Graft RejectionPhase 4NCT00369382
Study Of The Safety And Efficacy Of Conversion From A CNI To Sirolimus In Renally-Impaired Heart Transplant Recipients
A Phase 4 study testing cyclosporine or tacrolimus and sirolimus in people with Graft Rejection and Kidney Failure, run by Wyeth is now a wholly owned subsidiary of Pfizer at 23 sites in 7 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Graft Rejection, Kidney Failure
- What is being tested?
- cyclosporine or tacrolimus and sirolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 121 participants
- Where
- 23 sitesin 7 countries
- Study dates
- Sep 2006to May 2010
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
23 sites in 7 countries.
23 sites in 7 countries
United States8 sites
Pfizer Investigational Site
Houston, Texas, 77030
Pfizer Investigational Site
New York, New York, 10027-6902
Pfizer Investigational Site
Norfolk, Virginia, 23507
Pfizer Investigational Site
Philadelphia, Pennsylvania, 19102
Pfizer Investigational Site
Philadelphia, Pennsylvania, 19104
Pfizer Investigational Site
Pittsburgh, Pennsylvania, 15213
Pfizer Investigational Site
Rochester, Minnesota, 55905
Pfizer Investigational Site
Tampa, Florida, 33606
Spain7 sites
Pfizer Investigational Site
Barcelona, 08036
Pfizer Investigational Site
L'Hospitalet de Llobregat, Barcelona, 08907
Pfizer Investigational Site
La Coru?a, La Coru?a, 15001
Pfizer Investigational Site
Madrid, Madrid, 28035
Pfizer Investigational Site
Santander, Cantabria, 39008
Pfizer Investigational Site
Seville, Sevilla, 41013
Pfizer Investigational Site
Valencia, Valencia, 46009
Canada3 sites
Pfizer Investigational Site
Montreal, Quebec, H1T 1C8
Pfizer Investigational Site
Québec, Quebec, G1V 4G5
Pfizer Investigational Site
Sainte-Foy, Quebec, G1V 4G5
New Zealand2 sites
Pfizer Investigational Site
Auckland, New Zealand
Pfizer Investigational Site
Epsom, Auckland, 1003
Australia1 site
Pfizer Investigational Site
Darlinghurst, New South Wales, 2010
About this study
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
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
- Being tested
- cyclosporine or tacrolimus, sirolimus
- Keywords
- Heart Transplant, Kidney Failure
- Medical subject headings
- Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cyclosporine or tacrolimusDrug
Also called Brand names for cyclosporine are Neoral®, Sandimmune®, and Gengraf®; brand names for tacrolimus are Prograf® and Adagraf™.
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.
sirolimusDrug
Also called Rapamune®
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.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Group 1: Continuation of CNI regimen Receives: Drug: cyclosporine or tacrolimus |
| 2 | Experimental | Group 2: (CNI-Free) Conversion to SRL-based regimen Receives: Drug: sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline
Secondary outcomes (12)
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.
Measured: 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
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.
Measured: Baseline and Weeks 4, 16, 24, 32, 40 and 52
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.
Measured: Baseline
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.
Measured: Baseline and Weeks 4, 16, 24, 32, 40, and 52
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.
Measured: Baseline
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.
Measured: Baseline to discontinuation (up to Week 52)
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.
Measured: Baseline until death (up to Week 56)
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.
Measured: Baseline to Week 52
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.
Measured: Baseline to Week 52
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.
Measured: Baseline to Week 52
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.
