Covid19Phase 1/2PARACOR-19NCT04883528
Protecting With ARNI Against Cardiac Consequences of Coronavirus Disease 2019
A Phase 1/2 study testing Sacubitril / Valsartan Oral Tablet [Entresto] in people with Covid19, run by Duke University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19
- What is being tested?
- Sacubitril / Valsartan Oral Tablet [Entresto]
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Aug 2021to 13 Jun 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
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
- Being tested
- Sacubitril / Valsartan Oral Tablet [Entresto], Placebo
- Keywords
- sacubitril/valsartan
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sacubitril / Valsartan Oral Tablet [Entresto]Drug
Also called LCZ696
sacubitril/valsartan (LCZ696) tablet with minimum dose 24/26 mg, maximum dose 97/103 mg twice daily administered orally.
PlaceboDrug
sacubitril/valsartan matching placebo tablet with minimum dose 24/26 mg, maximum dose 97/103 mg twice daily administered orally.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline, Week 12
Secondary outcomes (12)
Change From Baseline in C-reactive Peptide (CRP)
CRP is a pentameric protein synthesized by the liver; its level rises in response to inflammation.
Measured: Baseline, Week 12
Change From Baseline in P1NP (Procollagen Type I N-propeptide)
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.
Measured: Baseline, Week 12
Change From Baseline in Galectin-3
Galectin-3 may be used as a diagnostic or prognostic biomarker for certain types of heart disease, kidney disease and cancer.
Measured: Baseline, Week 12
Change From Baseline in NT-proBNP (N-terminal Pro B-type Natriuretic Peptide)
Higher levels of NT-proBNP indicate increased heart failure.
Measured: Baseline, Week 12
Change From Baseline in GDF-15 (Growth/Differentiation Factor-15)
Highly elevated GDF-15 levels are mostly linked to pathological conditions including inflammation, myocardial ischemia, and notably cancer.
Measured: Baseline, Week 12
Change From Baseline in IL-6 (Interleukin-6)
IL-6 can be elevated with inflammation, infection, autoimmune disorders, cardiovascular diseases, and some cancers.
Measured: Baseline, Week 12
Change From Baseline in CITP (C-terminal Telopeptide of Collagen Type I)
Elevated levels of CITP indicate increased bone turnover.
Measured: Baseline, Week 12
Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
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%.
Measured: Baseline, Week 12
Change From Baseline in Focal Fibrosis by Delayed-enhancement on Cardiac MRI
Measured: Baseline, Week 12
Change From Baseline in Focal Fibrosis by Percentage of Left Ventricular Myocardial Mass on Cardiac MRI
Measured: Baseline, Week 12
Change From Baseline in EuroQol-5 Dimensions (EQ-5D) Utility Score
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.
Measured: Baseline, Week 12
Change From Baseline in EuroQOL-5 Dimensions (EQ-5D) Visual Analog Scale (VAS)
The EQ-5D VAS is a scale from 0 (worst imaginable health state) to 100 (best imaginable health state).
Measured: Baseline, Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2021
- Study start6 Aug 2021
- Primary completion13 Jun 2023
- Study completion13 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Stephen J Greene, MD, Principal investigator, Duke UniversityG. Michael Felker, MD, MHS, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04883528
- Sponsor's protocol ID
- Pro00108314
- Acronym
- PARACOR-19
- Status last verified
- Jun 2024
- First submitted
- 6 May 2021
- Last updated
- 3 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 38733160
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Protecting With ARNI Against Cardiac Consequences of Coronavirus Disease 2019
- ClinicalTrials.gov ID
- NCT04883528
- Acronym / sponsor ID
- PARACOR-19 / Pro00108314
- Conditions
- Covid19
- Keywords
- sacubitril/valsartan
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- 6 Aug 2021 (actual)
- Primary completion
- 13 Jun 2023 (actual)
- Study completion
- 13 Jun 2023 (actual)
- First posted
- 12 May 2021 (actual)
- Results
- Posted 3 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sacubitril/valsartan | Experimental | Drug: Sacubitril / Valsartan Oral Tablet [Entresto]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 |
| Placebo | Placebo comparator | Drug: PlaceboInitial 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sacubitril / Valsartan Oral Tablet [Entresto]Also: LCZ696sacubitril/valsartan (LCZ696) tablet with minimum dose 24/26 mg, maximum dose 97/103 mg twice daily administered orally. | Drug | Sacubitril/valsartan |
| Placebosacubitril/valsartan matching placebo tablet with minimum dose 24/26 mg, maximum dose 97/103 mg twice daily administered orally. | Drug | Placebo |
Primary outcome
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.
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.
12 secondary outcomes
Change From Baseline in C-reactive Peptide (CRP)
Time frame: Baseline, Week 12
Change From Baseline in P1NP (Procollagen Type I N-propeptide)
Time frame: Baseline, Week 12
Change From Baseline in Galectin-3
Time frame: Baseline, Week 12
Change From Baseline in NT-proBNP (N-terminal Pro B-type Natriuretic Peptide)
Time frame: Baseline, Week 12
Change From Baseline in GDF-15 (Growth/Differentiation Factor-15)
Time frame: Baseline, Week 12
Change From Baseline in IL-6 (Interleukin-6)
Time frame: Baseline, Week 12
Change From Baseline in CITP (C-terminal Telopeptide of Collagen Type I)
Time frame: Baseline, Week 12
Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
Time frame: Baseline, Week 12
Change From Baseline in Focal Fibrosis by Delayed-enhancement on Cardiac MRI
Time frame: Baseline, Week 12
Change From Baseline in Focal Fibrosis by Percentage of Left Ventricular Myocardial Mass on Cardiac MRI
Time frame: Baseline, Week 12
Change From Baseline in EuroQol-5 Dimensions (EQ-5D) Utility Score
Time frame: Baseline, Week 12
Change From Baseline in EuroQOL-5 Dimensions (EQ-5D) Visual Analog Scale (VAS)
Time frame: Baseline, Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38733160Greene 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephen J Greene, MD principal investigator
Duke University
G. Michael Felker, MD, MHS principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Sacubitril / Valsartan Oral Tablet [Entresto] in people with Covid19, run by Duke University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in High-sensitivity Troponin T (time frame: Baseline, Week 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04883528, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2024.