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

Primary Purpose

Covid19

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Sacubitril / Valsartan Oral Tablet [Entresto]

Placebo

About this trial

This is an interventional treatment trial for Covid19 focused on measuring sacubitril/valsartan

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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:
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:

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

Sites / Locations

Duke University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Sacubitril/valsartan

Placebo

Arm Description

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

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.

Outcomes

Primary Outcome Measures

Change from baseline in high-sensitivity troponin T

Change from baseline in soluble ST2

Secondary Outcome Measures

Change from baseline in C-reactive peptide

Change from baseline in PINP

Change from baseline in Galectin-3

Change from baseline in NT-proBNP

Change from baseline in GDF-15

Change from baseline in interleukin-6

Change from baseline in cardiac MRI measures

Change from baseline in focal fibrosis by delayed-enhancement on cardiac MRI

Change from baseline in focal fibrosis by percentage of left ventricular myocardial mass on cardiac MRI

Change from baseline in EuroQOL-5 dimensions utility score

Change from baseline in EuroQOL-5 dimensions visual analog scale

Full Information

NCT ID

NCT04883528

First Posted

May 6, 2021

Last Updated

September 1, 2023

Sponsor

Duke University

Collaborators

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT04883528

Brief Title

Protecting With ARNI Against Cardiac Consequences of Coronavirus Disease 2019

Acronym

PARACOR-19

Official Title

Protecting With ARNI Against Cardiac Consequences of Coronavirus Disease 2019

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Completed

Study Start Date

August 6, 2021 (Actual)

Primary Completion Date

June 13, 2023 (Actual)

Study Completion Date

June 13, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Duke University

Collaborators

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Covid19

Keywords

sacubitril/valsartan

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

42 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sacubitril/valsartan

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Sacubitril / Valsartan Oral Tablet [Entresto]

Other Intervention Name(s)

LCZ696

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

Change from baseline in high-sensitivity troponin T

Time Frame

Baseline, Week 12

Title

Change from baseline in soluble ST2

Time Frame

Baseline, Week 12

Secondary Outcome Measure Information:

Title

Change from baseline in C-reactive peptide

Time Frame

Baseline, Week 12

Title

Change from baseline in PINP

Time Frame

Baseline, Week 12

Title

Change from baseline in Galectin-3

Time Frame

Baseline, Week 12

Title

Change from baseline in NT-proBNP

Time Frame

Baseline, Week 12

Title

Change from baseline in GDF-15

Time Frame

Baseline, Week 12

Title

Change from baseline in interleukin-6

Time Frame

Baseline, Week 12

Title

Change from baseline in cardiac MRI measures

Time Frame

Baseline, Week 12

Title

Change from baseline in focal fibrosis by delayed-enhancement on cardiac MRI

Time Frame

Baseline, Week 12

Title

Change from baseline in focal fibrosis by percentage of left ventricular myocardial mass on cardiac MRI

Time Frame

Baseline, Week 12

Title

Change from baseline in EuroQOL-5 dimensions utility score

Time Frame

Baseline, Week 12

Title

Change from baseline in EuroQOL-5 dimensions visual analog scale

Time Frame

Baseline, Week 12

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Stephen J Greene, MD

Organizational Affiliation

Duke University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

G. Michael Felker, MD, MHS

Organizational Affiliation

Duke University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Duke University Medical Center

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27710

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Protecting With ARNI Against Cardiac Consequences of Coronavirus Disease 2019

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