Losartan for Patients With COVID-19 Requiring Hospitalization

• ClinicalTrials.gov Identifier: NCT04312009
• Recruitment Status: Completed
• First Posted: March 17, 2020
• Results First Posted: June 29, 2022
• Last Update Posted: June 29, 2022
• Sponsor: University of Minnesota
• Collaborator: Bill and Melinda Gates Foundation
• Information provided by (Responsible Party): University of Minnesota

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Conditions: Corona Virus Infection; Acute Respiratory Distress Syndrome; SARS-CoV Infection
• Interventions: Drug: Losartan; Other: Placebo
• Enrollment: 205

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Placebo	Losartan
Arm/Group Description	Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
Period Title: Overall Study
Started	104	101
Completed	102	100
Not Completed	2	1
Reason Not Completed
Withdrawal by Subject	2	1

Baseline Characteristics

Arm/Group Title		Placebo	Losartan	Total
Arm/Group Description		Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration	Total of all reporting groups
Overall Number of Baseline Participants		104	101	205
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	104 participants	101 participants	205 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	80 76.9%	78 77.2%	158 77.1%
	>=65 years	24 23.1%	23 22.8%	47 22.9%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	104 participants	101 participants	205 participants
	Female	41 39.4%	41 40.6%	82 40.0%
	Male	63 60.6%	60 59.4%	123 60.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	104 participants	101 participants	205 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	2 1.9%	7 6.9%	9 4.4%
	Native Hawaiian or Other Pacific Islander	1 1.0%	0 0.0%	1 0.5%
	Black or African American	30 28.8%	37 36.6%	67 32.7%
	White	47 45.2%	35 34.7%	82 40.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	24 23.1%	22 21.8%	46 22.4%

Outcome Measures

1. Primary Outcome

Title	Difference in Estimated (PEEP Adjusted) P/F Ratio at 7 Days
Description	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.
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Losartan
Arm/Group Description:	Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
Overall Number of Participants Analyzed	102	100
Mean (95% Confidence Interval); Unit of Measure: ratio
	281.4; (256.7 to 306.1)	260.9; (234.1 to 287.8)

2. Secondary Outcome

Title	Daily Hypotensive Episodes
Description	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.
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Losartan
Arm/Group Description:	Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
Overall Number of Participants Analyzed	102	100
Mean (95% Confidence Interval); Unit of Measure: episodes per day
	0.048; (0.018 to 0.1)	0.119; (0.065 to 0.191)

3. Secondary Outcome

Title	Proportion of Participants Requiring Vasopressors for Hypotension
Description	Outcome reported as the number of participants in each arm requiring the use of vasopressors for hypotension.
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Losartan
Arm/Group Description:	Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
Overall Number of Participants Analyzed	102	100
Measure Type: Number; Unit of Measure: proportion of participants
	0.106	0.198

4. Secondary Outcome

Title	Proportion of Participants Experiencing Acute Kidney Injury
Description	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.
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Losartan
Arm/Group Description:	Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
Overall Number of Participants Analyzed	102	100
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: proportion of participants
	0.106; (0.056 to 0.174)	0.119; (0.065 to 0.191)

5. Secondary Outcome

Title	Oxygen Saturation / Fractional Inhaled Oxygen (S/F)
Description	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.
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Losartan
Arm/Group Description:	Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
Overall Number of Participants Analyzed	102	100
Mean (95% Confidence Interval); Unit of Measure: n/a (ratio)
	357.4; (330.3 to 384.5)	331.5; (302.0 to 361.0)

6. Secondary Outcome

Title	28-Day Mortality
Description	Outcome reported as the number of participants who have expired at 28 days post enrollment.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Losartan
Arm/Group Description:	Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
Overall Number of Participants Analyzed	104	101
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: proportion of participants
	0.087; (0.031 to 0.139)	0.11; (0.047 to 0.169)

7. Secondary Outcome

Title	90-Day Mortality
Description	Outcome reported as the number of participants who have expired at 90 days post enrollment.
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Losartan
Arm/Group Description:	Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
Overall Number of Participants Analyzed	104	101
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: proportion of participants
	0.106; (0.045 to 0.163)	0.11; (0.047 to 0.169)

8. Secondary Outcome

Title	ICU Admission
Description	Outcome reported as the number of participants in each arm who require admission to the Intensive Care Unit (ICU).
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Losartan
Arm/Group Description:	Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
Overall Number of Participants Analyzed	102	100
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: proportion of participants
	0.272; (0.192 to 0.363)	0.36; (0.270 to 0.457)

9. Secondary Outcome

Title	Number of Ventilator-Free Days
Description	Outcome reported as the mean number of days participants in each arm did not require mechanical ventilation during an in-patient hospital admission.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Losartan
Arm/Group Description:	Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
Overall Number of Participants Analyzed	102	100
Mean (95% Confidence Interval); Unit of Measure: days
	18.4; (16.5 to 20.4)	18.1; (16.1 to 20.1)

