Protecting With ARNI Against Cardiac Consequences of Coronavirus Disease 2019

NCT04883528 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: Pro00108314
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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

Keywords

sacubitril/valsartan

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in High-sensitivity Troponin T

  An elevated level of troponin T on the high-sensitivity cardiac troponin test indicates heart muscle damage or a heart attack.

  Baseline, Week 12

• Change From Baseline in Soluble ST2

  ST2 is a decoy receptor that inhibits beneficial cardioprotective effects of IL-33; such inhibition results in cardiac hypertrophy, myocardial fibrosis, and ventricular dysfunction. Measurement of soluble ST2 has utility for assessing heart failure severity and prognosis.

  Baseline, Week 12

Secondary Outcomes (12)

• Change From Baseline in C-reactive Peptide (CRP)

  Baseline, Week 12

• Change From Baseline in P1NP (Procollagen Type I N-propeptide)

  Baseline, Week 12

• Change From Baseline in Galectin-3

  Baseline, Week 12

• Change From Baseline in NT-proBNP (N-terminal Pro B-type Natriuretic Peptide)

  Baseline, Week 12

• Change From Baseline in GDF-15 (Growth/Differentiation Factor-15)

  Baseline, Week 12

Study Arms (2)

Sacubitril/valsartan

EXPERIMENTAL

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]

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Sacubitril / Valsartan Oral Tablet [Entresto] DRUG

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

Also known as: LCZ696

Sacubitril/valsartan

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Duke University: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• 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.

  PMID: 38733160 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

sacubitril; Valsartan; sacubitril and valsartan sodium hydrate drug combination

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Results Point of Contact

• Title: Stephen J. Greene, MD
• Organization: Duke University

stephen.greene@duke.edu

919-684-3854

Study Officials

• Stephen J Greene, MD

  Duke University

  PRINCIPAL INVESTIGATOR

• G. Michael Felker, MD, MHS

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2021
• First Posted: May 12, 2021
• Study Start: August 6, 2021
• Primary Completion: June 13, 2023
• Study Completion: June 13, 2023
• Last Updated: July 3, 2024
• Results First Posted: July 3, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)