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| Name | Class |
|---|---|
| Novartis Pharmaceuticals | INDUSTRY |
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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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | Baseline, Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in C-reactive Peptide (CRP) | CRP is a pentameric protein synthesized by the liver; its level rises in response to inflammation. | Baseline, Week 12 |
| Change From Baseline in P1NP (Procollagen Type I N-propeptide) |
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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:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Stephen J Greene, MD | Duke University | Principal Investigator |
| G. Michael Felker, MD, MHS | Duke University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38733160 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 Sacubitril / Valsartan Oral Tablet [Entresto]: sacubitril/valsartan (LCZ696) tablet with minimum dose 24/26 mg, maximum dose 97/103 mg twice daily administered orally. |
| FG001 | 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. Placebo: sacubitril/valsartan matching placebo tablet with minimum dose 24/26 mg, maximum dose 97/103 mg twice daily administered orally. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 Sacubitril / Valsartan Oral Tablet [Entresto]: sacubitril/valsartan (LCZ696) tablet with minimum dose 24/26 mg, maximum dose 97/103 mg twice daily administered orally. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Geometric Mean | 95% Confidence Interval | ng/mL | Baseline, Week 12 |
|
12 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 Sacubitril / Valsartan Oral Tablet [Entresto]: sacubitril/valsartan (LCZ696) tablet with minimum dose 24/26 mg, maximum dose 97/103 mg twice daily administered orally. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Stephen J. Greene, MD | Duke University | 919-684-3854 | stephen.greene@duke.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 26, 2023 | May 23, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| C000717211 | sacubitril |
| D000068756 | Valsartan |
| C549068 | sacubitril and valsartan sodium hydrate drug combination |
| ID | Term |
|---|---|
| D013777 | Tetrazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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|
| Placebo | Drug | sacubitril/valsartan matching placebo tablet with minimum dose 24/26 mg, maximum dose 97/103 mg twice daily administered orally. |
|
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.
| 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. | 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. | 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. | 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. | Baseline, Week 12 |
| Change From Baseline in CITP (C-terminal Telopeptide of Collagen Type I) | Elevated levels of CITP indicate increased bone turnover. | 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%. | Baseline, Week 12 |
| Change From Baseline in Focal Fibrosis by Delayed-enhancement on Cardiac MRI | Baseline, Week 12 |
| Change From Baseline in Focal Fibrosis by Percentage of Left Ventricular Myocardial Mass on Cardiac MRI | 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. | 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). | Baseline, Week 12 |
| BG001 | 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. Placebo: sacubitril/valsartan matching placebo tablet with minimum dose 24/26 mg, maximum dose 97/103 mg twice daily administered orally. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 | 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. Placebo: sacubitril/valsartan matching placebo tablet with minimum dose 24/26 mg, maximum dose 97/103 mg twice daily administered orally. |
|
|
|
| Primary | 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. | Posted | Geometric Mean | 95% Confidence Interval | ng/mL | Baseline, Week 12 |
|
|
|
|
| Secondary | Change From Baseline in C-reactive Peptide (CRP) | CRP is a pentameric protein synthesized by the liver; its level rises in response to inflammation. | Posted | Geometric Mean | 95% Confidence Interval | mg/dL | Baseline, Week 12 |
|
|
|
|
| Secondary | 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. | Posted | Geometric Mean | 95% Confidence Interval | mcg/L | Baseline, Week 12 |
|
|
|
|
| Secondary | 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. | Posted | Geometric Mean | 95% Confidence Interval | ng/mL | Baseline, Week 12 |
|
|
|
|
| Secondary | Change From Baseline in NT-proBNP (N-terminal Pro B-type Natriuretic Peptide) | Higher levels of NT-proBNP indicate increased heart failure. | Posted | Geometric Mean | 95% Confidence Interval | pg/mL | Baseline, Week 12 |
|
|
|
|
| Secondary | 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. | Posted | Geometric Mean | 95% Confidence Interval | pg/mL | Baseline, Week 12 |
|
|
|
|
| Secondary | Change From Baseline in IL-6 (Interleukin-6) | IL-6 can be elevated with inflammation, infection, autoimmune disorders, cardiovascular diseases, and some cancers. | Posted | Geometric Mean | 95% Confidence Interval | pg/mL | Baseline, Week 12 |
|
|
|
|
| Secondary | Change From Baseline in CITP (C-terminal Telopeptide of Collagen Type I) | Elevated levels of CITP indicate increased bone turnover. | Posted | Geometric Mean | 95% Confidence Interval | ng/mL | Baseline, Week 12 |
|
|
|
|
| Secondary | 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%. | Participants who consented to this optional substudy. | Posted | Mean | 95% Confidence Interval | percentage of blood | Baseline, Week 12 |
|
|
|
| Secondary | Change From Baseline in Focal Fibrosis by Delayed-enhancement on Cardiac MRI | Data not collected. | Posted | Baseline, Week 12 |
|
|
| Secondary | Change From Baseline in Focal Fibrosis by Percentage of Left Ventricular Myocardial Mass on Cardiac MRI | Data not collected. | Posted | Baseline, Week 12 |
|
|
| Secondary | 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. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Baseline, Week 12 |
|
|
|
|
| Secondary | 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). | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Baseline, Week 12 |
|
|
|
|
| 0 |
| 20 |
| 0 |
| 20 |
| 0 |
| 20 |
| EG001 | 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. Placebo: sacubitril/valsartan matching placebo tablet with minimum dose 24/26 mg, maximum dose 97/103 mg twice daily administered orally. | 0 | 22 | 0 | 22 | 0 | 22 |
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| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D014633 |
| Valine |
| D000597 | Amino Acids, Branched-Chain |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000601 | Amino Acids, Essential |