Do Angiotensin Receptor Blockers Mitigate Progression to Acute Respiratory Distress Syndrome With SARS-CoV-2 Infection

• Sponsor: Sharp HealthCare (Other)
• Overall Status: Completed
• CT.gov ID: NCT04340557
• Collaborator: (none)
• Enrollment: 31
• Locations: 3
• Arms: 2
• Actual Duration (Months): 2.6
• Patients Per Site: 10.3
• Patients Per Site Per Month: 4

Study Details

Study Description

Brief Summary

The purpose of this research is to identify whether or not Angiotensin Receptor Blockers (ARB) can halt the progression to respiratory failure requiring transfer into the intensive care unit (ICU), as well as halt mechanical ventilation in subjects with mild to moderate hypoxia due to the corona virus that causes COVID-19. Based on previous animal studies, the researchers hypothesize that the addition of an ARB is beneficial in abating acute lung injury in subjects in early stages of SARS-CoV-2 viral induced hypoxia.

Condition or Disease	Intervention/Treatment	Phase
SARS-CoV Infection	Drug: Losartan	Phase 4

Detailed Description

This is an investigator initiated, open label, multicenter, two arm, randomized study to compare the impact of adding an ARB to the Standard of Care (SOC) to the SOC without an ARB. Randomization ratio will be 1:1. The goal of this study is to identify whether or not ARBs have an impact on inhibiting the progression to respiratory failure requiring mechanical ventilation in patients with mild to moderate hypoxia in the setting of COVID-19. The addition of an ARB to the standard of care treatment for these patients may be beneficial in abating acute lung injury in patients in early stages of SARS-CoV-2 induced hypoxia.

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Subjects will be randomized into one of two groups: Standard of Care or Standard of Care plus an ARB.Subjects will be randomized into one of two groups: Standard of Care or Standard of Care plus an ARB.
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Randomized Open Label Study of Standard of Care Plus an Angiotensin II Receptor Blocker Compared to Standard of Care Alone to Minimize the Progression to Respiratory Failure in SARS-CoV-2 Infection
• Actual Study Start Date: Mar 27, 2020
• Actual Primary Completion Date: Jun 13, 2020
• Actual Study Completion Date: Jun 13, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A (Study drug+SOC) Standard of Care plus an ARB to be taken orally twice daily for up to 10 days or until discharged from the hospital, whichever occurs first. Investigator may increase dose on days 2 - 10 if confident the subject will tolerate.	Drug: Losartan; Standard of care plus the starting dose of losartan 12.5mg (investigator has option to increase dose on days 2-10 based on tolerance of SBP) of losartan taken twice daily for up to 10 days. Upon the treating clinician's discretion, losartan may be continued beyond 10 days for non-COVID-19 indications.; Other Names: Losartan + Standard of Care
No Intervention: Group B (SOC) Standard of Care

Outcome Measures

Primary Outcome Measures

1. Mechanical Ventilation [from date of patient admission to date of patient discharge or date of death, whichever came first, assessed up to 45 days]

   Number of subjects requiring transfer into ICU for mechanical ventilation due to respiratory failure

Secondary Outcome Measures

1. ICU Transfer [from date of patient admission to date of patient discharge or date of death, whichever came first, assessed up to 45 days]

   Number of subjects transferred from non-ICU bed to an ICU bed

2. Oxygen Therapy [from date of patient admission to date of patient discharge or date of death, whichever came first, assessed up to 45 days]

   Mean number of liters of oxygen consumed

Other Outcome Measures

1. Length of Hospital Stay [from date of patient admission to date of patient discharge or date of death, whichever came first, assessed up to 45 days]

   Length of hospital stay from admission to discharge

2. In Hospital Mortality [from date of patient admission to date of patient discharge or date of death, whichever came first, assessed up to 45 days]

   Number of subjects who expired while hospitalized

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Confirmed COVID-19 positive test result

• Mild to moderate respiratory symptoms of COVID-19.

• Systolic blood pressure ≥ 105 mmHg.

• Screen within 3 days of a positive COVID-19 test.

• Age ≥18 years old.

• Access to a phone in the hospital room or an electronic device that is capable of receiving phone or video calls.

• Able to read/write/speak English or Spanish fluently.

• Subjects must have the capacity to provide consent or an appropriate LAR to provide informed consent.

• Negative pregnancy test for women of childbearing potential and subject is randomized to the study arm.

Exclusion Criteria:

• Severe allergy to any ARB or ACE-inhibitor, including angioedema

• In the intensive care unit at screening.

