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| ID | Type | Description | Link |
|---|---|---|---|
| INV-017069 | Other Grant/Funding Number | Bill and Melinda Gates Foundation |
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| Name | Class |
|---|---|
| Bill and Melinda Gates Foundation | OTHER |
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This is a multi-center, double-blinded study of COVID-19 infected patients requiring inpatient hospital admission randomized 1:1 to daily Losartan or placebo for 7 days or hospital discharge.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Losartan | Experimental | Participants in this arm will receive the study drug, Losartan. |
|
| Placebo | Placebo Comparator | Participants in this arm will receive a placebo treatment. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Losartan | Drug | Losartan; 50 mg daily; oral administration |
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| Measure | Description | Time Frame |
|---|---|---|
| Difference in Estimated (PEEP Adjusted) P/F Ratio at 7 Days | Outcome calculated from the partial pressure of oxygen or peripheral saturation of oxygen by pulse oximetry divided by the fraction of inspired oxygen (PaO2 or SaO2 : FiO2 ratio). PaO2 is preferentially used if available. A correction is applied for endotracheal intubation and/or positive end-expiratory pressure. Patients discharged prior to day 7 will have a home pulse oximeter send home for measurement of the day 7 value, and will be adjusted for home O2 use, if applicable. Patients who died will be applied a penalty with a P/F ratio of 0. | 7 days |
| Measure | Description | Time Frame |
|---|---|---|
| Daily Hypotensive Episodes | Outcome reported as the mean number of daily hypotensive episodes (MAP < 65 mmHg) prompting intervention (indicated by a fluid bolus >=500 mL) per participant in each arm. | 10 days |
| Proportion of Participants Requiring Vasopressors for Hypotension |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Randomization > 48 hours of admission order or positive test result, whichever is later
Currently taking an angiotensin converting enzyme inhibitor (ACEi) or Angiotensin receptor blocker (ARB)
Prior reaction or intolerance to an ARB or ACE inhibitor, including but not limited to angioedema
Pregnant or breastfeeding
Lack of negative urine or serum pregnancy test
Not currently taking a protocol allowed version of contraception: intrauterine device, Depo-formulation of hormonal contraception (e.g. medroxyprogesterone acetate / Depo-Provera), subcutaneous contraceptive (e.g. Nexplanon), daily oral contraceptives with verbalized commitment to taking daily throughout the study period; use of condoms or agree to abstain from sexual intercourse during the study. All women of child bearing age enrolled in this fashion will be informed of the teratogenic risks. If enrolled under LAR, they will be informed of the risks after regaining capacity.
Patient reported history or electronic medical record history of kidney disease, defined as:
Severe dehydration at the time of enrollment in the opinion of the investigator or bedside clinician
Most recent mean arterial blood pressure prior to enrollment <65 mmHg
Patient reported history or electronic medical record history of severe liver disease, defined as:
Potassium >5.0 within 24 hours prior to randomization unless a repeat value was <=5.0
Treatment with aliskiren
Inability to obtain informed consent from participant or legally authorized representative
Enrollment in another blinded randomized clinical trial for COVID
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| Name | Affiliation | Role |
|---|---|---|
| Christopher Tignanelli, MD | University of Minnesota | Principal Investigator |
| Michael Puskarich, MD, MS | University of Minnesota | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Florida Health Gainesville | Gainesville | Florida | 32611 | United States | ||
| University of Florida Health Jacksonville |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35294537 | Derived | Puskarich MA, Ingraham NE, Merck LH, Driver BE, Wacker DA, Black LP, Jones AE, Fletcher CV, South AM, Murray TA, Lewandowski C, Farhat J, Benoit JL, Biros MH, Cherabuddi K, Chipman JG, Schacker TW, Guirgis FW, Voelker HT, Koopmeiners JS, Tignanelli CJ; Angiotensin Receptor Blocker Based Lung Protective Strategies for Inpatients With COVID-19 (ALPS-IP) Investigators. Efficacy of Losartan in Hospitalized Patients With COVID-19-Induced Lung Injury: A Randomized Clinical Trial. JAMA Netw Open. 2022 Mar 1;5(3):e222735. doi: 10.1001/jamanetworkopen.2022.2735. | |
| 32658300 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration |
| FG001 | Losartan |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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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 | Apr 22, 2020 |
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| Placebo | Other | Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration |
|
Outcome reported as the number of participants in each arm requiring the use of vasopressors for hypotension. |
| 10 days |
| Proportion of Participants Experiencing Acute Kidney Injury | Outcome reported as the number of participants in each arm who experience acute kidney injury as defined by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines: Increase in serum creatinine by 0.3mg/dL or more within 48 hours OR Increase in serum creatinine to 1.5 times baseline or more within the last 7 days OR Urine output less than 0.5 mL/kg/h for 6 hours. | 10 days |
| Oxygen Saturation / Fractional Inhaled Oxygen (S/F) | Oxygen saturation (percent) is measured by pulse oximeter. Fraction of inspired oxygen (FiO2) (unitless) is the volumetric fraction of oxygen to other gases in respiratory support. The S/F ratio is unitless. | 7 days |
| 28-Day Mortality | Outcome reported as the number of participants who have expired at 28 days post enrollment. | 28 days |
| 90-Day Mortality | Outcome reported as the number of participants who have expired at 90 days post enrollment. | 90 days |
| ICU Admission | Outcome reported as the number of participants in each arm who require admission to the Intensive Care Unit (ICU). | 10 days |
| Number of Ventilator-Free Days | Outcome reported as the mean number of days participants in each arm did not require mechanical ventilation during an in-patient hospital admission. | 28 days |
| Number of Therapeutic Oxygen-Free Days | Outcome reported as the mean number of days participants in each arm did not require therapeutic oxygen usage during an in-patient hospital admission. | 28 days |
| Number of Vasopressor-Free Days | Outcome reported as the mean number of days participants in each arm did not require vasopressor usage during an in-patient hospital admission. | 10 days |
| Length of Hospital Stay | Outcome reported as the mean length of in-patient hospital stay (in days) for participants in each arm. | 90 days |
| Disease Severity Rating | Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities. | 28 days |
| Change in Viral Load by Nasopharyngeal Swab Day 15 | Nasopharyngeal swabs will be collected at baseline and day 15. Viral load is measured as number of viral genetic copies per mL. | 15 days |
| Jacksonville |
| Florida |
| 32209 |
| United States |
| Grady Memorial Hospital | Atlanta | Georgia | 30303 | United States |
| Henry Ford Hospital | Detroit | Michigan | 48202 | United States |
| M Health Fairview Ridges Hospital | Burnsville | Minnesota | 55337 | United States |
| M Health Fairview Southdale Hospital | Edina | Minnesota | 55435 | United States |
| Hennepin County Medical Center | Minneapolis | Minnesota | 55415 | United States |
| M Health Fairview University of Minnesota Medical Center | Minneapolis | Minnesota | 55455 | United States |
| University of Minnesota | Minneapolis | Minnesota | 55455 | United States |
| North Memorial Health Hospital | Robbinsdale | Minnesota | 55422 | United States |
| University of Mississippi Medical Center | Jackson | Mississippi | 39216 | United States |
| Cooper University Hospital | Camden | New Jersey | 08103 | United States |
| University of Cincinnati Medical Center | Cincinnati | Ohio | 45267 | United States |
| Derived |
| Smolander J, Bruchfeld A. [COVID-19 and kidney disease]. Lakartidningen. 2020 Jul 13;117:20110. Swedish. |
Participants in this arm will receive the study drug, Losartan.
Losartan: Losartan; 50 mg daily; oral administration
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration |
| BG001 | Losartan | Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| 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 | Difference in Estimated (PEEP Adjusted) P/F Ratio at 7 Days | Outcome calculated from the partial pressure of oxygen or peripheral saturation of oxygen by pulse oximetry divided by the fraction of inspired oxygen (PaO2 or SaO2 : FiO2 ratio). PaO2 is preferentially used if available. A correction is applied for endotracheal intubation and/or positive end-expiratory pressure. Patients discharged prior to day 7 will have a home pulse oximeter send home for measurement of the day 7 value, and will be adjusted for home O2 use, if applicable. Patients who died will be applied a penalty with a P/F ratio of 0. | Posted | Mean | 95% Confidence Interval | ratio | 7 days |
|
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| |||||||||||||||||||||||||||||
| Secondary | Daily Hypotensive Episodes | Outcome reported as the mean number of daily hypotensive episodes (MAP < 65 mmHg) prompting intervention (indicated by a fluid bolus >=500 mL) per participant in each arm. | Posted | Mean | 95% Confidence Interval | episodes per day | 10 days |
|
| ||||||||||||||||||||||||||||||
| Secondary | Proportion of Participants Requiring Vasopressors for Hypotension | Outcome reported as the number of participants in each arm requiring the use of vasopressors for hypotension. | Posted | Number | proportion of participants | 10 days |
|
| |||||||||||||||||||||||||||||||
| Secondary | Proportion of Participants Experiencing Acute Kidney Injury | Outcome reported as the number of participants in each arm who experience acute kidney injury as defined by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines: Increase in serum creatinine by 0.3mg/dL or more within 48 hours OR Increase in serum creatinine to 1.5 times baseline or more within the last 7 days OR Urine output less than 0.5 mL/kg/h for 6 hours. | Posted | Number | 95% Confidence Interval | proportion of participants | 10 days |
|
| ||||||||||||||||||||||||||||||
| Secondary | Oxygen Saturation / Fractional Inhaled Oxygen (S/F) | Oxygen saturation (percent) is measured by pulse oximeter. Fraction of inspired oxygen (FiO2) (unitless) is the volumetric fraction of oxygen to other gases in respiratory support. The S/F ratio is unitless. | Posted | Mean | 95% Confidence Interval | n/a (ratio) | 7 days |
|
| ||||||||||||||||||||||||||||||
| Secondary | 28-Day Mortality | Outcome reported as the number of participants who have expired at 28 days post enrollment. | Posted | Number | 95% Confidence Interval | proportion of participants | 28 days |
|
| ||||||||||||||||||||||||||||||
| Secondary | 90-Day Mortality | Outcome reported as the number of participants who have expired at 90 days post enrollment. | Posted | Number | 95% Confidence Interval | proportion of participants | 90 days |
|
| ||||||||||||||||||||||||||||||
| Secondary | ICU Admission | Outcome reported as the number of participants in each arm who require admission to the Intensive Care Unit (ICU). | Posted | Number | 95% Confidence Interval | proportion of participants | 10 days |
|
| ||||||||||||||||||||||||||||||
| Secondary | Number of Ventilator-Free Days | Outcome reported as the mean number of days participants in each arm did not require mechanical ventilation during an in-patient hospital admission. | Posted | Mean | 95% Confidence Interval | days | 28 days |
|
| ||||||||||||||||||||||||||||||
| Secondary | Number of Therapeutic Oxygen-Free Days | Outcome reported as the mean number of days participants in each arm did not require therapeutic oxygen usage during an in-patient hospital admission. | Posted | Mean | 95% Confidence Interval | days | 28 days |
|
| ||||||||||||||||||||||||||||||
| Secondary | Number of Vasopressor-Free Days | Outcome reported as the mean number of days participants in each arm did not require vasopressor usage during an in-patient hospital admission. | Posted | Mean | 95% Confidence Interval | days | 10 days |
|
| ||||||||||||||||||||||||||||||
| Secondary | Length of Hospital Stay | Outcome reported as the mean length of in-patient hospital stay (in days) for participants in each arm. | Posted | Median | 95% Confidence Interval | days | 90 days |
|
| ||||||||||||||||||||||||||||||
| Secondary | Disease Severity Rating | Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities. | Posted | Mean | 95% Confidence Interval | score | 28 days |
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| Secondary | Change in Viral Load by Nasopharyngeal Swab Day 15 | Nasopharyngeal swabs will be collected at baseline and day 15. Viral load is measured as number of viral genetic copies per mL. | Posted | Mean | 95% Confidence Interval | log10 copies/mL | 15 days |
|
|
15 days
adverse events were assessed and compared by organ system and not by specific adverse event term
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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 | Placebo | Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration | 11 | 104 | 30 | 104 | 90 | 104 |
| EG001 | Losartan | Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration | 11 | 101 | 36 | 101 | 101 | 101 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiovascular | Cardiac disorders | Non-systematic Assessment |
| ||
| Gastrointestinal | Gastrointestinal disorders | Non-systematic Assessment |
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| Hematologic | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Neurologic | Nervous system disorders | Non-systematic Assessment |
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| Renal | Renal and urinary disorders | Non-systematic Assessment |
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| Respiratory | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiovascular | Cardiac disorders | Non-systematic Assessment |
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| Endocrine | Endocrine disorders | Non-systematic Assessment |
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| Ear, Nose, and Throat | Ear and labyrinth disorders | Non-systematic Assessment |
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| Gastrointestinal | Gastrointestinal disorders | Non-systematic Assessment |
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| Genitourinary | Renal and urinary disorders | Non-systematic Assessment |
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| Hematologic | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Neurologic | Nervous system disorders | Non-systematic Assessment |
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| Renal | Renal and urinary disorders | Non-systematic Assessment |
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| Respiratory | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Skin | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Christopher Tignanelli | University of Minnesota | 612-626-1968 | ctignane@umn.edu |
| Mar 15, 2022 |
| Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Apr 2, 2020 | Mar 15, 2022 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D018352 | Coronavirus Infections |
| D012128 | Respiratory Distress Syndrome |
| D045169 | Severe Acute Respiratory Syndrome |
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D012120 | Respiration Disorders |
| D012141 | Respiratory Tract Infections |
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
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| ID | Term |
|---|---|
| D019808 | Losartan |
| ID | Term |
|---|---|
| D001713 | Biphenyl Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013777 | Tetrazoles |
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| >=65 years |
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| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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