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Completed

NCT Number: NCT04883528

Protecting With ARNI Against Cardiac Consequences of Coronavirus Disease 2019

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.

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Key information

Conditions

Covid19 COVID-19 Coronaviridae Infections Coronavirus Infections Infections Lung Diseases Nidovirales Infections Pneumonia Pneumonia, Viral RNA Virus Infections Respiratory Tract Diseases Respiratory Tract Infections Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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
  • 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

Exclusion criteria

  • 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

Treatment and study plan

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.

Other names: LCZ696

Placebo

Drug

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

Primary outcomes

  1. Change From Baseline in High-sensitivity Troponin T

    Time frame: Baseline, Week 12

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

  2. Change From Baseline in Soluble ST2

    Time frame: Baseline, Week 12

    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.

Secondary outcomes

  1. Change From Baseline in C-reactive Peptide (CRP)

    Time frame: Baseline, Week 12

    CRP is a pentameric protein synthesized by the liver; its level rises in response to inflammation.

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

    Time frame: Baseline, Week 12

    Serum P1NP is designated as the reference marker of bone formation in osteoporosis. Elevated markers are associated with increased bone turnover, which increases the deterioration of bone quality and the risk of fragility fracture.

  3. Change From Baseline in Galectin-3

    Time frame: Baseline, Week 12

    Galectin-3 may be used as a diagnostic or prognostic biomarker for certain types of heart disease, kidney disease and cancer.

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

    Time frame: Baseline, Week 12

    Higher levels of NT-proBNP indicate increased heart failure.

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

    Time frame: Baseline, Week 12

    Highly elevated GDF-15 levels are mostly linked to pathological conditions including inflammation, myocardial ischemia, and notably cancer.

  6. Change From Baseline in IL-6 (Interleukin-6)

    Time frame: Baseline, Week 12

    IL-6 can be elevated with inflammation, infection, autoimmune disorders, cardiovascular diseases, and some cancers.

  7. Change From Baseline in CITP (C-terminal Telopeptide of Collagen Type I)

    Time frame: Baseline, Week 12

    Elevated levels of CITP indicate increased bone turnover.

  8. Change From Baseline in Left Ventricular Ejection Fraction (LVEF)

    Time frame: Baseline, Week 12

    LVEF is the amount of blood pumped out of the heart's left ventricle each time it contracts, represented as a percentage of the blood in the left ventricle that gets pumped out to the body. Normal = LVEF 50% to 70% (midpoint 60%) Mild dysfunction = LVEF 40% to 49% (midpoint 45%) Moderate dysfunction = LVEF 30% to 39% (midpoint 35%) Severe dysfunction = LVEF less than 30%.

  9. Change From Baseline in Focal Fibrosis by Delayed-enhancement on Cardiac MRI

    Time frame: Baseline, Week 12

  10. Change From Baseline in Focal Fibrosis by Percentage of Left Ventricular Myocardial Mass on Cardiac MRI

    Time frame: Baseline, Week 12

  11. Change From Baseline in EuroQol-5 Dimensions (EQ-5D) Utility Score

    Time frame: Baseline, Week 12

    The EQ-5D utility score is a value that represents a person's health state based on a set of weights that reflect their preferences. The score is anchored at 0, which represents a state as bad as death, and 1, which represents full health. Negative values can be assigned to health states that are considered worse than death.

  12. Change From Baseline in EuroQOL-5 Dimensions (EQ-5D) Visual Analog Scale (VAS)

    Time frame: Baseline, Week 12

    The EQ-5D VAS is a scale from 0 (worst imaginable health state) to 100 (best imaginable health state).

Sponsors and collaborators

Lead sponsor

Duke University

Other

Collaborators

  • Novartis Pharmaceuticals

Registry information

Acronym: PARACOR-19

Important dates

Study start
2021
Primary completion
2023
Study completion
2023
First posted
May 12, 2021
Registry last updated
Jul 3, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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