A 36-week, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study Including a 2 Year Extension Study to Evaluate Efficacy and Safety of Aliskiren on the Prevention of Left Ventricular Remodeling in High Risk Post-acute Myocardial Infarction Patients When Added to Optimized Standard Therapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Novartis
- 入组人数
- 820
- 试验地点
- 23
- 主要终点
- Core Study: Change From Baseline in Left Ventricular End Systolic Volume (LVESV) as Measured by Echocardiography at End of Study.
研究概览
简要总结
The core and extension studies assessed the safety and efficacy of aliskiren when added to optimized standard therapy in patients that have had a high risk acute myocardial infarction (heart attack).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients 18 years and older.
- •Patients within 7-42 days of an acute myocardial infarction associated with left ventricular systolic dysfunction.
- •Documented left ventricular systolic dysfunction associated with the qualifying acute myocardial.
- •Patients must be on stable doses of the following concomitant medications for at least 2 weeks prior to Visit 1 unless contraindicated due to intolerance:
- •A Beta-blocker
- •An Anti-platelet agent
- •An evidence-based dose of an Angiotensin Converting Enzyme Inhibitor (ACEI) or Angiotensin Receptor Blocker (ARB) but not both.
- •Qualifying Echocardiogram at Visit 1:
排除标准
- •Patients requiring both Angiotensin Converting Enzyme Inhibitor (ACEI) and Angiotensin Receptor Blocker (ARB) combination therapy at V1 or any time during the study.
- •Severe refractory hypertension defined as mean sitting systolic blood pressure (MSSBP) ≥ 180 mmHg and/or mean sitting diastolic blood pressure (MSDBP) ≥ 110 mmHg) at Visit
- •Cardiogenic shock or systolic BP < 100 mmHg or diastolic < 60 mmHg within the 24 hours prior to Visits 1 or 2
- •Estimated Glomerular Filtration Rate (eGFR) < 30 ml/min/1.73m2 using the MDRD formula at Visit
- •Stroke or transient ischemic event (TIA) within 6 months of Study Visit 1
- •Extension Study Inclusion Criteria:
- •Male or female patients who completed the core study through Visit 10 while on double-blind study drug
- •Patients who were able to participate in the study, and who consented to do so after the purpose and nature of the study had been clearly explained to them (written informed consent)
- •Extension Study Exclusion Criteria:
- •New York Heart Association (NYHA) class IV Congestive Heart Failure at Visit 1 (Core study Visit 10)
- •Symptomatic hypotension or reported systolic blood pressure (BP) < 90 mmHg within 24 hours prior to Visit 1 (Core study Visit 10)
- •Known Estimated Glomerular Filtration Rate (eGFR) < 30 mL/min/1.73m^2 using the Modification of Diet in Renal Disease (MDRD) formula at Visit 1 (Core study Visit 10)
- •Pregnant or nursing (lactating) women, where pregnancy was defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL)
- •Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant Unless post-menopausal or using an acceptable method of contraception
- •Any surgical or medical condition that in the opinion of the investigator may place the patient at higher risk from his/her participation in the study or was likely to prevent the patient from complying with the requirements or completing the study
- •Other protocol-defined inclusion/exclusion criteria applied
研究组 & 干预措施
Aliskiren
Core Study: Aliskiren ascending doses: 75 mg tablet for 1st week, 150 mg for 2nd week, 300 mg for next 34 weeks orally once daily in the morning.
Extension Study: Patients from both the core arms who completed core study and signed informed consent form were included in this arm of extension study.
Patients received 150 mg aliskiren tablet orally once a day for two weeks. Patients were then up-titrated to 300 mg aliskiren orally once a day at the discretion of the principal investigator based on their clinical condition for the duration of the study.
干预措施: Aliskiren (Drug)
placebo
Core study: placebo for 36 weeks once daily in the morning
干预措施: placebo (Drug)
结局指标
主要结局
Core Study: Change From Baseline in Left Ventricular End Systolic Volume (LVESV) as Measured by Echocardiography at End of Study.
时间窗: Baseline and final visit (after 26 to 36 weeks of treatment)
Change from baseline to end of study in left ventricular end systolic volume (LVESV) as measured by echocardiography. LVESV is a measurement of the volume of blood in the heart's left ventricular chamber at the end of the heart's contraction. This measurement was made by the echocardiography lab. LVESV values between 22 to 58 mL for men and 19-49 mL for women are considered normal. Baseline LVESV was a covariate.
Extension Study: Percentage of Participants With Deaths, Serious Adverse Events (SAEs), Discontinuation for Adverse Events (AEs) and Discontinuations for Abnormal Lab Values
时间窗: Extension study (24 weeks)
AEs are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
次要结局
- Core Study: Time to First Occurrence for the Composite Endpoints of Echocardiogram and Adjudicated Outcomes(LVEF was measured at baseline and at final visit (after 26 to 36 weeks of treatment). Other endpoint components were assessed from randomization until the end of the study (week 36).)
- Core Study: Change From Baseline in Left Ventricular End Diastolic Volume (LVEDV)(Baseline and final visit (after 26 to 36 weeks of treatment))
- Core Study: Change From Baseline in Left Ventricular Ejection Fraction (LVEF)(Baseline and final visit (after 26 to 36 weeks of treatment ))
- Core Study: Change From Baseline to End of Study in Infarction Segment Length (ISL) as Measured by Echocardiography(Baseline and final visit (after 26 to 36 weeks of treatment))
- Core Study: Change From Baseline to End of Study in Wall Motion Score (WMS) as Measured by Echocardiography(Baseline and final visit (after 26 to 36 weeks of treatment))
- Extension Study: Change From Baseline in Left Ventricular End Systolic Volume (LVESV) at Month 12(Baseline(extension study), Month 12 (extension study))
- Extension Study: Change From Baseline in Left Ventricular End Diastolic Volume (LVEDV) at Month 12(Baseline (extension study), Month 12 (extension study))
- Extension Study: Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Month 12(Baseline(extension study), Month 12 (extension study))
- Extension Study: Percentage of Participants With Orthostatic Blood Pressure Change(Baseline (Day 0 Extension study), Week 2, Months 1, 3, 6, 9,16, 20, 24)
- Extension Study: Percentage of Participants With Specified Criteria in Selected Labs by Laboratory Parameter(24 Months)