Losartan for Patients With COVID-19 Not Requiring Hospitalization

• ClinicalTrials.gov Identifier: NCT04311177
• Recruitment Status: Completed
• First Posted: March 17, 2020
• Results First Posted: May 4, 2022
• Last Update Posted: May 4, 2022
• Sponsor: University of Minnesota
• 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: 117

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Losartan	Placebo
Arm/Group Description	Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 25 mg daily; oral administration	Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration
Period Title: Overall Study
Started	58	59
Completed	50	55
Not Completed	8	4
Reason Not Completed
Adverse Event	3	1
Physician Decision	4	3
Withdrawal by Subject	1	0

Baseline Characteristics

Arm/Group Title		Losartan	Placebo	Total
Arm/Group Description		Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 25 mg daily; oral administration	Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration	Total of all reporting groups
Overall Number of Baseline Participants		58	59	117
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	58 participants	59 participants	117 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	55 94.8%	59 100.0%	114 97.4%
	>=65 years	3 5.2%	0 0.0%	3 2.6%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	58 participants	59 participants	117 participants
	Female	33 56.9%	25 42.4%	58 49.6%
	Male	25 43.1%	34 57.6%	59 50.4%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	58 participants	59 participants	117 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	1 1.7%	5 8.5%	6 5.1%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	4 6.9%	4 6.8%	8 6.8%
	White	45 77.6%	40 67.8%	85 72.6%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	8 13.8%	10 16.9%	18 15.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Admitted to the Hospital
Description	Outcome reported as the percentage of participants per arm admitted to inpatient hospital care due to COVID-19-related disease within 15 days of randomization. Currently, there is a pre-planned pooled analysis with a national trial network under development.
Time Frame	15 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Losartan	Placebo
Arm/Group Description:	Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 25 mg daily; oral administration	Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration
Overall Number of Participants Analyzed	58	59
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	5.2; (1.1 to 14.4)	1.7; (0.0 to 9.1)

2. Secondary Outcome

Title	Change in PROMIS Dyspnea Scale
Description	The PROMIS dyspnea scale consists of 4 subscales. 3 (1. general shortness of breath, 2. intensity, and 3. Frequency) are scored from 0 (no symptoms) to 10 (most severe). The 4th subscale is scored from 0-4 in response to the question "I've been short of breath" with 0 representing none and 4 the most severe, for a total range of 0-34. Results are difference between enrollment and day 10. There are no units.
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

Only 50 patients were analyzed for this outcome measure due to loss to follow-up or refusal to complete the survey resulting in data missingness.

Arm/Group Title	Losartan	Placebo
Arm/Group Description:	Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 25 mg daily; oral administration	Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration
Overall Number of Participants Analyzed	50	50
Mean (Standard Deviation); Unit of Measure: score on a scale
	-0.4 (0.9)	-0.5 (0.7)

3. Secondary Outcome

Title	Change in SF-12 Physical Composite Score
Description	The SF-12 is a self-reported validated outcome measure assessing the impact of health on an individual's everyday life. Patients fill out a 12 question survey which is then scored by a clinician or researcher. Physical score is computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. The 33-item Severity bank assesses the severity of difficulty breathing during various specific activities (the same 33 activities assessed in Dyspnea Functional Limitations). Each activity is rated in terms of degree of dyspnea (0 = no shortness of breath, 1 = mildly short of breath, 2 = moderately short of breath, 3 = severely short of breath) while engaging in the activity over the past 7 days. Total scores range from 0 to 99 with higher scores reflecting greater levels of dyspnea during daily activity.
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Losartan	Placebo
Arm/Group Description:	Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 25 mg daily; oral administration	Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration
Overall Number of Participants Analyzed	31	39
Mean (Standard Deviation); Unit of Measure: score
	1.4 (9.1)	0.2 (6.5)

4. Secondary Outcome

Title	Change in SF-12 Mental Composite Score
Description	The SF-12 is a self-reported validated outcome measure assessing the impact of health on an individual's everyday life. Patients fill out a 12 question survey which is then scored by a clinician or researcher. Mental composite score is computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Losartan	Placebo
Arm/Group Description:	Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 25 mg daily; oral administration	Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration
Overall Number of Participants Analyzed	31	39
Mean (Standard Deviation); Unit of Measure: score
	-0.1 (6.5)	-0.3 (5.7)

5. Secondary Outcome

Title	Daily Maximum Temperature
Description	Participants will report their maximum daily oral temperature to the study team. Outcome is reported as the mean maximum daily body temperature (in degrees Celsius) over 10 days.
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Losartan	Placebo
Arm/Group Description:	Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 25 mg daily; oral administration	Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration
Overall Number of Participants Analyzed	58	59
Mean (Standard Error); Unit of Measure: degrees Farenheit
	97.7 (0.097)	97.8 (0.092)

