Protecting With ARNI Against Cardiac Consequences of Coronavirus Disease 2019
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Change From Baseline in High-sensitivity Troponin T
研究概览
简要总结
The purpose of this study is to determine the effect of sacubitril/valsartan versus placebo on markers of cardiac injury, structure, and function among patients who recovered from acute COVID-19 infection.
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
- 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
- •Patient with a history of laboratory proven-diagnosis of COVID-19 who is 4-16 weeks from their last positive COVID-19 test
- •Systolic blood pressure ≥100 mmHg at screening
- •≥18 years of age
- •Successful collection of baseline serum biomarkers
- •Successful completion of baseline EQ-5D questionnaire
- •Successful completion of baseline CMR study (CMR sub-study only)
- •High-sensitivity troponin T at or above the level of detection on screening labs
- •Presence of ≥1 of the following:
- •History of atherosclerotic cardiovascular disease (ASCVD), including myocardial infarction, coronary artery disease, ischemic stroke/transient ischemic attack, or peripheral artery disease
- •Diabetes mellitus (Type 1 or Type 2)
- •Body mass index ≥35 kg/m2
- •eGFR 30-60 ml/min/1.73m2
- •History of atrial fibrillation/flutter
排除标准
- •Fever within the past 96 hours of >100.3 degrees Fahrenheit
- •Actively receiving therapy with an angiotensin-converting enzyme inhibitor (ACEI), angiotensin II receptor blocker (ARB), aliskiren, or sacubitril/valsartan
- •Last known left ventricular ejection fraction of ≤40%
- •eGFR <30 ml/min/1.73m2 on screening labs, including patients on dialysis therapy
- •Serum potassium >5.0 mEq/L on screening labs
- •Prior intolerance, allergy or angioedema to ACEI, ARB, or sacubitril/valsartan
- •Pregnant or breast-feeding
- •In women of childbearing age, unwillingness to use birth control for the duration of the study
- •History of heart transplant or durable left ventricular assist device
- •Currently implanted permanent pacemaker, defibrillator, or other device that would preclude CMR testing (CMR sub-study only)
- •Currently participating in another trial of an investigational medication or device for COVID-
- •Any other condition that in the judgment of the investigator would jeopardize the patient's compliance with the study protocol
研究组 & 干预措施
Sacubitril/valsartan
Initial dose for patients randomized to sacubitril/valsartan (LCZ696) will be determined by the blood pressure at the time of randomization. Study treatment will be titrated to the next highest dose (dose level 2 or 3) based on blood pressure at the time of visit 2/titration visit. Dose adjustments are only allowed if indicated per protocol defined criteria and per investigator judgement of safety and tolerability.
Sacubitril/valsartan (LCZ696) tablet with minimum dose 24/26 mg, maximum dose 97/103 mg twice daily administered orally.
Other Name: LCZ696
干预措施: Sacubitril / Valsartan Oral Tablet [Entresto] (Drug)
Placebo
Initial dose for patients randomized to sacubitril/valsartan matching placebo will be determined by the blood pressure at the time of randomization. Study treatment will be titrated to the next highest dose (dose level 2 or 3) based on blood pressure at the time of visit 2/titration visit. Dose adjustments are only allowed if indicated per protocol defined criteria and per investigator judgement of safety and tolerability.
Sacubitril/valsartan matching placebo with minimum dose matching the 24/26 mg dose, maximum dose matching the 97/103 mg dose, administered twice daily orally.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in High-sensitivity Troponin T
时间窗: Baseline, Week 12
An elevated level of troponin T on the high-sensitivity cardiac troponin test indicates heart muscle damage or a heart attack.
Change From Baseline in Soluble ST2
时间窗: Baseline, Week 12
ST2 is a decoy receptor that inhibits beneficial cardioprotective effects of IL-33; such inhibition results in cardiac hypertrophy, myocardial fibrosis, and ventricular dysfunction. Measurement of soluble ST2 has utility for assessing heart failure severity and prognosis.
次要结局
- Change From Baseline in C-reactive Peptide (CRP)(Baseline, Week 12)
- Change From Baseline in P1NP (Procollagen Type I N-propeptide)(Baseline, Week 12)
- Change From Baseline in Galectin-3(Baseline, Week 12)
- Change From Baseline in NT-proBNP (N-terminal Pro B-type Natriuretic Peptide)(Baseline, Week 12)
- Change From Baseline in GDF-15 (Growth/Differentiation Factor-15)(Baseline, Week 12)
- Change From Baseline in CITP (C-terminal Telopeptide of Collagen Type I)(Baseline, Week 12)
- Change From Baseline in Left Ventricular Ejection Fraction (LVEF)(Baseline, Week 12)
- Change From Baseline in IL-6 (Interleukin-6)(Baseline, Week 12)
- Change From Baseline in Focal Fibrosis by Delayed-enhancement on Cardiac MRI(Baseline, Week 12)
- Change From Baseline in Focal Fibrosis by Percentage of Left Ventricular Myocardial Mass on Cardiac MRI(Baseline, Week 12)
- Change From Baseline in EuroQol-5 Dimensions (EQ-5D) Utility Score(Baseline, Week 12)
- Change From Baseline in EuroQOL-5 Dimensions (EQ-5D) Visual Analog Scale (VAS)(Baseline, Week 12)