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

• ClinicalTrials.gov Identifier: NCT04340557
• Recruitment Status: Completed
• First Posted: April 9, 2020
• Results First Posted: May 26, 2021
• Last Update Posted: May 26, 2021
• Sponsor: Sharp HealthCare
• Information provided by (Responsible Party): Matthew Geriak, Sharp HealthCare

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 (Clinical Trial)
• 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.
• 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: March 27, 2020
• Actual Primary Completion Date: June 13, 2020
• Actual Study Completion Date: June 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 Name: Losartan + Standard of Care
No Intervention: Group B (SOC); Standard of Care

Outcome Measures

Primary Outcome Measures :

1. Mechanical Ventilation [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

United States, California

Sharp Grossmont Hospital

La Mesa, California, United States, 91942

Sharp Chula Vista Medical Center

San Diego, California, United States, 91911

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)

Documents provided by Matthew Geriak, Sharp HealthCare:

Study Protocol and Statistical Analysis Plan  [PDF] April 20, 2020

More Information

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

Geriak M, Haddad F, Kullar R, Greenwood KL, Habib M, Habib C, Willms D, Sakoulas G. Randomized Prospective Open Label Study Shows No Impact on Clinical Outcome of Adding Losartan to Hospitalized COVID-19 Patients with Mild Hypoxemia. Infect Dis Ther. 2021 Sep;10(3):1323-1330. doi: 10.1007/s40121-021-00453-3. Epub 2021 May 11.

• Responsible Party: Matthew Geriak, Investigational Pharmacist, Sharp HealthCare
• ClinicalTrials.gov Identifier: NCT04340557
• Other Study ID Numbers: COVID-ARB; 2003902 ( Other Identifier: Sharp HealthCare Institutional Review Board (SHC IRB) )
• First Posted: April 9, 2020
• Results First Posted: May 26, 2021
• Last Update Posted: May 26, 2021
• Last Verified: May 2021

Individual Participant Data (IPD) Sharing Statement:

• 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, Sharp HealthCare:

Coronavirus; Angiotensin receptor blocker; SARS-CoV-2; COVID-19

Additional relevant MeSH terms:

Infections; Communicable Diseases; COVID-19; Severe Acute Respiratory Syndrome; Disease Attributes; Pathologic Processes; Respiratory Tract Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Losartan; Anti-Arrhythmia Agents; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Molecular Mechanisms of Pharmacological Action