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OpenTrials
Completed

NCT Number: NCT00300274

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

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.

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Key information

Conditions

Graft Rejection Cardiovascular Diseases Heart Diseases

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Sanatorio Parque, Rosario, Santa Fe Province, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Everolimus

Drug

Everolimus supplied as 0.75 mg tablets. Everolimus was also supplied in 0.25 mg and 0.5 mg tablets for dose adjustments.

Other names: Zortress®, Certican®

Mycophenolate mofetil

Drug

Mycophenolate mofetil supplied as 500 mg tablets.

Other names: Cellcept®

cyclosporine

Drug

Cyclosporine reduced dose in the everolimus arms (approximately half of the standard dose) and standard dose in the mycophenolate mofetil arm.

Other names: Neoral®

Corticosteroids

Drug

Corticosteroids standard dose.

Primary outcomes

  1. Percentage of Participants With Composite Efficacy Failure at 12 Months

    Time frame: 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.

Secondary outcomes

  1. Percentage of Participants With Graft Loss/Re-transplant, Death or Loss to Follow-up at 12 Months

    Time frame: 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).

  2. Renal Function Measured by Glomerular Filtration Rate (GFR) at 12 Months

    Time frame: 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

  3. Change From Baseline in the Average Maximum Intimal Thickness at Month 12

    Time frame: 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.

  4. Percentage of Participants With Cardiac Allograft Vasculopathy (CAV) at Month 12

    Time frame: 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.

  5. 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

    Time frame: 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.

  6. Percentage of Participants With Composite Efficacy Failure at 24 Months

    Time frame: 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.

  7. Percentage of Participants With Graft Loss/Re-transplant, Death or Loss to Follow-up at 24 Months

    Time frame: 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).

  8. Renal Function Calculated by Glomerular Filtration Rate (GFR) at 24 Months

    Time frame: 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

  9. 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

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

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

Important dates

Study start
2006
Primary completion
2011
Study completion
2011
First posted
Mar 8, 2006
Registry last updated
Aug 16, 2012

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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