Clinical trial NCT04883528: Protecting With ARNI Against Cardiac Consequences of Coronavirus Disease 2019
Official title: Protecting With ARNI Against Cardiac Consequences of Coronavirus Disease 2019
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Covid19
Keywords: sacubitril/valsartan
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
First posted: 2021-05-12
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change From Baseline in High-sensitivity Troponin T
timeFrame: Baseline, Week 12
measure: Change From Baseline in Soluble ST2
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Change From Baseline in C-reactive Peptide (CRP)
timeFrame: Baseline, Week 12
measure: Change From Baseline in P1NP (Procollagen Type I N-propeptide)
timeFrame: Baseline, Week 12
measure: Change From Baseline in Galectin-3
timeFrame: Baseline, Week 12
measure: Change From Baseline in NT-proBNP (N-terminal Pro B-type Natriuretic Peptide)
timeFrame: Baseline, Week 12
measure: Change From Baseline in GDF-15 (Growth/Differentiation Factor-15)
timeFrame: Baseline, Week 12
measure: Change From Baseline in IL-6 (Interleukin-6)
timeFrame: Baseline, Week 12
measure: Change From Baseline in CITP (C-terminal Telopeptide of Collagen Type I)
timeFrame: Baseline, Week 12
measure: Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
timeFrame: Baseline, Week 12
measure: Change From Baseline in Focal Fibrosis by Delayed-enhancement on Cardiac MRI
timeFrame: Baseline, Week 12
measure: Change From Baseline in Focal Fibrosis by Percentage of Left Ventricular Myocardial Mass on Cardiac MRI
timeFrame: Baseline, Week 12
measure: Change From Baseline in EuroQol-5 Dimensions (EQ-5D) Utility Score
timeFrame: Baseline, Week 12
measure: Change From Baseline in EuroQOL-5 Dimensions (EQ-5D) Visual Analog Scale (VAS)
timeFrame: Baseline, Week 12
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Stephen J Greene, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: G. Michael Felker, MD, MHS
role: PRINCIPAL_INVESTIGATOR
References: