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

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.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Drug: Sacubitril / Valsartan Oral Tablet [Entresto]; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Stephen Greene, MD; Phone Number: 919 684 8111; Email: stephen.greene@duke.edu

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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: LCZ696
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Novartis Pharmaceuticals
• Investigators: Principal Investigator: Stephen J Greene, MD, Duke University; Principal Investigator: G. Michael Felker, MD, MHS, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): August 6, 2021
• Primary Completion (Actual): June 13, 2023
• Study Completion (Actual): June 13, 2023

Study Registration Dates

• First Submitted: May 6, 2021
• First Submitted That Met QC Criteria: May 11, 2021
• First Posted (Actual): May 12, 2021

Study Record Updates

• Last Update Posted (Actual): September 6, 2023
• Last Update Submitted That Met QC Criteria: September 1, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: sacubitril/valsartan
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Valsartan; Sacubitril and valsartan sodium hydrate drug combination
• Other Study ID Numbers: Pro00108314

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No