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
研究概览
研究类型
注册 (实际的)
阶段
- 第三阶段
联系人和位置
学习地点
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Alberta
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Edmonton、Alberta、加拿大
- University of Alberta Hospital
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British Columbia
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Vancouver、British Columbia、加拿大
- St Paul's Hospital
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Nova Scotia
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Halifax、Nova Scotia、加拿大
- New Halifax Infirmary
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Ontario
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Toronto、Ontario、加拿大
- Toronto General Hospital
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Quebec
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Sainte-Foy、Quebec、加拿大
- Institut Univ. de cardiologie et pneumologie de Quebec
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Taipei、台湾
- National Taiwan University Hospital
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Vienna、奥地利
- Universitaet Wien
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Bad Oeynhausen、德国
- Herz- u. Diabeteszentrum NRW/Ruhr-Univ. Bochum
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Berlin、德国
- Deutsches Herzzentrum Berlin
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Hamburg、德国
- Universitaetsklinikum Hamburg-Eppendorf
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Hannover、德国
- Kliniken der Med. Hochschule
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Kiel、德国
- Universitaetsklinikum Kiel
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Regensburg、德国
- Universitaetsklinik Regensburg
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Bologna、意大利
- Az. Osp. di Bologna Policl. S. Orsola-Malpighi Univ. degli Studi
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Cagliari、意大利
- Azienda Ospedaliera G. Brotzu
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Padova、意大利
- A.O.-Universita di Padova-Universita degli Studi
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Pavio、意大利
- Fodazione IRCCS Policlinico S. Matteo
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Roma、意大利
- Azienda Ospedaliera S. Camillo-Forlanini
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Torino、意大利
- Az. Ospedaliero-Universitaria S. Giovanni Battista di Torino
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Oslo、挪威
- Rikshospitalet, Hjertemedisinskavdeling
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Auckland、新西兰
- Auckland Hospital
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Bruxelles、比利时
- Cliniques Universitaires Saint-Luc
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Lyon、法国
- Hopital Cardiologique de Lyon
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Paris、法国
- Hôpital Pitié Salpêtrière
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Paris、法国
- Hopital Georges Pompidou
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Strasbourg、法国
- CHU de Strasbourg Hopital Civil Medicale B
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Vandoeuvre les Nancy、法国
- CHU Hopital de Brabois
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San Juan、波多黎各
- Cardiovascular Center of Puerto Rico and the Caribbean
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New South Wales
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Darlinghurst、New South Wales、澳大利亚
- St Vincents Hospital
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Queensland
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Chermside、Queensland、澳大利亚
- Prince Charles Hospital
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Western Australia
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Perth、Western Australia、澳大利亚
- Royal Perth Hospital
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California
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Los Angeles、California、美国
- UCLA Medical Center
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San Francisco、California、美国
- California Pacific Medical Center
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Stanford、California、美国
- Stanford U Sch, Falk Cardiovasular Research Ctr.
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Florida
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Gainesville、Florida、美国
- University of Florida Shands Hospital
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Georgia
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Atlanta、Georgia、美国
- Emory University Hospital
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Illinois
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Maywood、Illinois、美国
- Loyola Univerisity Medical School
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Massachusetts
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Boston、Massachusetts、美国
- Massachusetts General hospital
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Boston、Massachusetts、美国
- Tufts Medical Center
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Michigan
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Ann Arbor、Michigan、美国
- University of Michigan Health System
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Missouri
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St. Louis、Missouri、美国
- Washington University School of Medicine
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New York
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New York、New York、美国
- Columbia University Medical Center
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New York、New York、美国
- Recanati Miller Transplant Institute
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North Carolina
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Chapel Hill、North Carolina、美国
- UNC Division of Cardiology
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Durham、North Carolina、美国
- Duke University Heart Failure Research
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Ohio
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Cleveland、Ohio、美国
- Cleveland Clinic Foundation
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Pennsylvania
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Hershey、Pennsylvania、美国
- Penn State College of Medicine
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Philadelphia、Pennsylvania、美国
- Temple University Hospital
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Philadelphia、Pennsylvania、美国
- Thomas Jefferson University Hospital
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Philadelphia、Pennsylvania、美国
- Hahnemann University Hospital
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South Carolina
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Charleston、South Carolina、美国
- Medical University of South Carolina
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Texas
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Austin、Texas、美国
- Texas Cardiovascular Consultants
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Galveston、Texas、美国
- University of Texas Medical Branch, Div of Cardio Thoracic
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Houston、Texas、美国、77030
- Methodist Hospital/DeBakey Heart Failure Research Center
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Utah
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Murray、Utah、美国
- Intermountain Medical Center
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Wisconsin
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Madison、Wisconsin、美国、53792
- University of Wisconsin - Madison Medical School
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Milwakee、Wisconsin、美国
- St. Luke's Medical Center Cardiac Services
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Birmingham、英国
- Queen Elizabeth Hospital
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Cambridge、英国
- Papworth Hospital
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Manchester、英国
- Wythenshawe Hospital
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Cordoba、西班牙
- Hospital Universitario Reina Sofia
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Madrid、西班牙
- Hospital Puerta de Hierro Majadahonda
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Buenos Aires、阿根廷
- Fundacion Favalaro
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Santa Fe
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Rosario、Santa Fe、阿根廷
- Sanatorio Parque
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
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.
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：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.
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Everolimus supplied as 0.75 mg tablets.
Everolimus was also supplied in 0.25 mg and 0.5 mg tablets for dose adjustments.
其他名称：
Cyclosporine reduced dose in the everolimus arms (approximately half of the standard dose) and standard dose in the mycophenolate mofetil arm.
其他名称：
Corticosteroids standard dose.
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实验性的：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.
其他名称：
Cyclosporine reduced dose in the everolimus arms (approximately half of the standard dose) and standard dose in the mycophenolate mofetil arm.
其他名称：
Corticosteroids standard dose.
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有源比较器：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.
其他名称：
Corticosteroids standard dose.
Mycophenolate mofetil supplied as 500 mg tablets.
其他名称：
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Percentage of Participants With Composite Efficacy Failure at 12 Months
大体时间：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
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Percentage of Participants With Graft Loss/Re-transplant, Death or Loss to Follow-up at 12 Months
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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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合作者和调查者
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.
everolimus的临床试验
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Universitaire Ziekenhuizen KU Leuven完全的