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CompletedNCT04883528PARACOR-19Updated Jul 3, 2024Results posted

Protecting With ARNI Against Cardiac Consequences of Coronavirus Disease 2019

A Phase 1/2 interventional study of Sacubitril / Valsartan Oral Tablet [Entresto] and Placebo in Covid19, sponsored by Duke University. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-07-03.

Sponsored by Duke University · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
42
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Covid19

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Keywords

  • sacubitril/valsartan
03

In context

COVID-19

7,774 studies on the registry are indexed under COVID-19; 482 are open to participants now.

This study's enrollment of 42 is below the median of 100 across 4,175 interventional studies indexed under COVID-19.

Browse COVID-19 studies →

Lead sponsor

Duke University is the lead sponsor of 2,058 studies on the registry; 274 are open to participants now.

Of its 204 completed or terminated interventional studies of FDA-regulated products, 165 (81%) have results posted.

Browse Duke University studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
42 participants (actual)

Study arms

  • Experimental
    Sacubitril/valsartan

    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 comparator
    Placebo

    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

  • DrugSacubitril / Valsartan Oral Tablet [Entresto]

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

    Also known as: LCZ696

  • DrugPlacebo

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

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Baseline, Week 12

  2. 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.

    Time frame: Baseline, Week 12

Secondary outcomes

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

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

    Time frame: Baseline, Week 12

  2. 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.

    Time frame: Baseline, Week 12

  3. 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.

    Time frame: Baseline, Week 12

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

    Higher levels of NT-proBNP indicate increased heart failure.

    Time frame: Baseline, Week 12

  5. 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.

    Time frame: Baseline, Week 12

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

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

    Time frame: Baseline, Week 12

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

    Elevated levels of CITP indicate increased bone turnover.

    Time frame: Baseline, Week 12

  8. 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%.

    Time frame: Baseline, Week 12

  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

    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.

    Time frame: Baseline, Week 12

  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).

    Time frame: Baseline, Week 12

07

Results

Posted Jul 3, 2024

Participant flow

Participant flow — Overall Study
MilestoneSacubitril/ValsartanPlacebo
Started2022
Completed2022
Not completed00

Outcome measures

PrimaryChange 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.

Time frame:
Baseline, Week 12
Reported as:
Geometric mean · ng/mL
Change From Baseline in High-sensitivity Troponin T
ng/mLSacubitril/ValsartanPlacebo
Change From Baseline in High-sensitivity Troponin T1.12 (0.99 to 1.26)1.01 (0.87 to 1.17)
Statistical analysis
  • Sacubitril/Valsartan vs Placebo · Mixed Models Analysis · p = 0.29
PrimaryChange 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.

Time frame:
Baseline, Week 12
Reported as:
Geometric mean · ng/mL
Change From Baseline in Soluble ST2
ng/mLSacubitril/ValsartanPlacebo
Change From Baseline in Soluble ST20.95 (0.81 to 1.10)0.96 (0.80 to 1.15)
Statistical analysis
  • Sacubitril/Valsartan vs Placebo · Mixed Models Analysis · p = 0.88
SecondaryChange From Baseline in C-reactive Peptide (CRP)

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

Time frame:
Baseline, Week 12
Reported as:
Geometric mean · mg/dL
Change From Baseline in C-reactive Peptide (CRP)
mg/dLSacubitril/ValsartanPlacebo
Change From Baseline in C-reactive Peptide (CRP)0.94 (0.68 to 1.29)0.87 (0.55 to 1.36)
Statistical analysis
  • Sacubitril/Valsartan vs Placebo · Mixed Models Analysis · p = 0.76
SecondaryChange 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.

Time frame:
Baseline, Week 12
Reported as:
Geometric mean · mcg/L
Change From Baseline in P1NP (Procollagen Type I N-propeptide)
mcg/LSacubitril/ValsartanPlacebo
Change From Baseline in P1NP (Procollagen Type I N-propeptide)0.98 (0.91 to 1.05)0.99 (0.91 to 1.06)
Statistical analysis
  • Sacubitril/Valsartan vs Placebo · Mixed Models Analysis · p = 0.85
SecondaryChange 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.

Time frame:
Baseline, Week 12
Reported as:
Geometric mean · ng/mL
Change From Baseline in Galectin-3
ng/mLSacubitril/ValsartanPlacebo
Change From Baseline in Galectin-30.89 (0.77 to 1.02)0.91 (0.77 to 1.09)
Statistical analysis
  • Sacubitril/Valsartan vs Placebo · Mixed Models Analysis · p = 0.80
SecondaryChange From Baseline in NT-proBNP (N-terminal Pro B-type Natriuretic Peptide)

Higher levels of NT-proBNP indicate increased heart failure.

Time frame:
Baseline, Week 12
Reported as:
Geometric mean · pg/mL
Change From Baseline in NT-proBNP (N-terminal Pro B-type Natriuretic Peptide)
pg/mLSacubitril/ValsartanPlacebo
Change From Baseline in NT-proBNP (N-terminal Pro B-type Natriuretic Peptide)0.60 (0.42 to 0.85)1.11 (0.85 to 1.45)
Statistical analysis
  • Sacubitril/Valsartan vs Placebo · Mixed Models Analysis · p = 0.01
SecondaryChange 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.

