Protecting With ARNI Against Cardiac Consequences of Coronavirus Disease 2019 (PARACOR-19)

Duke University

Status and phase: Completed; Phase 2; Phase 1

Conditions: Covid19

Treatments: Drug: Sacubitril / Valsartan Oral Tablet [Entresto]; Drug: Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04883528

Pro00108314

Details and patient eligibility

About

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.

Enrollment: 42 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patient with a history of laboratory proven-diagnosis of COVID-19 who is 4-16 weeks from their last positive COVID-19 test

2. Systolic blood pressure ≥100 mmHg at screening

3. ≥18 years of age

4. Successful collection of baseline serum biomarkers

5. Successful completion of baseline EQ-5D questionnaire

6. Successful completion of baseline CMR study (CMR sub-study only)

7. High-sensitivity troponin T at or above the level of detection on screening labs

8. Presence of ≥1 of the following:

   1. Age ≥60
   2. History of atherosclerotic cardiovascular disease (ASCVD), including myocardial infarction, coronary artery disease, ischemic stroke/transient ischemic attack, or peripheral artery disease
   3. Diabetes mellitus (Type 1 or Type 2)
   4. Body mass index ≥35 kg/m2
   5. eGFR 30-60 ml/min/1.73m2
   6. History of atrial fibrillation/flutter

Exclusion criteria

1. Fever within the past 96 hours of >100.3 degrees Fahrenheit
2. Actively receiving therapy with an angiotensin-converting enzyme inhibitor (ACEI), angiotensin II receptor blocker (ARB), aliskiren, or sacubitril/valsartan
3. Last known left ventricular ejection fraction of ≤40%
4. eGFR <30 ml/min/1.73m2 on screening labs, including patients on dialysis therapy
5. Serum potassium >5.0 mEq/L on screening labs
6. Prior intolerance, allergy or angioedema to ACEI, ARB, or sacubitril/valsartan
7. Pregnant or breast-feeding
8. In women of childbearing age, unwillingness to use birth control for the duration of the study
9. History of heart transplant or durable left ventricular assist device
10. Currently implanted permanent pacemaker, defibrillator, or other device that would preclude CMR testing (CMR sub-study only)
11. Currently participating in another trial of an investigational medication or device for COVID-19.
12. Any other condition that in the judgment of the investigator would jeopardize the patient's compliance with the study protocol

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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42 participants in 2 patient groups, including a placebo group

Sacubitril/valsartan

Experimental group

Description:

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

Treatment:

Drug: Sacubitril / Valsartan Oral Tablet [Entresto]

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo