Losartan for Patients With COVID-19 Not Requiring Hospitalization

• Sponsor: University of Minnesota (Other)
• Overall Status: Completed
• CT.gov ID: NCT04311177
• Collaborator: (none)
• Enrollment: 117
• Locations: 4
• Arms: 2
• Actual Duration (Months): 9.8
• Patients Per Site: 29.3
• Patients Per Site Per Month: 3

Study Details

Study Description

Brief Summary

This is a multi-center, double-blinded study of COVID-19 infected patients randomized 1:1 to daily losartan or placebo for 10 days or treatment failure (hospital admission).

Condition or Disease	Intervention/Treatment	Phase
Corona Virus Infection; Acute Respiratory Distress Syndrome; SARS-CoV Infection	Drug: Losartan; Other: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 117 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized Controlled Trial of Losartan for Patients With COVID-19 Not Requiring Hospitalization
• Actual Study Start Date: Apr 9, 2020
• Actual Primary Completion Date: Feb 1, 2021
• Actual Study Completion Date: Feb 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Losartan Participants in this arm will receive the study drug, Losartan.	Drug: Losartan; Losartan; 25 mg daily; oral administration; Other Names: Cozaar
Placebo Comparator: Placebo Participants in this arm will receive a placebo treatment.	Other: Placebo; Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Admitted to the Hospital [15 days]

   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.

Secondary Outcome Measures

1. Change in PROMIS Dyspnea Scale [10 days]

   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.

2. Change in SF-12 Physical Composite Score [10 days]

   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.

3. Change in SF-12 Mental Composite Score [10 days]

   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.

4. Daily Maximum Temperature [10 days]

   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.

5. Count of Participants With an Emergency Department or Clinic Presentation [28 days]

   Outcome is reported as the mean number of emergency department and clinic presentations combined per participant in each arm.

6. Disease Severity Rating Day 15 [15 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.

7. Change in Viral Load by Nasopharyngeal Swab at Day 9 [9 days]

   Viral load is measured as number of viral genetic copies per mL.

8. Change in Viral Load by Nasopharyngeal Swab at Day 15 [15 days]

   Viral load is measured as number of viral genetic copies per mL.

9. Percentage of Patients Admitted to the Intensive Care Unit Within 15 Days [15 days]

   Outcome reported as the percent of participants in each arm who require ICU admission by day 15 following randomization.

10. Need for Oxygen Therapy at 15 Days [15 days]

    Outcome reported as the percent of participants in each arm who require oxygen therapy by day 15 following randomization.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Positive laboratory test for COVID-19 based on local laboratory standard

• Age greater than or equal to 18 years of age

• One of the following: Upper respiratory symptoms (cough, rhinorrhea) or fever (>101.5) or loss of taste / smell

Exclusion Criteria:

• Randomization > 72 hours of meeting inclusion criteria

• Randomization > 7 days of symptom onset

• 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 women

• Females able to have children 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, condom use or abstinence during the study. All participants of child bearing potential enrolled in this fashion will be informed of the teratogenic risks.

• Patient reported history or electronic medical record history of kidney disease, defined as:

1. Any history of dialysis

2. History of chronic kidney disease stage IV

3. Estimated Glomerular Filtration Rate (eGFR) of < 30ml/min/1.73 m2 (must be have been measured within 1 month of enrollment)

4. Other kidney disease that in the opinion of the investigator, would affect losartan clearance

• Patient reported dehydration and significantly decreased urine output in the past 72 hours

• Most recent systolic blood pressure prior to enrollment <110 mmHg

• Patient reported history or electronic medical record history of severe liver disease, defined as:

1. Cirrhosis

2. History of hepatitis B or C

3. Other liver disease that in the opinion of the investigator, would affect losartan clearance

4. Documented AST or ALT > 3 times the upper limit of normal within 3 months of randomization (if available in electronic medical record)

• Potassium >5.0 mmol/L (must have been measured within 1 month) of enrollment

• Concurrent treatment with aliskiren

• Inability to obtain informed consent

• Enrollment in another blinded randomized clinical trial for COVID

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
2	M Health Fairview University of Minnesota Medical Center	Minneapolis	Minnesota	United States	55455
3	University of Minnesota	Minneapolis	Minnesota	United States	55455
4	Mayo Clinic Health System	Rochester	Minnesota	United States	55415

Sponsors and Collaborators

• University of Minnesota

Investigators

• Principal Investigator: Christopher Tignanelli, MD, University of Minnesota
• Principal Investigator: Michael Puskarich, MD, MS, University of Minnesota

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 5, 2020
• Informed Consent Form - Apr 7, 2020

More Information

Publications

None provided.

• Responsible Party: University of Minnesota
• ClinicalTrials.gov Identifier: NCT04311177
• Other Study ID Numbers: SURG-2020-28683
• First Posted: Mar 17, 2020
• Last Update Posted: May 4, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by University of Minnesota: COVID-19; Corona Virus; SARS-COV-2
• Additional relevant MeSH terms: Infections; Communicable Diseases; COVID-19; Coronavirus Infections; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Losartan

Study Results

Participant Flow

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

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 Participants	58	59	117
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	55 94.8%	59 100%	114 97.4%
>=65 years	3 5.2%	0 0%	3 2.6%
Sex: Female, Male (Count of Participants)
Female	33 56.9%	25 42.4%	58 49.6%
Male	25 43.1%	34 57.6%	59 50.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	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%
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%
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
Measure Participants	58	59
Number (95% Confidence Interval) [percentage of participants]	5.2 9%	1.7 2.9%

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
Measure Participants	50	50
Mean (Standard Deviation) [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
Measure Participants	31	39
Mean (Standard Deviation) [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
Measure Participants	31	39
Mean (Standard Deviation) [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
Measure Participants	58	59
Mean (Standard Error) [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
Measure Participants	58	59
Count of Participants [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
Measure Participants	58	59
Mean (Standard Deviation) [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
Measure Participants	32	35
Mean (Standard Error) [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
Measure Participants	35	25
Mean (Standard Error) [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
Measure Participants	58	59
Number (95% Confidence Interval) [percentage of participants]	1.7 2.9%	1.7 2.9%

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
Measure Participants	58	59
Number (95% Confidence Interval) [percentage of participants]	1.7 2.9%	1.7 2.9%

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 (%)	# Events	Affected / at Risk (%)	# Events
Total	0/58 (0%)		0/59 (0%)
Serious Adverse Events
	Losartan		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/58 (5.2%)		1/59 (1.7%)
Respiratory, thoracic and mediastinal disorders
Hospital Admission	3/58 (5.2%)	3	1/59 (1.7%)	1
Other (Not Including Serious) Adverse Events
	Losartan		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/58 (74.1%)		56/59 (94.9%)
Cardiac disorders
Cardiovascular	9/58 (15.5%)	9	6/59 (10.2%)	6
Ear and labyrinth disorders
Ear, Nose, and Throat	7/58 (12.1%)	7	4/59 (6.8%)	4
Gastrointestinal disorders
Gastrointestinal	4/58 (6.9%)	4	4/59 (6.8%)	4
Nervous system disorders
Neurologic	3/58 (5.2%)	3	2/59 (3.4%)	2
Renal and urinary disorders
Renal	2/58 (3.4%)	2	5/59 (8.5%)	5
Respiratory, thoracic and mediastinal disorders
Respiratory	9/58 (15.5%)	9	22/59 (37.3%)	22
Skin and subcutaneous tissue disorders
Skin	3/58 (5.2%)	3	0/59 (0%)	0
Social circumstances
Constitutional	6/58 (10.3%)	6	13/59 (22%)	13

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.