Efficacy and Safety of Everolimus in Recipients of Heart Transplants to Prevent Acute and Chronic Rejection
A 24-month, Multi-center, Randomized, Open-label, Non-inferiority Study of Efficacy and Safety Comparing Two Exposures of Concentration-controlled Everolimus With Reduced Cyclosporine Versus 3.0 g Mycophenolate Mofetil With Standard Dose Cyclosporine in de Novo Heart Transplant Recipients
Přehled studie
Postavení
Podmínky
Intervence / Léčba
Typ studie
Zápis (Aktuální)
Fáze
- Fáze 3
Kontakty a umístění
Studijní místa
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Buenos Aires, Argentina
- Fundacion Favalaro
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Santa Fe
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Rosario, Santa Fe, Argentina
- Sanatorio Parque
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New South Wales
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Darlinghurst, New South Wales, Austrálie
- St Vincents Hospital
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Queensland
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Chermside, Queensland, Austrálie
- Prince Charles Hospital
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Western Australia
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Perth, Western Australia, Austrálie
- Royal Perth Hospital
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Bruxelles, Belgie
- Cliniques universitaires Saint-Luc
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Lyon, Francie
- Hopital Cardiologique de Lyon
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Paris, Francie
- Hôpital Pitie Salpétrière
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Paris, Francie
- Hopital Georges Pompidou
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Strasbourg, Francie
- CHU de Strasbourg Hopital Civil Medicale B
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Vandoeuvre les Nancy, Francie
- CHU Hopital de Brabois
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Bologna, Itálie
- Az. Osp. di Bologna Policl. S. Orsola-Malpighi Univ. degli Studi
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Cagliari, Itálie
- Azienda Ospedaliera G. Brotzu
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Padova, Itálie
- A.O.-Universita di Padova-Universita degli Studi
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Pavio, Itálie
- Fodazione IRCCS Policlinico S. Matteo
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Roma, Itálie
- Azienda Ospedaliera S. Camillo-Forlanini
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Torino, Itálie
- Az. Ospedaliero-Universitaria S. Giovanni Battista di Torino
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Alberta
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Edmonton, Alberta, Kanada
- University of Alberta Hospital
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British Columbia
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Vancouver, British Columbia, Kanada
- St Paul's Hospital
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Nova Scotia
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Halifax, Nova Scotia, Kanada
- New Halifax Infirmary
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Ontario
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Toronto, Ontario, Kanada
- Toronto General Hospital
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Quebec
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Sainte-Foy, Quebec, Kanada
- Institut Univ. de cardiologie et pneumologie de Quebec
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Oslo, Norsko
- Rikshospitalet, Hjertemedisinskavdeling
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Auckland, Nový Zéland
- Auckland Hospital
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Bad Oeynhausen, Německo
- Herz- u. Diabeteszentrum NRW/Ruhr-Univ. Bochum
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Berlin, Německo
- Deutsches Herzzentrum Berlin
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Hamburg, Německo
- Universitaetsklinikum Hamburg-Eppendorf
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Hannover, Německo
- Kliniken der Med. Hochschule
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Kiel, Německo
- Universitaetsklinikum Kiel
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Regensburg, Německo
- Universitaetsklinik Regensburg
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San Juan, Portoriko
- Cardiovascular Center of Puerto Rico and the Caribbean
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Vienna, Rakousko
- Universitaet Wien
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Birmingham, Spojené království
- Queen Elizabeth Hospital
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Cambridge, Spojené království
- Papworth Hospital
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Manchester, Spojené království
- Wythenshawe Hospital
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California
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Los Angeles, California, Spojené státy
- UCLA Medical Center
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San Francisco, California, Spojené státy
- California Pacific Medical Center
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Stanford, California, Spojené státy
- Stanford U Sch, Falk Cardiovasular Research Ctr.
