand
State/province [9] 0 0
Auckland
Country [10] 0 0
Spain
State/province [10] 0 0
Barcelona
Country [11] 0 0
Spain
State/province [11] 0 0
Cantabria
Country [12] 0 0
Spain
State/province [12] 0 0
La Coru?a
Country [13] 0 0
Spain
State/province [13] 0 0
Madrid
Country [14] 0 0
Spain
State/province [14] 0 0
Sevilla
Country [15] 0 0
Spain
State/province [15] 0 0
Valencia
Country [16] 0 0
Switzerland
State/province [16] 0 0
Bern

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Wyeth is now a wholly owned subsidiary of Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00369382
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications