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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
721
Everolimus supplied as 0.75 mg tablets. Everolimus was also supplied in 0.25 mg and 0.5 mg tablets for dose adjustments.
Mycophenolate mofetil supplied as 500 mg tablets.
Cyclosporine reduced dose in the everolimus arms (approximately half of the standard dose) and standard dose in the mycophenolate mofetil arm.
Percentage of Participants With Composite Efficacy Failure at 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.
Time frame: 12 Months
Percentage of Participants With Graft Loss/Re-transplant, Death or Loss to Follow-up at 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).
Time frame: 12 Months
Renal Function Measured by Glomerular Filtration Rate (GFR) at 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
Time frame: 12 Months
Change From Baseline in the Average Maximum Intimal Thickness at 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.
Time frame: Baseline, Month 12
Percentage of Participants With Cardiac Allograft Vasculopathy (CAV) at Month 12
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Corticosteroids standard dose.
UCLA Medical Center
Los Angeles, California, United States
California Pacific Medical Center
San Francisco, California, United States
Stanford U Sch, Falk Cardiovasular Research Ctr.
Stanford, California, United States
University of Florida Shands Hospital
Gainesville, Florida, United States
Emory University Hospital
Atlanta, Georgia, United States
Loyola Univerisity Medical School
Maywood, Illinois, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Tufts Medical Center
Boston, Massachusetts, United States
University of Michigan Health System
Ann Arbor, Michigan, United States
Washington University School of Medicine
St Louis, Missouri, United States
...and 54 more locations
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.
Time frame: 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
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.
Time frame: 12 Months
Percentage of Participants With Composite Efficacy Failure at 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.
Time frame: 24 Months
Percentage of Participants With Graft Loss/Re-transplant, Death or Loss to Follow-up at 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).
Time frame: 24 Months
Renal Function Calculated by Glomerular Filtration Rate (GFR) at 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
Time frame: 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
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.
Time frame: 24 Months