Protecting With ARNI Against Cardiac Consequences of Coronavirus Disease 2019

Study Overview
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Brief Summary
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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.

Official Title
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Protecting With ARNI Against Cardiac Consequences of Coronavirus Disease 2019

Conditions
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Covid19

Intervention / Treatment
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* Drug: Sacubitril / Valsartan Oral Tablet [Entresto]
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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: Age ≥60 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 Exclusion Criteria: 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-19. Any other condition that in the judgment of the investigator would jeopardize the patient's compliance with the study protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sacubitril/valsartan<br>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 | Drug: Sacubitril / Valsartan Oral Tablet [Entresto]<br>* sacubitril/valsartan (LCZ696) tablet with minimum dose 24/26 mg, maximum dose 97/103 mg twice daily administered orally.<br>* Other names: LCZ696;|
| Placebo Comparator: Placebo<br>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, adminstered twice daily orally. | Drug: Placebo<br>* sacubitril/valsartan matching placebo tablet with minimum dose 24/26 mg, maximum dose 97/103 mg twice daily administered orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in high-sensitivity troponin T |  | Baseline, Week 12 | 
| Change from baseline in soluble ST2 |  | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in C-reactive peptide |  | Baseline, Week 12 | 
| Change from baseline in PINP |  | Baseline, Week 12 | 
| Change from baseline in Galectin-3 |  | Baseline, Week 12 | 
| Change from baseline in NT-proBNP |  | Baseline, Week 12 | 
| Change from baseline in GDF-15 |  | Baseline, Week 12 | 
| Change from baseline in interleukin-6 |  | Baseline, Week 12 | 
| Change from baseline in cardiac MRI measures |  | 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 utility score |  | Baseline, Week 12 | 
| Change from baseline in EuroQOL-5 dimensions visual analog scale |  | Baseline, Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sacubitril/valsartan