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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00300274
First received: March 6, 2006
Last updated: July 10, 2012
Last verified: July 2012

March 6, 2006
July 10, 2012
January 2006
July 2011   (final data collection date for primary outcome measure)
Percentage of Participants With Composite Efficacy Failure at 12 Months [ Time Frame: 12 Months ] [ Designated as safety issue: No ]

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.

Not Provided
Complete list of historical versions of study NCT00300274 on ClinicalTrials.gov Archive Site
  • Percentage of Participants With Graft Loss/Re-transplant, Death or Loss to Follow-up at 12 Months [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
    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).
  • Renal Function Measured by Glomerular Filtration Rate (GFR) at 12 Months [ Time Frame: 12 Months ] [ Designated as safety issue: Yes ]

    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

  • Change From Baseline in the Average Maximum Intimal Thickness at Month 12 [ Time Frame: Baseline, Month 12 ] [ Designated as safety issue: No ]
    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.
  • Percentage of Participants With Cardiac Allograft Vasculopathy (CAV) at Month 12 [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
    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.
  • 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 ] [ Designated as safety issue: No ]

    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.

  • Percentage of Participants With Composite Efficacy Failure at 24 Months [ Time Frame: 24 Months ] [ Designated as safety issue: No ]

    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.

  • Percentage of Participants With Graft Loss/Re-transplant, Death or Loss to Follow-up at 24 Months [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
    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).
  • Renal Function Calculated by Glomerular Filtration Rate (GFR) at 24 Months [ Time Frame: 24 Months ] [ Designated as safety issue: Yes ]

    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

  • 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 ] [ Designated as safety issue: No ]

    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.

Not Provided
Not Provided
Not Provided
 
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

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Graft Rejection
  • Drug: everolimus
    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®
  • Drug: mycophenolate mofetil
    Mycophenolate mofetil supplied as 500 mg tablets.
    Other Name: Cellcept®
  • Drug: cyclosporine
    Cyclosporine reduced dose in the everolimus arms (approximately half of the standard dose) and standard dose in the mycophenolate mofetil arm.
    Other Name: Neoral®
  • Drug: corticosteroids
    Corticosteroids standard dose.
  • Experimental: 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.
    Interventions:
    • Drug: everolimus
    • Drug: cyclosporine
    • Drug: corticosteroids
  • Experimental: 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.

    Interventions:
    • Drug: everolimus
    • Drug: cyclosporine
    • Drug: corticosteroids
  • Active Comparator: 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.
    Interventions:
    • Drug: mycophenolate mofetil
    • Drug: cyclosporine
    • Drug: corticosteroids
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
721
July 2011
July 2011   (final data collection date for primary outcome measure)

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.

Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Australia,   Austria,   Belgium,   Canada,   France,   Germany,   Italy,   New Zealand,   Norway,   Puerto Rico,   Spain,   Taiwan,   United Kingdom
 
NCT00300274
CRAD001A2310
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Novartis
Novartis
July 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP