Trial Outcomes & Findings for Losartan for Patients With COVID-19 Requiring Hospitalization (NCT NCT04312009)

NCT ID: NCT04312009

Last Updated: 2022-06-29

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 205 participants
• Primary outcome timeframe: 7 days
• Results posted on: 2022-06-29

Participant Flow

Participant milestones

Measure	Placebo Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Losartan Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
Overall Study STARTED	104	101
Overall Study COMPLETED	102	100
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Measure	Placebo Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Losartan Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
Overall Study Withdrawal by Subject	2	1

Baseline Characteristics

Losartan for Patients With COVID-19 Requiring Hospitalization

Baseline characteristics by cohort

Measure	Placebo n=104 Participants Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Losartan n=101 Participants Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration	Total n=205 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	80 Participants n=93 Participants	78 Participants n=4 Participants	158 Participants n=27 Participants
Age, Categorical >=65 years	24 Participants n=93 Participants	23 Participants n=4 Participants	47 Participants n=27 Participants
Sex: Female, Male Female	41 Participants n=93 Participants	41 Participants n=4 Participants	82 Participants n=27 Participants
Sex: Female, Male Male	63 Participants n=93 Participants	60 Participants n=4 Participants	123 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	2 Participants n=93 Participants	7 Participants n=4 Participants	9 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) Black or African American	30 Participants n=93 Participants	37 Participants n=4 Participants	67 Participants n=27 Participants
Race (NIH/OMB) White	47 Participants n=93 Participants	35 Participants n=4 Participants	82 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	24 Participants n=93 Participants	22 Participants n=4 Participants	46 Participants n=27 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=102 Participants Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Losartan n=100 Participants Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
Difference in Estimated (PEEP Adjusted) P/F Ratio at 7 Days	281.4 ratio Interval 256.7 to 306.1	260.9 ratio Interval 234.1 to 287.8

SECONDARY outcome

Timeframe: 10 days

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.

Outcome measures

Measure	Placebo n=102 Participants Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Losartan n=100 Participants Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
Daily Hypotensive Episodes	0.048 episodes per day Interval 0.018 to 0.1	0.119 episodes per day Interval 0.065 to 0.191

SECONDARY outcome

Timeframe: 10 days

Outcome reported as the number of participants in each arm requiring the use of vasopressors for hypotension.

Outcome measures

Measure	Placebo n=102 Participants Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Losartan n=100 Participants Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
Proportion of Participants Requiring Vasopressors for Hypotension	0.106 proportion of participants	0.198 proportion of participants

SECONDARY outcome

Timeframe: 10 days

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.

Outcome measures

Measure	Placebo n=102 Participants Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Losartan n=100 Participants Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
Proportion of Participants Experiencing Acute Kidney Injury	0.106 proportion of participants Interval 0.056 to 0.174	0.119 proportion of participants Interval 0.065 to 0.191

SECONDARY outcome

Timeframe: 7 days

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.

Outcome measures

Measure	Placebo n=102 Participants Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Losartan n=100 Participants Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
Oxygen Saturation / Fractional Inhaled Oxygen (S/F)	357.4 n/a (ratio) Interval 330.3 to 384.5	331.5 n/a (ratio) Interval 302.0 to 361.0

SECONDARY outcome

Timeframe: 28 days

Outcome reported as the number of participants who have expired at 28 days post enrollment.

Outcome measures

Measure	Placebo n=104 Participants Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Losartan n=101 Participants Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
28-Day Mortality	0.087 proportion of participants Interval 0.031 to 0.139	0.11 proportion of participants Interval 0.047 to 0.169

SECONDARY outcome

Timeframe: 90 days

Outcome reported as the number of participants who have expired at 90 days post enrollment.

Outcome measures

Measure	Placebo n=104 Participants Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Losartan n=101 Participants Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
90-Day Mortality	0.106 proportion of participants Interval 0.045 to 0.163	0.11 proportion of participants Interval 0.047 to 0.169

SECONDARY outcome

Timeframe: 10 days

Outcome reported as the number of participants in each arm who require admission to the Intensive Care Unit (ICU).

Outcome measures

Measure	Placebo n=102 Participants Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Losartan n=100 Participants Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
ICU Admission	0.272 proportion of participants Interval 0.192 to 0.363	0.36 proportion of participants Interval 0.27 to 0.457

SECONDARY outcome

Timeframe: 28 days

Outcome reported as the mean number of days participants in each arm did not require mechanical ventilation during an in-patient hospital admission.

Outcome measures

Measure	Placebo n=102 Participants Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Losartan n=100 Participants Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
Number of Ventilator-Free Days	18.4 days Interval 16.5 to 20.4	18.1 days Interval 16.1 to 20.1

SECONDARY outcome

Timeframe: 28 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.

Outcome measures

Measure	Placebo n=102 Participants Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Losartan n=100 Participants Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
Number of Therapeutic Oxygen-Free Days	24.6 days Interval 23.1 to 26.1	23.6 days Interval 21.8 to 25.3

SECONDARY outcome

Timeframe: 10 days

Outcome reported as the mean number of days participants in each arm did not require vasopressor usage during an in-patient hospital admission.

Outcome measures

Measure	Placebo n=102 Participants Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Losartan n=100 Participants Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
Number of Vasopressor-Free Days	9.4 days Interval 9.1 to 9.8	8.7 days Interval 8.2 to 9.3

SECONDARY outcome

Timeframe: 90 days

Outcome reported as the mean length of in-patient hospital stay (in days) for participants in each arm.

Outcome measures

Measure	Placebo n=104 Participants Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Losartan n=101 Participants Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
Length of Hospital Stay	5.9 days Interval 4.2 to 7.9	7.1 days Interval 5.2 to 9.1

SECONDARY outcome

Timeframe: 28 days

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.

Outcome measures

Measure	Placebo n=102 Participants Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Losartan n=100 Participants Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
Disease Severity Rating	4.3 score Interval 4.0 to 4.6	4.2 score Interval 3.8 to 4.5

SECONDARY outcome

Timeframe: 15 days

Nasopharyngeal swabs will be collected at baseline and day 15. Viral load is measured as number of viral genetic copies per mL.

Outcome measures

Measure	Placebo n=102 Participants Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Losartan n=100 Participants Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
Change in Viral Load by Nasopharyngeal Swab Day 15	-4.2 log10 copies/mL Interval -5.2 to -3.1	-4.8 log10 copies/mL Interval -5.6 to -3.9

Adverse Events

Placebo

Serious events: 30 serious events

Other events: 90 other events

Deaths: 11 deaths

Losartan

Serious events: 36 serious events

Other events: 101 other events

Deaths: 11 deaths

Serious adverse events

Measure	Placebo n=104 participants at risk Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Losartan n=101 participants at risk Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
Cardiac disorders Cardiovascular	5.8% 6/104 • Number of events 6 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term	13.9% 14/101 • Number of events 14 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term
Gastrointestinal disorders Gastrointestinal	0.00% 0/104 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term	0.99% 1/101 • Number of events 1 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term
Blood and lymphatic system disorders Hematologic	0.00% 0/104 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term	0.99% 1/101 • Number of events 1 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term
Nervous system disorders Neurologic	0.96% 1/104 • Number of events 1 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term	2.0% 2/101 • Number of events 2 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term
Renal and urinary disorders Renal	1.9% 2/104 • Number of events 2 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term	0.99% 1/101 • Number of events 1 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term
Respiratory, thoracic and mediastinal disorders Respiratory	20.2% 21/104 • Number of events 21 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term	18.8% 19/101 • Number of events 19 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term

Other adverse events

Measure	Placebo n=104 participants at risk Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Losartan n=101 participants at risk Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
Cardiac disorders Cardiovascular	23.1% 24/104 • Number of events 24 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term	25.7% 26/101 • Number of events 26 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term
Endocrine disorders Endocrine	0.96% 1/104 • Number of events 1 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term	2.0% 2/101 • Number of events 2 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term
Ear and labyrinth disorders Ear, Nose, and Throat	0.96% 1/104 • Number of events 1 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term	0.00% 0/101 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term
Gastrointestinal disorders Gastrointestinal	2.9% 3/104 • Number of events 3 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term	9.9% 10/101 • Number of events 10 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term
Renal and urinary disorders Genitourinary	0.96% 1/104 • Number of events 1 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term	3.0% 3/101 • Number of events 3 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term
Blood and lymphatic system disorders Hematologic	5.8% 6/104 • Number of events 6 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term	8.9% 9/101 • Number of events 9 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term
Nervous system disorders Neurologic	3.8% 4/104 • Number of events 4 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term	4.0% 4/101 • Number of events 4 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term
Renal and urinary disorders Renal	20.2% 21/104 • Number of events 21 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term	19.8% 20/101 • Number of events 20 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term
Respiratory, thoracic and mediastinal disorders Respiratory	26.0% 27/104 • Number of events 27 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term	29.7% 30/101 • Number of events 30 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term
Skin and subcutaneous tissue disorders Skin	1.9% 2/104 • Number of events 2 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term	0.00% 0/101 • 15 days adverse events were assessed and compared by organ system and not by specific adverse event term

Additional Information

Christopher Tignanelli

University of Minnesota

Phone: 612-626-1968

Email: ctignane@umn.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place