6. Secondary Outcome

Title	Count of Participants With an Emergency Department or Clinic Presentation
Description	Outcome is reported as the mean number of emergency department and clinic presentations combined per participant in each arm.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Losartan	Placebo
Arm/Group Description:	Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 25 mg daily; oral administration	Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration
Overall Number of Participants Analyzed	58	59
Measure Type: Count of Participants; Unit of Measure: Participants
	10 17.2%	5 8.5%

7. Secondary Outcome

Title	Disease Severity Rating Day 15
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	15 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Losartan	Placebo
Arm/Group Description:	Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 25 mg daily; oral administration	Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration
Overall Number of Participants Analyzed	58	59
Mean (Standard Deviation); Unit of Measure: score
	5.8 (0.5)	5.9 (0.7)

8. Secondary Outcome

Title	Change in Viral Load by Nasopharyngeal Swab at Day 9
Description	Viral load is measured as number of viral genetic copies per mL.
Time Frame	9 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Losartan	Placebo
Arm/Group Description:	Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 25 mg daily; oral administration	Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration
Overall Number of Participants Analyzed	32	35
Mean (Standard Error); Unit of Measure: log10 copies/mL
	-3.8 (0.3)	-3.6 (0.29)

9. Secondary Outcome

Title	Change in Viral Load by Nasopharyngeal Swab at Day 15
Description	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	Losartan	Placebo
Arm/Group Description:	Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 25 mg daily; oral administration	Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration
Overall Number of Participants Analyzed	35	25
Mean (Standard Error); Unit of Measure: log10 copies/mL
	-3.7 (0.33)	-4 (0.29)

10. Secondary Outcome

Title	Percentage of Patients Admitted to the Intensive Care Unit Within 15 Days
Description	Outcome reported as the percent of participants in each arm who require ICU admission by day 15 following randomization.
Time Frame	15 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Losartan	Placebo
Arm/Group Description:	Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 25 mg daily; oral administration	Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration
Overall Number of Participants Analyzed	58	59
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	1.7; (0.0 to 9.2)	1.7; (0.0 to 9.1)

11. Secondary Outcome

Title	Need for Oxygen Therapy at 15 Days
Description	Outcome reported as the percent of participants in each arm who require oxygen therapy by day 15 following randomization.
Time Frame	15 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Losartan	Placebo
Arm/Group Description:	Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 25 mg daily; oral administration	Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration
Overall Number of Participants Analyzed	58	59
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	1.7; (0.0 to 9.2)	1.7; (0.0 to 9.1)

Adverse Events

Time Frame	28 days
Adverse Event Reporting Description	Events were monitored / assessed without regard to specific adverse event term, but rather by systems.
Arm/Group Title	Losartan		Placebo
Arm/Group Description	Participants in this arm will receive the study drug, Losartan. Losartan: Losartan; 25 mg daily; oral administration		Participants in this arm will receive a placebo treatment. Placebo: Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration
All-Cause Mortality
	Losartan		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/58 (0.00%)		0/59 (0.00%)
Serious Adverse Events
	Losartan		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/58 (5.17%)		1/59 (1.69%)
Respiratory, thoracic and mediastinal disorders
Hospital Admission *	3/58 (5.17%)	3	1/59 (1.69%)	1
* Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Losartan		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/58 (74.14%)		56/59 (94.92%)
Cardiac disorders
Cardiovascular *	9/58 (15.52%)	9	6/59 (10.17%)	6
Ear and labyrinth disorders
Ear, Nose, and Throat *	7/58 (12.07%)	7	4/59 (6.78%)	4
Gastrointestinal disorders
Gastrointestinal *	4/58 (6.90%)	4	4/59 (6.78%)	4
Nervous system disorders
Neurologic *	3/58 (5.17%)	3	2/59 (3.39%)	2
Renal and urinary disorders
Renal *	2/58 (3.45%)	2	5/59 (8.47%)	5
Respiratory, thoracic and mediastinal disorders
Respiratory *	9/58 (15.52%)	9	22/59 (37.29%)	22
Skin and subcutaneous tissue disorders
Skin *	3/58 (5.17%)	3	0/59 (0.00%)	0
Social circumstances
Constitutional *	6/58 (10.34%)	6	13/59 (22.03%)	13
* 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 of Results:

Puskarich MA, Cummins NW, Ingraham NE, Wacker DA, Reilkoff RA, Driver BE, Biros MH, Bellolio F, Chipman JG, Nelson AC, Beckman K, Langlois R, Bold T, Aliota MT, Schacker TW, Voelker HT, Murray TA, Koopmeiners JS, Tignanelli CJ. A multi-center phase II randomized clinical trial of losartan on symptomatic outpatients with COVID-19. EClinicalMedicine. 2021 Jun 17;37:100957. doi: 10.1016/j.eclinm.2021.100957. eCollection 2021 Jul.

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

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

• Responsible Party: University of Minnesota
• ClinicalTrials.gov Identifier: NCT04311177
• Other Study ID Numbers: SURG-2020-28683
• First Submitted: March 13, 2020
• First Posted: March 17, 2020
• Results First Submitted: March 16, 2022
• Results First Posted: May 4, 2022
• Last Update Posted: May 4, 2022