Measured: Baseline to Week 52
Number of Participants in Sirolimus Treatment Group Requiring Conversion Back to CNI Therapy
Measured: Baseline up to Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2006 (estimated)
- Study startSep 2006
- Primary completionApr 2010
- Study completionMay 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Graft RejectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 121 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wyeth is now a wholly owned subsidiary of Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00369382
- Sponsor's protocol ID
- 0468E7-408
- Other IDs
- B1741006
- Status last verified
- May 2011
- First submitted
- 25 Aug 2006
- Last updated
- 30 May 2011
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 22776430
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00369382
- Acronym / sponsor ID
- 0468E7-408
- Conditions
- Graft Rejection, Kidney Failure
- Keywords
- Heart Transplant, Kidney Failure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 121 participants (actual)
- Lead sponsor
- Wyeth is now a wholly owned subsidiary of PfizerIndustry (pharma, biotech, devices)
- Study start
- Sep 2006
- Primary completion
- Apr 2010 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 29 Aug 2006 (estimated)
- Results
- Posted 23 May 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: cyclosporine or tacrolimusGroup 1: Continuation of CNI regimen |
| 2 | Experimental | Drug: sirolimusGroup 2: (CNI-Free) Conversion to SRL-based regimen |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cyclosporine or tacrolimusAlso: Brand names for cyclosporine are Neoral®, Sandimmune®, and Gengraf®; brand names for tacrolimus are Prograf® and Adagraf™.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. | Drug | 1 |
| sirolimusAlso: Rapamune®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. | Drug | 2 |
Primary outcome
Change From Baseline in Calculated Creatinine Clearance (Cockcroft-Gault Equation) at 52 Weeks Post-randomization
Time frame: Baseline and Week 52
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
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.
12 secondary outcomes
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
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
Calculated Creatinine Clearance (Modification of Diet in Renal Disease [MDRD] Equation) at Baseline
Time frame: Baseline
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
Serum Creatinine Level at Baseline
Time frame: Baseline
Annual Change in Calculated Creatinine Clearance (Cockcroft-Gault Equation)
Time frame: Baseline to discontinuation (up to Week 52)
Overall Survival (OS)
Time frame: Baseline until death (up to Week 56)
Number of Participants With Acute Rejection
Time frame: Baseline to Week 52
Number of Participants With Biopsy-confirmed Acute Rejection by Severity
Time frame: Baseline to Week 52
Time to First Acute Rejection
Time frame: Baseline to Week 52
Number of Participants Requiring Antibody Use in Treatment of Acute Rejection
Time frame: Baseline to Week 52
Number of Participants in Sirolimus Treatment Group Requiring Conversion Back to CNI Therapy
Time frame: Baseline up to Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2011.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22776430Zuckermann 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.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
Related trials for Graft Rejection
RecruitingObservational study
Long-term Evaluation and Follow-up Care of Patients Treated With Stem Cell Transplants
Graft-versus-leukemia, Graft vs Host Disease
RecruitingPhase 2
A Study to Learn About the Effects of Felzartamab Infusions in Adults With Kidney Transplants Who Have Late Isolated Microvascular Inflammation
Microvascular Inflammation
RecruitingPhase 1
A Study of LBP-MARCO and Ruxolitinib in People With Graft-Versus-Host Disease (GVHD)
Transplant Failure or Rejection of Bone Marrow (Graft vs Host Disease, GVHD)
Enrolling by invitationPhase 3
A Study to Learn More About the Long-Term Safety and Effects of Felzartamab Infusions in Adults With Kidney Transplants Who Have Antibody-Mediated Rejection (AMR) or Microvascular Inflammation (MVI) (TRANSCEND/TRANSPIRE LTE)
Antibody-mediated Rejection, Microvascular Inflammation
Not yet recruiting
Molecular Evidence of Rejection Intervention Trial
Heart Transplant Rejection
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
23 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing cyclosporine or tacrolimus and sirolimus in people with Graft Rejection and Kidney Failure, run by Wyeth is now a wholly owned subsidiary of Pfizer at 23 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 May 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in United States, Spain, Canada, New Zealand, Australia and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 May 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Calculated Creatinine Clearance (Cockcroft-Gault Equation) at 52 Weeks Post-randomization (time frame: Baseline and Week 52). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00369382, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2011.