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Florida
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Gainesville, Florida, Spojené státy
- University of Florida Shands Hospital
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Georgia
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Atlanta, Georgia, Spojené státy
- Emory University Hospital
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Illinois
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Maywood, Illinois, Spojené státy
- Loyola Univerisity Medical School
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Massachusetts
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Boston, Massachusetts, Spojené státy
- Massachusetts General Hospital
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Boston, Massachusetts, Spojené státy
- Tufts Medical Center
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Michigan
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Ann Arbor, Michigan, Spojené státy
- University of Michigan Health System
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Missouri
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St. Louis, Missouri, Spojené státy
- Washington University School of Medicine
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New York
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New York, New York, Spojené státy
- Columbia University Medical Center
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New York, New York, Spojené státy
- Recanati Miller Transplant Institute
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North Carolina
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Chapel Hill, North Carolina, Spojené státy
- UNC Division of Cardiology
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Durham, North Carolina, Spojené státy
- Duke University Heart Failure Research
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Ohio
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Cleveland, Ohio, Spojené státy
- Cleveland Clinic Foundation
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Pennsylvania
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Hershey, Pennsylvania, Spojené státy
- Penn State College of Medicine
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Philadelphia, Pennsylvania, Spojené státy
- Temple University Hospital
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Philadelphia, Pennsylvania, Spojené státy
- Thomas Jefferson University Hospital
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Philadelphia, Pennsylvania, Spojené státy
- Hahnemann University Hospital
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South Carolina
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Charleston, South Carolina, Spojené státy
- Medical University of South Carolina
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Texas
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Austin, Texas, Spojené státy
- Texas Cardiovascular Consultants
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Galveston, Texas, Spojené státy
- University of Texas Medical Branch, Div of Cardio Thoracic
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Houston, Texas, Spojené státy, 77030
- Methodist Hospital/DeBakey Heart Failure Research Center
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Utah
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Murray, Utah, Spojené státy
- Intermountain Medical Center
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Wisconsin
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Madison, Wisconsin, Spojené státy, 53792
- University of Wisconsin - Madison Medical School
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Milwakee, Wisconsin, Spojené státy
- St. Luke's Medical Center Cardiac Services
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Taipei, Tchaj-wan
- National Taiwan University Hospital
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Cordoba, Španělsko
- Hospital Universitario Reina Sofia
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Madrid, Španělsko
- Hospital Puerta de Hierro Majadahonda
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
- Male or female cardiac recipients 18-70 years of age undergoing primary heart transplantation.
- The graft must be functional at time of randomization.
Exclusion Criteria:
- Patients who are recipients of multiple solid organ transplants or tissue transplants or have previously received organ transplants.
- Patients who are recipients of ABO incompatible transplants.
Other protocol-defined inclusion/exclusion criteria may apply.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Experimentální: everolimus 1.5 mg
Within 72 hours after transplantation participants received 0.75 mg everolimus tablets twice a day 12 hours apart for a total 1.5 mg daily dose in combination with reduced cyclosporine and standard dose corticosteroids for 24 months.
The everolimus dose could be adjusted to maintain a target everolimus trough level of 3-8 ng/mL.
|
Everolimus supplied as 0.75 mg tablets.
Everolimus was also supplied in 0.25 mg and 0.5 mg tablets for dose adjustments.
Ostatní jména:
Cyclosporine reduced dose in the everolimus arms (approximately half of the standard dose) and standard dose in the mycophenolate mofetil arm.
Ostatní jména:
Corticosteroids standard dose.
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Experimentální: everolimus 3.0 mg
Within 72 hours after transplantation participants received 1.5 mg everolimus tablets twice a day 12 hours apart for a total 3.0 mg daily dose in combination with reduced cyclosporine and standard dose corticosteroids for 24 months. The everolimus dose could be adjusted to maintain a target everolimus trough level of 6-12 ng/mL. Randomization of new patients in this arm was prematurely stopped as of 27 March 2008 due to high mortality rate, as per Data Monitoring Committee. |
Everolimus supplied as 0.75 mg tablets.
Everolimus was also supplied in 0.25 mg and 0.5 mg tablets for dose adjustments.
Ostatní jména:
Cyclosporine reduced dose in the everolimus arms (approximately half of the standard dose) and standard dose in the mycophenolate mofetil arm.
Ostatní jména:
Corticosteroids standard dose.
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Aktivní komparátor: mycophenolate mofetil
Within 72 hours after transplantation participants received 3 tablets 500 mg mycophenolate mofetil twice a day 12 hours apart for a total daily dose of 3000 mg in combination with a standard cyclosporine dose and standard dose corticosteroids for 24 months.
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Cyclosporine reduced dose in the everolimus arms (approximately half of the standard dose) and standard dose in the mycophenolate mofetil arm.
Ostatní jména:
Corticosteroids standard dose.
Mycophenolate mofetil supplied as 500 mg tablets.
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Percentage of Participants With Composite Efficacy Failure at 12 Months
Časové okno: 12 Months
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Composite efficacy failure was defined as Biopsy Proven Acute Rejection(BPAR) of International Society for Heart and Lung Transplantation(ISHLT) grade ≥3A, Acute Rejection associated with Hemodynamic Compromise, Graft loss/Retransplant, Death or Loss to follow-up. Identification of acute rejection was based on the local pathologist's evaluation of endomyocardial biopsy slides. Hemodynamic compromise was present if 1 or more of the following were met: Ejection fraction ≤30% or 25% lower than Baseline or Fractional shortening ≤20% or 25% lower than Baseline and/or use of inotropic treatment. |
12 Months
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Percentage of Participants With Graft Loss/Re-transplant, Death or Loss to Follow-up at 12 Months
Časové okno: 12 Months
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Loss to follow-up for this composite endpoint included participants who did not experience graft loss/re-transplant or death and whose last day of contact was prior to Day 316 (start day of the Month 12 visit window).
