A Multicenter, Randomized, Double-blind, Parallel Group, Active-controlled Study to Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality in Patients With Chronic Heart Failure and Reduced Ejection Fraction
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 8,442
- 试验地点
- 1
- 主要终点
- Number of Participants That Had First Occurrence of the Composite Endpoint, Which is Defined as Either Cardiovascular (CV) Death or Heart Failure (HF) Hospitalization
研究概览
简要总结
The study will evaluate the efficacy and safety of LCZ696 compared to enalapril on morbidity and mortality in patients with chronic heart failure (NYHA Class II - IV and EF =< 35%).
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
- •Patients must give written informed consent before any assessment is performed.
- •Outpatients ≥ 18 years of age, male or female.
- •Patients with a diagnosis of CHF NYHA class II-IV and reduced ejection fraction (EF =< 35%) and elevated BNP.
- •Patients must be on an ACEI or an ARB at a stable dose of at least enalapril 10 mg/d or equivalent for at least 4 weeks.
- •Patients must be treated with a β-blocker, unless contraindicated or not tolerated, at a stable dose for at least 4 weeks.
排除标准
- •Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer.
- •History of hypersensitivity or allergy to any of the study drugs, drugs of similar chemical classes, ACEIs, ARBs, or NEP inhibitors as well as known or suspected contraindications to the study drugs.
- •Previous history of intolerance to recommended target doses of ACEIs or ARBs
- •Known history of angioedema.
- •Requirement of treatment with both ACEIs and ARBs.
- •Current acute decompensated HF (exacerbation of chronic HF manifested by signs and symptoms that may require intravenous therapy).
- •Symptomatic hypotension and/or a SBP < 100 mmHg.
- •Estimated GFR < 30 mL/min/1.73m2 as measured by the simplified MDRD formula
- •Serum potassium > 5.2 mmol/L.
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
LCZ696
single-blind active run-in period consisted of treatment with enalapril 10 mg bid, followed by LCZ696 100 mg bid, and then LCZ696 200 mg bid over a total duration of 5 to 10 weeks. Temporary down-titration from LCZ696 200 mg bid to LCZ696 100 mg bid was allowed provided the patient was up-titrated back to LCZ696 200 mg bid and tolerated this dose for at least two weeks before being eligible for randomization. LCZ696 200mg BID during double blind treatment period
干预措施: LCZ696 200 mg BID (Drug)
Enalapril
single-blind active run-in period consisted of treatment with enalapril 10 mg bid, followed by LCZ696 100 mg bid, and then LCZ696 200 mg bid over a total duration of 5 to 10 weeks. Temporary down-titration from LCZ696 200 mg bid to LCZ696 100 mg bid was allowed provided the patient was up-titrated back to LCZ696 200 mg bid and tolerated this dose for at least two weeks before being eligible for randomization. Enalapril 10 mg BID during double blind treatment period
干预措施: Enalapril 10 mg BID (Drug)
结局指标
主要结局
Number of Participants That Had First Occurrence of the Composite Endpoint, Which is Defined as Either Cardiovascular (CV) Death or Heart Failure (HF) Hospitalization
时间窗: up to 51 months
Number of participants that had first occurrence of the composite endpoint, which is defined as either CV death or HF hospitalization due to HF.
次要结局
- Number of Patients - All-cause Mortality(up to 51 months)
- Number of Patients Reported With Adjudicated Primary Causes of Death(up to 51 months)
- Change From Baseline to Month 8 for the Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score(Baseline, Month 8)
- Number of Patients With First Confirmed Renal Dysfunction(up to 51 months)
- Percentage of Participants With New Onset of Atrial Fibrillation (AF)(up to 51 months)