• Home meds include any kind of ACE inhibitor or ARB

• Acute Kidney Injury (50% reduction in GFR from baseline at admission to any time during treatment in the study treatment arm)

• Hyperkalemia >5.0 mmol/L at baseline or any time during treatment in the study treatment arm

• Creatinine Clearance < 30 ml/min at baseline or any time during treatment in the study treatment arm

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sharp Grossmont Hospital	La Mesa	California	United States	91942
2	Sharp Chula Vista Medical Center	San Diego	California	United States	91911
3	Sharp Memorial Hospital	San Diego	California	United States	92123

Sponsors and Collaborators

• Sharp HealthCare

Investigators

• Study Director: Matthew Geriak, PharmD, Sharp HealthCare

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 20, 2020

More Information

Publications

None provided.

• Responsible Party: Matthew Geriak, Investigational Pharmacist, Sharp HealthCare
• ClinicalTrials.gov Identifier: NCT04340557
• Other Study ID Numbers: COVID-ARB; 2003902
• First Posted: Apr 9, 2020
• Last Update Posted: May 26, 2021
• Last Verified: May 1, 2021

• 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 Matthew Geriak, Investigational Pharmacist, Sharp HealthCare: Coronavirus; Angiotensin receptor blocker; SARS-CoV-2; COVID-19
• Additional relevant MeSH terms: Infections; Communicable Diseases; COVID-19; Severe Acute Respiratory Syndrome; Losartan

Study Results

Participant Flow

Arm/Group Title	Losartan + Standard of Care	Standard of Care
Arm/Group Description	Standard of Care plus an ARB to be taken orally twice daily for up to 10 days or until discharged from the hospital, whichever occurs first. Investigator may increase dose on days 2 - 10 if confident the subject will tolerate. Losartan: Standard of care plus the starting dose of losartan 12.5mg (investigator has option to increase dose on days 2-10 based on tolerance of SBP) of losartan taken twice daily for up to 10 days.	Patient will receive the hospital Standard of Care for their condition
Period Title: Overall Study
STARTED	16	15
COMPLETED	15	13
NOT COMPLETED	1	2

Baseline Characteristics

Arm/Group Title	Group A (Study Drug+SOC)	Group B (SOC)	Total
Arm/Group Description	Standard of Care plus an ARB to be taken orally twice daily for up to 10 days or until discharged from the hospital, whichever occurs first. Investigator may increase dose on days 2 - 10 if confident the subject will tolerate. Losartan: Standard of care plus the starting dose of losartan 12.5mg (investigator has option to increase dose on days 2-10 based on tolerance of SBP) of losartan taken twice daily for up to 10 days.	Standard of Care	Total of all reporting groups
Overall Participants	16	15	31
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	59.3	54.9	57.1
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	54	53	53
Sex: Female, Male (Count of Participants)
Female	6 37.5%	6 40%	12 38.7%
Male	10 62.5%	9 60%	19 61.3%
Race/Ethnicity, Customized (Count of Participants)
White	1 6.3%	2 13.3%	3 9.7%
Black/African America	1 6.3%	0 0%	1 3.2%
Hispanic	12 75%	13 86.7%	25 80.6%
Asian	0 0%	0 0%	0 0%
Unknown	2 12.5%	0 0%	2 6.5%
Days from Hospital Admission to Enrollment (days) [Median (Full Range) ]
Median (Full Range) [days]	2	2	2
Charlson Comorbidity Index (scores on a scale) [Mean (Full Range) ]
Mean (Full Range) [scores on a scale]	2.06	1.87	1.97
Comorbidities (Count of Participants)
Diabetes mellitus	3 18.8%	5 33.3%	8 25.8%
Hypertension	7 43.8%	5 33.3%	12 38.7%
Obesity (BMI >/= 30 kg/m^2)	8 50%	5 33.3%	13 41.9%
Tobacco Use	4 25%	2 13.3%	6 19.4%
Cardiovascular Disease	1 6.3%	0 0%	1 3.2%
Receipt of Concomitant SARS-CoV-2 Medications (Count of Participants)
Remdesivir	4 25%	5 33.3%	9 29%
Glucocorticoids > 2 doses	2 12.5%	5 33.3%	7 22.6%
Azithromycin	2 12.5%	3 20%	5 16.1%
Hydroxychloroquine	2 12.5%	1 6.7%	3 9.7%
Convalescent Plasma	1 6.3%	1 6.7%	2 6.5%
Anti-thrombotics	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Mechanical Ventilation
Description	Number of subjects requiring transfer into ICU for mechanical ventilation due to respiratory failure
Time Frame	from date of patient admission to date of patient discharge or date of death, whichever came first, assessed up to 45 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A (Study Drug+SOC)	Group B (SOC)
Arm/Group Description	Standard of Care plus an ARB to be taken orally twice daily for up to 10 days or until discharged from the hospital, whichever occurs first. Investigator may increase dose on days 2 - 10 if confident the subject will tolerate. Losartan: Standard of care plus the starting dose of losartan 12.5mg (investigator has option to increase dose on days 2-10 based on tolerance of SBP) of losartan taken twice daily for up to 10 days.	Standard of Care
Measure Participants	16	15
Count of Participants [Participants]	1 6.3%	1 6.7%

