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Efficacy and Safety of Everolimus in Recipients of Heart Transplants to Prevent Acute and Chronic Rejection

10 luglio 2012 aggiornato da: Novartis Pharmaceuticals

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

This trial was to examine the impact of everolimus and reduced dose of cyclosporine on efficacy and safety compared to mycophenolate mofetil and a standard dose of cyclosporine in heart transplant recipients.

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Tipo di studio

Interventistico

Iscrizione (Effettivo)

721

Fase

  • Fase 3

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Argentina
      • Buenos Aires, Argentina
        • Fundacion Favalaro
    • Santa Fe
      • Rosario, Santa Fe, Argentina
        • Sanatorio Parque
  • Australia
    • New South Wales
      • Darlinghurst, New South Wales, Australia
        • St Vincents Hospital
    • Queensland
      • Chermside, Queensland, Australia
        • Prince Charles Hospital
    • Western Australia
      • Perth, Western Australia, Australia
        • Royal Perth Hospital
  • Austria
      • Vienna, Austria
        • Universitaet Wien
  • Belgio
      • Bruxelles, Belgio
        • Cliniques Universitaires Saint-Luc
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada
        • University of Alberta Hospital
    • British Columbia
      • Vancouver, British Columbia, Canada
        • St Paul's Hospital
    • Nova Scotia
      • Halifax, Nova Scotia, Canada
        • New Halifax Infirmary
    • Ontario
      • Toronto, Ontario, Canada
        • Toronto General Hospital
    • Quebec
      • Sainte-Foy, Quebec, Canada
        • Institut Univ. de cardiologie et pneumologie de Quebec
  • Francia
      • Lyon, Francia
        • Hopital Cardiologique de Lyon
      • Paris, Francia
        • Hopital Pitie Salpetriere
      • Paris, Francia
        • Hopital Georges Pompidou
      • Strasbourg, Francia
        • CHU de Strasbourg Hopital Civil Medicale B
      • Vandoeuvre les Nancy, Francia
        • CHU Hopital de Brabois
  • Germania
      • Bad Oeynhausen, Germania
        • Herz- u. Diabeteszentrum NRW/Ruhr-Univ. Bochum
      • Berlin, Germania
        • Deutsches Herzzentrum Berlin
      • Hamburg, Germania
        • Universitaetsklinikum Hamburg-Eppendorf
      • Hannover, Germania
        • Kliniken der Med. Hochschule
      • Kiel, Germania
        • Universitaetsklinikum Kiel
      • Regensburg, Germania
        • Universitaetsklinik Regensburg
  • Italia
      • Bologna, Italia
        • Az. Osp. di Bologna Policl. S. Orsola-Malpighi Univ. degli Studi
      • Cagliari, Italia
        • Azienda Ospedaliera G. Brotzu
      • Padova, Italia
        • A.O.-Universita di Padova-Universita degli Studi
      • Pavio, Italia
        • Fodazione IRCCS Policlinico S. Matteo
      • Roma, Italia
        • Azienda Ospedaliera S. Camillo-Forlanini
      • Torino, Italia
        • Az. Ospedaliero-Universitaria S. Giovanni Battista di Torino
  • Norvegia
      • Oslo, Norvegia
        • Rikshospitalet, Hjertemedisinskavdeling
  • Nuova Zelanda
      • Auckland, Nuova Zelanda
        • Auckland Hospital
  • Porto Rico
      • San Juan, Porto Rico
        • Cardiovascular Center of Puerto Rico and the Caribbean
  • Regno Unito
      • Birmingham, Regno Unito
        • Queen Elizabeth Hospital
      • Cambridge, Regno Unito
        • Papworth Hospital
      • Manchester, Regno Unito
        • Wythenshawe Hospital
  • Spagna
      • Cordoba, Spagna
        • Hospital Universitario Reina Sofia
      • Madrid, Spagna
        • Hospital Puerta de Hierro Majadahonda
  • Stati Uniti
    • California
      • Los Angeles, California, Stati Uniti
        • UCLA Medical Center
      • San Francisco, California, Stati Uniti
        • California Pacific Medical Center
      • Stanford, California, Stati Uniti
        • Stanford U Sch, Falk Cardiovasular Research Ctr.
    • Florida
      • Gainesville, Florida, Stati Uniti
        • University of Florida Shands Hospital
    • Georgia
      • Atlanta, Georgia, Stati Uniti
        • Emory University Hospital
    • Illinois
      • Maywood, Illinois, Stati Uniti
        • Loyola Univerisity Medical School
    • Massachusetts
      • Boston, Massachusetts, Stati Uniti
        • Massachusetts General Hospital
      • Boston, Massachusetts, Stati Uniti
        • Tufts Medical Center
    • Michigan
      • Ann Arbor, Michigan, Stati Uniti
        • University of Michigan Health System
    • Missouri
      • St. Louis, Missouri, Stati Uniti
        • Washington University School of Medicine
    • New York
      • New York, New York, Stati Uniti
        • Columbia University Medical Center
      • New York, New York, Stati Uniti
        • Recanati Miller Transplant Institute
    • North Carolina
      • Chapel Hill, North Carolina, Stati Uniti
        • UNC Division of Cardiology
      • Durham, North Carolina, Stati Uniti
        • Duke University Heart Failure Research
    • Ohio
      • Cleveland, Ohio, Stati Uniti
        • Cleveland Clinic Foundation
    • Pennsylvania
      • Hershey, Pennsylvania, Stati Uniti
        • Penn State College of Medicine
      • Philadelphia, Pennsylvania, Stati Uniti
        • Temple University Hospital
      • Philadelphia, Pennsylvania, Stati Uniti
        • Thomas Jefferson University Hospital
      • Philadelphia, Pennsylvania, Stati Uniti
        • Hahnemann University Hospital
    • South Carolina
      • Charleston, South Carolina, Stati Uniti
        • Medical University of South Carolina
    • Texas
      • Austin, Texas, Stati Uniti
        • Texas Cardiovascular Consultants
      • Galveston, Texas, Stati Uniti
        • University of Texas Medical Branch, Div of Cardio Thoracic
      • Houston, Texas, Stati Uniti, 77030
        • Methodist Hospital/DeBakey Heart Failure Research Center
    • Utah
      • Murray, Utah, Stati Uniti
        • Intermountain Medical Center
    • Wisconsin
      • Madison, Wisconsin, Stati Uniti, 53792
        • University of Wisconsin - Madison Medical School
      • Milwakee, Wisconsin, Stati Uniti
        • St. Luke's Medical Center Cardiac Services
  • Taiwan
      • Taipei, Taiwan
        • National Taiwan University Hospital

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 18 anni a 70 anni (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: 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.
Droga: everolimus
Everolimus supplied as 0.75 mg tablets. Everolimus was also supplied in 0.25 mg and 0.5 mg tablets for dose adjustments.
Altri nomi:
  • Certican®
  • Zortress®
Droga: cyclosporine
Cyclosporine reduced dose in the everolimus arms (approximately half of the standard dose) and standard dose in the mycophenolate mofetil arm.
Altri nomi:
  • Neoral®
Droga: corticosteroids
Corticosteroids standard dose.
Sperimentale: 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.
Droga: everolimus
Everolimus supplied as 0.75 mg tablets. Everolimus was also supplied in 0.25 mg and 0.5 mg tablets for dose adjustments.
Altri nomi:
  • Certican®
  • Zortress®
Droga: cyclosporine
Cyclosporine reduced dose in the everolimus arms (approximately half of the standard dose) and standard dose in the mycophenolate mofetil arm.
Altri nomi:
  • Neoral®
Droga: corticosteroids
Corticosteroids standard dose.
Comparatore attivo: 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.
Droga: cyclosporine
Cyclosporine reduced dose in the everolimus arms (approximately half of the standard dose) and standard dose in the mycophenolate mofetil arm.
Altri nomi:
  • Neoral®
Droga: corticosteroids
Corticosteroids standard dose.
Droga: mycophenolate mofetil
Mycophenolate mofetil supplied as 500 mg tablets.
Altri nomi:
  • Cellcept®

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Percentage of Participants With Composite Efficacy Failure at 12 Months
Lasso di tempo: 12 Months

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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Percentage of Participants With Graft Loss/Re-transplant, Death or Loss to Follow-up at 12 Months
Lasso di tempo: 12 Months
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).
12 Months
Renal Function Measured by Glomerular Filtration Rate (GFR) at 12 Months
Lasso di tempo: 12 Months

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
Change From Baseline in the Average Maximum Intimal Thickness at Month 12
Lasso di tempo: Baseline, Month 12
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.
Baseline, Month 12
Percentage of Participants With Cardiac Allograft Vasculopathy (CAV) at Month 12
Lasso di tempo: 12 Months
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.
12 Months
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
Lasso di tempo: 12 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.
12 Months
Percentage of Participants With Composite Efficacy Failure at 24 Months
Lasso di tempo: 24 Months

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
Percentage of Participants With Graft Loss/Re-transplant, Death or Loss to Follow-up at 24 Months
Lasso di tempo: 24 Months
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).
24 Months
Renal Function Calculated by Glomerular Filtration Rate (GFR) at 24 Months
Lasso di tempo: 24 Months

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
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
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Novartis Pharmaceuticals

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 gennaio 2006

Completamento primario (Effettivo)

1 luglio 2011

Completamento dello studio (Effettivo)

1 luglio 2011

Date di iscrizione allo studio

Primo inviato

6 marzo 2006

Primo inviato che soddisfa i criteri di controllo qualità

6 marzo 2006

Primo Inserito (Stima)

8 marzo 2006

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Stima)

16 agosto 2012

Ultimo aggiornamento inviato che soddisfa i criteri QC

10 luglio 2012

Ultimo verificato

1 luglio 2012

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • CRAD001A2310

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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