Efficacy and Safety Study of Supramaximal Titrated Inhibition of RAAS in Idiopathic Dilated Cardiomyopathy
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 480
- 试验地点
- 1
- 主要终点
- All cause death or admission for heart failure
研究概览
简要总结
Dilated cardiomyopathy (DCM) is a poorly understood cause of systolic heart failure and is the most common indication for heart transplantation worldwide. Despite advances in medical and device therapy, the 5-year mortality of patients with DCM remains high.
Patients diagnosed of dilated cardiomyopathy with a NYHA functional class of II to IV and left ventricular ejection fraction(LVEF) <35% were selected for randomized controlled study of the efficacy and safety of high dose Renin-angiotensin system (RAS) inhibitor (benazepril or valsartan), in comparison with low dose RAS inhibitor(benazepril or valsartan) and standard beta-adrenergic blocker therapy (metoprolol). The primary endpoint was all cause death or admission for heart failure. Additional prespecified outcomes included all-cause death, cardiovascular death, all-cause admission, heart failure admission. Secondary cardiovascular outcomes included the changes from baseline to the last available observation after treatment in NYHA functional class, quality-of-life scores, LVEF, LVEDD, mitral regurgitation and wall-motion score index assessed by ECG. Adverse events were reported during in-hospital observation and follow-ups.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of dilated cardiomyopathy
- •Left ventricular ejection fraction < 35%
- •NYHA Functional classes of II-IV
- •Symptomatic but not rapidly deteriorating 1 month before enrollment
- •Signed informed consent
排除标准
- •Contradictions and intolerance of the studied drugs:
- •supine systolic arterial blood pressure < 90 mmHg,
- •renal artery stenosis >50%,
- •pregnancy or lactation,
- •impaired renal function (estimated glomerular filtration rate < 60 ml/min/1.73m2,
- •impaired liver function (total bilirubin >2 times upper limit of normal,
- •serum aspartate AST or alanine ALT >3 times the upper limit of normal),
- •hemoglobin less than 8 mg/dl, hyperkalaemia (serum potassium >5.5mmol/l),
- •obstructive lung disease,
- •advanced atrioventricular block,
- •any co-morbidity with impact on survival, and
- •known intolerance to benazepril, valsartan and metoprolol succinate;
- •HF secondary to a known cause:
- •coronary artery disease based on coronary angiography (≥50% stenosis in ≥1 of the major coronary arteries) and/or a history of myocardial infarction or angina pectoris,
- •acute or subacute stage of myocarditis,
- •primary valve disease,
- •diabetes mellitus,
- •excessive use of alcohol or illicit drugs;
- •Expected or performed cardiac resynchronization therapy and heart transplantation.
研究组 & 干预措施
High dose Benazepril
Patients randomized to high-dose benazepril were started on benazepril 10mg twice daily, and uptitrated to target doses within 7 days under in-hospital observation. The target high doses of benazepril is determined by left-ventricular end-diastolic diameter (LVEDD) (the maximal value of anteroposterior and lateral diameters) obtained by ECG at the randomization visit. A target dose of benazepril 40mg, 60mg, 80mg daily were assigned to patients with LVEDD of 50-59, 60-69, ≥70 mm respectively.
干预措施: Benazepril (Drug)
Metoprolol
Patients in the metoprolol group were started on 11.875-23.75mg of metoprolol succinct extended-release tablet once daily (11.875mg was recommended for patients with NYHA functional classes III-IV), and then doses were doubled every 2 weeks to achieve asymptomatic bradycardia (50-60 bpm of heart rate) over 4-6 weeks. Investigators were encouraged to up-titrate metoprolol to a maximum dose of 190mg whenever possible.
干预措施: Metoprolol (Drug)
Low-dose valsartan
Patients randomized to low dose valsartan receive valsartan 80 mg until study completion.
干预措施: Valsartan (Drug)
Low dose Benazepril
Patients randomized to low dose Benazepril receive Benazepril 10 mg until study completion.
干预措施: Benazepril (Drug)
High dose valsartan
Patients randomized to high-dose valsartan were started on valsartan 80mg twice daily, and uptitrated to target doses within 7 days under in-hospital observation. The target high doses of valsartan is determined by left-ventricular end-diastolic diameter (LVEDD) (the maximal value of anteroposterior and lateral diameters) obtained by ECG at the randomization visit. A target dose of valsartan 320mg, 480mg, 640mg daily were assigned to patients with LVEDD of 50-59, 60-69, ≥70 mm respectively.
干预措施: Valsartan (Drug)
结局指标
主要结局
All cause death or admission for heart failure
时间窗: 48 months after enrollment
Admission for heart failure was defined as a minimum of 24 h inpatient admission to any health-care facility, with the primary cause being treated for worsening heart failure and during which an additional diuretic drug, intravenous or oral nitrate, or intravenous inotropic agent was given.
次要结局
- Left-ventricular end-diastolic diameter(6, 12 , 24 and 36 months after enrollment)
- Left-ventricular ejection fraction(6,12, 24 and 36 months after enrollment)
- Changes in NYHA functional class(6,12, 24 and 36 months after enrollment)
研究者
Hezheng
Professor
Xijing Hospital