Time frame:
Baseline, Week 12
Reported as:
Geometric mean · pg/mL
Change From Baseline in GDF-15 (Growth/Differentiation Factor-15)
pg/mLSacubitril/ValsartanPlacebo
Change From Baseline in GDF-15 (Growth/Differentiation Factor-15)1.14 (0.98 to 1.33)1.00 (0.85 to 1.17)
Statistical analysis
  • Sacubitril/Valsartan vs Placebo · Mixed Models Analysis · p = 0.23
SecondaryChange From Baseline in IL-6 (Interleukin-6)

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

Time frame:
Baseline, Week 12
Reported as:
Geometric mean · pg/mL
Change From Baseline in IL-6 (Interleukin-6)
pg/mLSacubitril/ValsartanPlacebo
Change From Baseline in IL-6 (Interleukin-6)1.10 (0.52 to 2.36)1.07 (0.59 to 1.93)
Statistical analysis
  • Sacubitril/Valsartan vs Placebo · Mixed Models Analysis · p = 0.95
SecondaryChange From Baseline in CITP (C-terminal Telopeptide of Collagen Type I)

Elevated levels of CITP indicate increased bone turnover.

Time frame:
Baseline, Week 12
Reported as:
Geometric mean · ng/mL
Change From Baseline in CITP (C-terminal Telopeptide of Collagen Type I)
ng/mLSacubitril/ValsartanPlacebo
Change From Baseline in CITP (C-terminal Telopeptide of Collagen Type I)0.77 (0.50 to 1.18)1.55 (0.98 to 2.46)
Statistical analysis
  • Sacubitril/Valsartan vs Placebo · Mixed Models Analysis · p = 0.03
SecondaryChange 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%.

Time frame:
Baseline, Week 12
Reported as:
Mean · percentage of blood
Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
percentage of bloodSacubitril/ValsartanPlacebo
Change From Baseline in Left Ventricular Ejection Fraction (LVEF)0.5 (-4.7 to 5.7)0.5 (-1.8 to 2.8)
SecondaryChange From Baseline in Focal Fibrosis by Delayed-enhancement on Cardiac MRI
Time frame:
Baseline, Week 12

No measurements were reported for this outcome.

SecondaryChange From Baseline in Focal Fibrosis by Percentage of Left Ventricular Myocardial Mass on Cardiac MRI
Time frame:
Baseline, Week 12

No measurements were reported for this outcome.

SecondaryChange 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.

Time frame:
Baseline, Week 12
Reported as:
Least squares mean · score on a scale
Change From Baseline in EuroQol-5 Dimensions (EQ-5D) Utility Score
score on a scaleSacubitril/ValsartanPlacebo
Change From Baseline in EuroQol-5 Dimensions (EQ-5D) Utility Score0.01 (-0.04 to 0.06)0.03 (0.00 to 0.05)
Statistical analysis
  • Sacubitril/Valsartan vs Placebo · Mixed Models Analysis · p = 0.64 · Least squares mean difference: -0.01 · 95% CI -0.07 to 0.04
SecondaryChange 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).

Time frame:
Baseline, Week 12
Reported as:
Least squares mean · score on a scale
Change From Baseline in EuroQOL-5 Dimensions (EQ-5D) Visual Analog Scale (VAS)
score on a scaleSacubitril/ValsartanPlacebo
Change From Baseline in EuroQOL-5 Dimensions (EQ-5D) Visual Analog Scale (VAS)-5.60 (-11.60 to 0.40)1.95 (-1.73 to 5.64)
Statistical analysis
  • Sacubitril/Valsartan vs Placebo · Mixed Models Analysis · p = 0.04 · Least squares mean difference: -7.55 · 95% CI -14.59 to 0.52

Adverse events

Collected over 12 weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Sacubitril/Valsartan0/20 (0%)0/20 (0%)0/20 (0%)
Placebo0/22 (0%)0/22 (0%)0/22 (0%)

Baseline characteristics

Age, Continuous
Age, Continuous(years)Sacubitril/ValsartanPlaceboTotal
Median65 (61 to 70)69 (65 to 71)67 (61 to 71)
Sex: Female, Male
Sex: Female, Male(Participants)Sacubitril/ValsartanPlaceboTotal
Female91120
Male111122
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Sacubitril/ValsartanPlaceboTotal
Hispanic or Latino011
Not Hispanic or Latino202141
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Sacubitril/ValsartanPlaceboTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American314
White172138
More than one race000
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(Participants)Sacubitril/ValsartanPlaceboTotal
United States202242
08

Study locations

1 site
  • Duke University Medical Center
    Durham, North Carolina 27710, United States
09

References and documents

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 documents

  • Protocol and statistical analysis plan · Feb 26, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Aug 2021 to primary completion in Jun 2023, 22 months.

Results were first posted in Jul 2024, 1 year after primary completion.

Of 99 non-industry phase 1/2 interventional studies under COVID-19, half reached primary completion within 9 months of starting (the median), counting those still running; a quarter within 3 and three quarters within 21. This study's 22 months is above that.

Counting every sponsor, half of 171 studies reached it within 9 months; a quarter within 3 and three quarters within 19.

How these figures are worked out, and which studies are left out of them.

Registered
May 6, 2021
First posted
May 12, 2021
StartActual
Aug 6, 2021
Primary completionActual
Jun 13, 2023
CompletionActual
Jun 13, 2023
Results first posted
Jul 3, 2024
Last update
Jul 3, 2024
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Jul 3, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04883528
Lead sponsor
Duke University
Collaborators
Novartis Pharmaceuticals
Responsible party
Sponsor
First posted
May 12, 2021
Start date
Aug 6, 2021
Primary completion
Jun 13, 2023
Completion
Jun 13, 2023
Results posted
Jul 3, 2024
Last update
Jul 3, 2024

Study contacts

Stephen J Greene, MD
principal investigator · Duke University
G. Michael Felker, MD, MHS
principal investigator · Duke University

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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