2. Secondary Outcome

Title	ICU Transfer
Description	Number of subjects transferred from non-ICU bed to an ICU bed
Time Frame	from date of patient admission to date of patient discharge or date of death, whichever came first, assessed up to 45 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A (Study Drug+SOC)	Group B (SOC)
Arm/Group Description	Standard of Care plus an ARB to be taken orally twice daily for up to 10 days or until discharged from the hospital, whichever occurs first. Investigator may increase dose on days 2 - 10 if confident the subject will tolerate. Losartan: Standard of care plus the starting dose of losartan 12.5mg (investigator has option to increase dose on days 2-10 based on tolerance of SBP) of losartan taken twice daily for up to 10 days.	Standard of Care
Measure Participants	16	15
Count of Participants [Participants]	1 6.3%	2 13.3%

3. Secondary Outcome

Title	Oxygen Therapy
Description	Mean number of liters of oxygen consumed
Time Frame	from date of patient admission to date of patient discharge or date of death, whichever came first, assessed up to 45 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A (Study Drug+SOC)	Group B (SOC)
Arm/Group Description	Standard of Care plus an ARB to be taken orally twice daily for up to 10 days or until discharged from the hospital, whichever occurs first. Investigator may increase dose on days 2 - 10 if confident the subject will tolerate. Losartan: Standard of care plus the starting dose of losartan 12.5mg (investigator has option to increase dose on days 2-10 based on tolerance of SBP) of losartan taken twice daily for up to 10 days.	Standard of Care
Measure Participants	16	15
Mean (Full Range) [liters]	10,469	82,734

4. Other Pre-specified Outcome

Title	Length of Hospital Stay
Description	Length of hospital stay from admission to discharge
Time Frame	from date of patient admission to date of patient discharge or date of death, whichever came first, assessed up to 45 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A (Study Drug+SOC)	Group B (SOC)
Arm/Group Description	Standard of Care plus an ARB to be taken orally twice daily for up to 10 days or until discharged from the hospital, whichever occurs first. Investigator may increase dose on days 2 - 10 if confident the subject will tolerate. Losartan: Standard of care plus the starting dose of losartan 12.5mg (investigator has option to increase dose on days 2-10 based on tolerance of SBP) of losartan taken twice daily for up to 10 days.	Standard of Care
Measure Participants	16	15
Mean (Full Range) [days]	9	10

5. Other Pre-specified Outcome

Title	In Hospital Mortality
Description	Number of subjects who expired while hospitalized
Time Frame	from date of patient admission to date of patient discharge or date of death, whichever came first, assessed up to 45 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A (Study Drug+SOC)	Group B (SOC)
Arm/Group Description	Standard of Care plus an ARB to be taken orally twice daily for up to 10 days or until discharged from the hospital, whichever occurs first. Investigator may increase dose on days 2 - 10 if confident the subject will tolerate. Losartan: Standard of care plus the starting dose of losartan 12.5mg (investigator has option to increase dose on days 2-10 based on tolerance of SBP) of losartan taken twice daily for up to 10 days.	Standard of Care
Measure Participants	16	15
Count of Participants [Participants]	1 6.3%	1 6.7%

Adverse Events

Time Frame	From enrollment into the study until hospital discharge or death, assessed up to 45 days.
Arm/Group Title	Group A (Study Drug+SOC)		Group B (SOC)
Arm/Group Description	Standard of Care plus an ARB to be taken orally twice daily for up to 10 days or until discharged from the hospital, whichever occurs first. Investigator may increase dose on days 2 - 10 if confident the subject will tolerate. Losartan: Standard of care plus the starting dose of losartan 12.5mg (investigator has option to increase dose on days 2-10 based on tolerance of SBP) of losartan taken twice daily for up to 10 days.		Standard of Care
All Cause Mortality
	Group A (Study Drug+SOC)		Group B (SOC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/16 (6.3%)		1/15 (6.7%)
Serious Adverse Events
	Group A (Study Drug+SOC)		Group B (SOC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	Group A (Study Drug+SOC)		Group B (SOC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/16 (18.8%)		5/15 (33.3%)
General disorders
Body aches	1/16 (6.3%)	1	1/15 (6.7%)	1
Cough	0/16 (0%)	0	2/15 (13.3%)	2
Headache	0/16 (0%)	0	2/15 (13.3%)	2
Transaminitis	1/16 (6.3%)	1	1/15 (6.7%)	1
Malnutrition	0/16 (0%)	0	2/15 (13.3%)	2
Vascular disorders
Hypotension (SBP<100)	3/16 (18.8%)	3	4/15 (26.7%)	4

Limitations/Caveats

The generalizability is limited by small size of the study population, unblinded design, and all the subjects being screened from three hospitals in close proximity in one geographic area in Southern California.

More Information

Certain Agreements

Principal Investigators are NOT 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.