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12 Months
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Renal Function Measured by Glomerular Filtration Rate (GFR) at 12 Months
Časové okno: 12 Months
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GFR was calculated using the Modification of Diet and Renal Disease (MDRD) formula: GFR [mL/min/1.73m^2] = 186.3*(C^-1.154)*(A^-0.203)*G*R where C is the serum concentration of creatinine [mg/dL] A is age [years] G=0.742 when gender is female, otherwise G=1 R=1.21 when race is black, otherwise R=1 |
12 Months
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Change From Baseline in the Average Maximum Intimal Thickness at Month 12
Časové okno: Baseline, Month 12
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Maximum intimal thickness was assessed using Intravascular Ultrasound (IVUS).
IVUS is a technique for taking ultrasound pictures of the wall of an artery from inside the artery itself.
It shows the thickness of the artery wall and any narrowing of the artery.
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Baseline, Month 12
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Percentage of Participants With Cardiac Allograft Vasculopathy (CAV) at Month 12
Časové okno: 12 Months
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Cardiac allograft vasculopathy is defined as a 0.5 mm increase in maximum intimal thickness as measured by Intravascular Ultrasound (IVUS) in at least one matched slice between baseline and Month 12.
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12 Months
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Percentage of Participants With Biopsy-proven Acute Rejection (BPAR of ISHLT Grade ≥ 3A), Acute Rejection Associated With Hemodynamic Compromise (HDC), Graft Loss/Re-transplant and Death at Month 12
Časové okno: 12 Months
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Identification of acute rejections was based on the local pathologist's evaluation of endomyocardial biopsy slides. Hemodynamic compromise was present if 1 or more of the following were met: Ejection fraction ≤ 30% or 25% lower than Baseline or Fractional shortening ≤ 20% or 25% lower than Baseline, and/or use of inotropic treatment. |
12 Months
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Percentage of Participants With Composite Efficacy Failure at 24 Months
Časové okno: 24 Months
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Composite efficacy failure was defined as Biopsy Proven Acute Rejection (BPAR) of International Society for Heart and Lung Transplantation grade ≥ 3A, Acute Rejection associated with Hemodynamic Compromise, Graft loss/Retransplant, Death or Loss to follow-up. Identification of acute rejections was based on the local pathologist's evaluation of endomyocardial biopsy slides. Hemodynamic compromise was present if 1 or more of the following were met: Ejection fraction ≤ 30% or 25% lower than Baseline or Fractional shortening ≤ 20% or 25% lower than Baseline and/or use of inotropic treatment. |
24 Months
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Percentage of Participants With Graft Loss/Re-transplant, Death or Loss to Follow-up at 24 Months
Časové okno: 24 Months
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Loss to follow-up for this composite endpoint included participants who did not experience graft loss/re-transplant or death and whose last day of contact was prior to Day 631 (start day of 24 Month visit window).
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24 Months
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Renal Function Calculated by Glomerular Filtration Rate (GFR) at 24 Months
Časové okno: 24 Months
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GFR was calculated using the Modification of Diet and Renal Disease (MDRD) formula: GFR [mL/min/1.73m^2] = 186.3*(C^-1.154)*(A^-0.203)*G*R C is the serum concentration of creatinine [mg/dL] A is age [years] G=0.742 when gender is female, otherwise G=1 R=1.21 when race is black, otherwise R=1 |
24 Months
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Percentage of Participants With Biopsy-proven Acute Rejection (BPAR of ISHLT Grade ≥ 3A), Acute Rejection (AR) Associated With Hemodynamic Compromise (HDC), Graft Loss/Re-transplant and Death at Month 24
Časové okno: 24 Months
|
Identification of acute rejections was based on the local pathologist's evaluation of endomyocardial biopsy slides. Hemodynamic compromise was present if 1 or more of the following were met: Ejection fraction ≤ 30% or 25% lower than Baseline or Fractional shortening ≤ 20% or 25% lower than Baseline, and/ or use of inotropic treatment. |
24 Months
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Spolupracovníci a vyšetřovatelé
Sponzor
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia
Primární dokončení (Aktuální)
Dokončení studie (Aktuální)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Odhad)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Odhad)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Fyziologické účinky léků
- Molekulární mechanismy farmakologického působení
- Antiinfekční látky
- Inhibitory enzymů
- Antirevmatika
- Antineoplastická činidla
- Imunosupresivní látky
- Imunologické faktory
- Dermatologická činidla
- Antibakteriální látky
- Antibiotika, antineoplastika
- Antifungální látky
- Antituberkulární látky
- Antibiotika, antituberkulo
- Inhibitory kalcineurinu
- Kyselina mykofenolová
- Everolimus
- Cyklosporin
- Cyklosporiny
Další identifikační čísla studie
- CRAD001A2310
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