Protecting With ARNI Against Cardiac Consequences of Coronavirus Disease 2019

NCT ID: NCT04883528

Last Updated: 2024-07-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-06
• Study Completion Date: 2023-06-13

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.

Conditions

Covid19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

Sacubitril / Valsartan Oral Tablet [Entresto]

Intervention Type: DRUG

sacubitril/valsartan (LCZ696) tablet with minimum dose 24/26 mg, maximum dose 97/103 mg twice daily administered orally.

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

sacubitril/valsartan matching placebo tablet with minimum dose 24/26 mg, maximum dose 97/103 mg twice daily administered orally.

Interventions

Sacubitril / Valsartan Oral Tablet [Entresto]

sacubitril/valsartan (LCZ696) tablet with minimum dose 24/26 mg, maximum dose 97/103 mg twice daily administered orally.

Intervention Type: DRUG

Placebo

sacubitril/valsartan matching placebo tablet with minimum dose 24/26 mg, maximum dose 97/103 mg twice daily administered orally.

Intervention Type: DRUG

Other Intervention Names

LCZ696

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephen J Greene, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

G. Michael Felker, MD, MHS

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

Duke University Medical Center

Durham, North Carolina, United States

Countries

United States

References

Greene SJ, Chambers R, Lerman JB, Harrington J, deFilippi CR, Wendell DC, Kim HW, Green CL, Butler J, Felker GM. Sacubitril/valsartan and cardiovascular biomarkers among patients with recent COVID-19 infection: The PARACOR-19 randomized clinical trial. Eur J Heart Fail. 2024 Jun;26(6):1393-1398. doi: 10.1002/ejhf.3199. Epub 2024 May 11.

Reference Type: DERIVED

PMID: 38733160 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Pro00108314

Identifier Type: -

Identifier Source: org_study_id