10. Secondary Outcome

Title	Number of Therapeutic Oxygen-Free Days
Description	Outcome reported as the mean number of days participants in each arm did not require therapeutic oxygen usage during an in-patient hospital admission.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Losartan
Arm/Group Description:	Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
Overall Number of Participants Analyzed	102	100
Mean (95% Confidence Interval); Unit of Measure: days
	24.6; (23.1 to 26.1)	23.6; (21.8 to 25.3)

11. Secondary Outcome

Title	Number of Vasopressor-Free Days
Description	Outcome reported as the mean number of days participants in each arm did not require vasopressor usage during an in-patient hospital admission.
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Losartan
Arm/Group Description:	Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
Overall Number of Participants Analyzed	102	100
Mean (95% Confidence Interval); Unit of Measure: days
	9.4; (9.1 to 9.8)	8.7; (8.2 to 9.3)

12. Secondary Outcome

Title	Length of Hospital Stay
Description	Outcome reported as the mean length of in-patient hospital stay (in days) for participants in each arm.
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Losartan
Arm/Group Description:	Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
Overall Number of Participants Analyzed	104	101
Median (95% Confidence Interval); Unit of Measure: days
	5.9; (4.2 to 7.9)	7.1; (5.2 to 9.1)

13. Secondary Outcome

Title	Disease Severity Rating
Description	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.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Losartan
Arm/Group Description:	Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
Overall Number of Participants Analyzed	102	100
Mean (95% Confidence Interval); Unit of Measure: score
	4.3; (4.0 to 4.6)	4.2; (3.8 to 4.5)

14. Secondary Outcome

Title	Change in Viral Load by Nasopharyngeal Swab Day 15
Description	Nasopharyngeal swabs will be collected at baseline and day 15. Viral load is measured as number of viral genetic copies per mL.
Time Frame	15 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Losartan
Arm/Group Description:	Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
Overall Number of Participants Analyzed	102	100
Mean (95% Confidence Interval); Unit of Measure: log10 copies/mL
	-4.2; (-5.2 to -3.1)	-4.8; (-5.6 to -3.9)

Adverse Events

Time Frame	15 days
Adverse Event Reporting Description	adverse events were assessed and compared by organ system and not by specific adverse event term
Arm/Group Title	Placebo		Losartan
Arm/Group Description	Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration		Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 50 mg daily; oral administration
All-Cause Mortality
	Placebo		Losartan
	Affected / at Risk (%)		Affected / at Risk (%)
Total	11/104 (10.58%)		11/101 (10.89%)
Serious Adverse Events
	Placebo		Losartan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/104 (28.85%)		36/101 (35.64%)
Blood and lymphatic system disorders
Hematologic *	0/104 (0.00%)	0	1/101 (0.99%)	1
Cardiac disorders
Cardiovascular *	6/104 (5.77%)	6	14/101 (13.86%)	14
Gastrointestinal disorders
Gastrointestinal *	0/104 (0.00%)	0	1/101 (0.99%)	1
Nervous system disorders
Neurologic *	1/104 (0.96%)	1	2/101 (1.98%)	2
Renal and urinary disorders
Renal *	2/104 (1.92%)	2	1/101 (0.99%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory *	21/104 (20.19%)	21	19/101 (18.81%)	19
* Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Placebo		Losartan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	90/104 (86.54%)		101/101 (100.00%)
Blood and lymphatic system disorders
Hematologic *	6/104 (5.77%)	6	9/101 (8.91%)	9
Cardiac disorders
Cardiovascular *	24/104 (23.08%)	24	26/101 (25.74%)	26
Ear and labyrinth disorders
Ear, Nose, and Throat *	1/104 (0.96%)	1	0/101 (0.00%)	0
Endocrine disorders
Endocrine *	1/104 (0.96%)	1	2/101 (1.98%)	2
Gastrointestinal disorders
Gastrointestinal *	3/104 (2.88%)	3	10/101 (9.90%)	10
Nervous system disorders
Neurologic *	4/104 (3.85%)	4	4/101 (3.96%)	4
Renal and urinary disorders
Genitourinary *	1/104 (0.96%)	1	3/101 (2.97%)	3
Renal *	21/104 (20.19%)	21	20/101 (19.80%)	20
Respiratory, thoracic and mediastinal disorders
Respiratory *	27/104 (25.96%)	27	30/101 (29.70%)	30
Skin and subcutaneous tissue disorders
Skin *	2/104 (1.92%)	2	0/101 (0.00%)	0
* Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Christopher Tignanelli
• Organization: University of Minnesota
• Phone: 612-626-1968
• EMail: ctignane@umn.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Erratum In: JAMA Netw Open. 2022 May 2;5(5):e2215958.

Smolander J, Bruchfeld A. [COVID-19 and kidney disease]. Lakartidningen. 2020 Jul 13;117:20110. Swedish.

• Responsible Party: University of Minnesota
• ClinicalTrials.gov Identifier: NCT04312009
• Other Study ID Numbers: SURG-2020-28675; INV-017069 ( Other Grant/Funding Number: Bill and Melinda Gates Foundation )
• First Submitted: March 13, 2020
• First Posted: March 17, 2020
• Results First Submitted: March 15, 2022
• Results First Posted: June 29, 2022
• Last Update Posted: June 29, 2022