PARACOR-19: Protecting With ARNI Against Cardiac Consequences of Coronavirus Disease 2019
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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 |
Drug: Sacubitril / Valsartan Oral Tablet [Entresto]
sacubitril/valsartan (LCZ696) tablet with minimum dose 24/26 mg, maximum dose 97/103 mg twice daily administered orally.
Other Names:
|
| Placebo Comparator: 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, adminstered twice daily orally. |
Drug: Placebo
sacubitril/valsartan matching placebo tablet with minimum dose 24/26 mg, maximum dose 97/103 mg twice daily administered orally.
|
Outcome Measures
Primary Outcome Measures
- Change from baseline in high-sensitivity troponin T [Baseline, Week 12]
- Change from baseline in soluble ST2 [Baseline, Week 12]
Secondary Outcome Measures
- 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]
Eligibility Criteria
Criteria
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
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Systolic blood pressure ≥100 mmHg at screening
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≥18 years of age
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Successful collection of baseline serum biomarkers
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Successful completion of baseline EQ-5D questionnaire
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Successful completion of baseline CMR study (CMR sub-study only)
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High-sensitivity troponin T at or above the level of detection on screening labs
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Presence of ≥1 of the following:
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Age ≥60
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History of atherosclerotic cardiovascular disease (ASCVD), including myocardial infarction, coronary artery disease, ischemic stroke/transient ischemic attack, or peripheral artery disease
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Diabetes mellitus (Type 1 or Type 2)
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Body mass index ≥35 kg/m2
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eGFR 30-60 ml/min/1.73m2
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History of atrial fibrillation/flutter
Exclusion Criteria:
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Fever within the past 96 hours of >100.3 degrees Fahrenheit
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Actively receiving therapy with an angiotensin-converting enzyme inhibitor (ACEI), angiotensin II receptor blocker (ARB), aliskiren, or sacubitril/valsartan
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Last known left ventricular ejection fraction of ≤40%
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eGFR <30 ml/min/1.73m2 on screening labs, including patients on dialysis therapy
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Serum potassium >5.0 mEq/L on screening labs
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Prior intolerance, allergy or angioedema to ACEI, ARB, or sacubitril/valsartan
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Pregnant or breast-feeding
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In women of childbearing age, unwillingness to use birth control for the duration of the study
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History of heart transplant or durable left ventricular assist device
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Currently implanted permanent pacemaker, defibrillator, or other device that would preclude CMR testing (CMR sub-study only)
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Currently participating in another trial of an investigational medication or device for COVID-19.
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Any other condition that in the judgment of the investigator would jeopardize the patient's compliance with the study protocol
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Duke University Medical Center | Durham | North Carolina | United States | 27710 |
Sponsors and Collaborators
- Duke University
- Novartis Pharmaceuticals
Investigators
- Principal Investigator: Stephen J Greene, MD, Duke University
- Principal Investigator: G. Michael Felker, MD, MHS, Duke University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Pro00108314