A Multicenter, Randomized, Double-blind, Double Dummy, Parallel Group, Active-controlled 8-week Study to Evaluate the Effect of Sacubitril/Valsartan (LCZ696) Versus Enalapril on Changes in NT-proBNP and Safety and Tolerability of In-hospital Initiation of LCZ696 Compared to Enalapril in HFrEF Patients Who Have Been Stabilized Following Hospitalization for Acute Decompensated Heart Failure (ADHF).
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 887
- 试验地点
- 1
- 主要终点
- N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) Values and Time-averaged Change From Baseline
研究概览
简要总结
The purpose of this study was to assess the effect of in-hospital initiation of sacubitril/valsartan (LCZ696) vs. enalapril on time averaged proportional change in NT-proBNP in patients who have been stabilized following hospitalization for acute decompensated heart failure (ADHF) and reduced ejection fraction (left ventricular ejection fraction (LVEF) ≤ 40%).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Possess the capacity to provide written informed consent which must be obtained before any assessment is performed.
- •Currently hospitalized for ADHF. Patients with a diagnosis of acute heart failure had to have symptoms and signs of fluid overload (i.e. jugular venous distention, edema or rales on auscultation or pulmonary congestion on chest x-ray) at time of hospitalization.
- •Eligible patients will be randomized no earlier than 24 hours and up to ten days after presentation while still hospitalized as long as meet the following definition of stable status:
- •SBP ≥100mm Hg for the preceding 6 hours prior to randomization; no symptomatic hypotension
- •No increase (intensification) in i.v. diuretic dose within last 6 hours prior to randomization
- •No i.v. inotropic drugs for 24 hours prior to randomization
- •No i.v. vasodilators including nitrates within last 6 hours prior to randomization
- •LVEF ≤40% within the past 6 months (including current hospitalization) using echocardiography, multi gated acquisition scan (MUGA), CT scanning, MRI or ventricular angiography, provided no subsequent study documented an EF of >40%.
- •Elevated NT-proBNP ≥ 1600pg/mL OR BNP ≥400 pg/mL during current hospitalization.
排除标准
- •Currently taking sacubitril/valsartan tablets or any use within the past 30 days.
- •Enrollment in any other clinical trial involving an investigational agent or investigational device.
- •History of hypersensitivity, known or suspected contraindications, or intolerance to any of the study drugs, including ACEIs, ARBs, or Sacubitril (NEP inhibitor).
- •Patients with a known history of angioedema related to previous ACE inhibitor or ARB therapy.
- •Requirement of treatment with both ACE inhibitor and ARB.
- •eGFR < 30 ml/min/1.73 m2 as measured by the simplified Modification of Diet in Renal Disease (MDRD) formula at screening.
- •Serum potassium > 5.2 mEq/L at screening.
- •Known hepatic impairment (as evidenced by total bilirubin > 3 mg/dL, or increased ammonia levels, if performed), or history of cirrhosis with evidence of portal hypertension such as varices
- •Acute coronary syndrome, stroke, transient ischemic attack; cardiac, carotid or other major CV surgery; percutaneous coronary intervention (PCI) or carotid angioplasty, within one month prior to Visit
- •Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
- •Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they are using two birth control methods.
研究组 & 干预措施
sacubitril/valsartan (LCZ696)
Initial dose for patients randomized to sacubitril/valsartan (LCZ696) was determined by the blood pressure at the time of randomization. Study treatment was titrated to the target dose of sacubitril/valsartan (LCZ696) 97/103 mg bid (Dose Level 3). Titration was based on blood pressure at the time of the visit. Dose adjustments were only allowed if indicated per protocol defined safety and tolerability criteria and investigator judgement.
Patients were required to take a total of two tablets twice daily (one tablet of active sacubitril and valsartan and one tablet of enalapril matching placebo pack).
干预措施: sacubitril/valsartan (LCZ696) (Drug)
sacubitril/valsartan (LCZ696)
Initial dose for patients randomized to sacubitril/valsartan (LCZ696) was determined by the blood pressure at the time of randomization. Study treatment was titrated to the target dose of sacubitril/valsartan (LCZ696) 97/103 mg bid (Dose Level 3). Titration was based on blood pressure at the time of the visit. Dose adjustments were only allowed if indicated per protocol defined safety and tolerability criteria and investigator judgement.
Patients were required to take a total of two tablets twice daily (one tablet of active sacubitril and valsartan and one tablet of enalapril matching placebo pack).
干预措施: enalapril matching placebo (Drug)
Enalapril
Initial dose for patients randomized to enalapril were determined by the blood pressure at the time of randomization. Study treatment were titrated to the target dose of enalapril 10 mg bid. Titration were based on blood pressure at the time of the visit. Dose adjustments were only allowed if indicated per protocol defined safety and tolerability criteria and investigator judgement.
Patients were required to take a total of two tablets twice daily (one tablet of active enalapril, second from sacubitril and valsartan matching placebo pack)
干预措施: Enalapril (Drug)
Enalapril
Initial dose for patients randomized to enalapril were determined by the blood pressure at the time of randomization. Study treatment were titrated to the target dose of enalapril 10 mg bid. Titration were based on blood pressure at the time of the visit. Dose adjustments were only allowed if indicated per protocol defined safety and tolerability criteria and investigator judgement.
Patients were required to take a total of two tablets twice daily (one tablet of active enalapril, second from sacubitril and valsartan matching placebo pack)
干预措施: sacubitril/valsartan (LCZ696) matching placebo (Drug)
结局指标
主要结局
N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) Values and Time-averaged Change From Baseline
时间窗: Baseline, Week 4 and Week 8
To assess the effect of in-hospital initiation of sacubitril/valsartan vs. enalapril on the time-averaged percentage change of NT-proBNP from baseline in patients who have been stabilized following hospitalization for ADHF and reduced ejection fraction (left ventricular ejection fraction \[LVEF\] ≤ 40%) between week 4 and 8. Number of patients with both a baseline value and a value at Week 4 or Week 8. Plasma NT-proBNP (pg/mL) values were averaged from Week 4 and Week 8 visits. N-terminal pro b-type natriuretic peptide (NTproBNP) are peptide (small proteins) that are either hormones or part of the peptide that contained the hormone at one time. They are continually produced in small quantities in the heart and released in larger quantities when the heart senses that it needs to work harder, as in heart failure.
次要结局
- Change From Baseline in High Sensitivity Troponin (Hs-Troponin)(Baseline, Week 4/Week 8)
- Number of Patients With Incidences of Symptomatic Hypotension(8 weeks of treatment)
- Number of Patients With Incidences of Hyperkalemia(8 weeks of treatment)
- Change From Baseline in Urinary cGMP(Baseline, Week 4 and Week 8)
- Change From Baseline in BNP to NTproBNP Ratio(baseline, Week 4 and Week 8)
- N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) Values and Change From Baseline at Week 8(Baseline, Week 8)
- Number of Patients With Incidences of Angioedema(8 weeks of treatment)
- Change From Baseline in Urinary cGMP to Urinary Creatinine Ratio(Baseline, Week 4 and Week 8)