Study of Open Label Losartan in COVID-19

NCT ID: NCT04335123

Last Updated: 2024-08-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-04
• Study Completion Date: 2020-08-17

Brief Summary

This is an open label, phase 1 clinical trial to evaluate the safety of losartan in respiratory failure due to COVID-19.

Briefly, 34 patients with COVID-19 and respiratory failure who meet eligibility criteria and agree to participation in the study will be placed on losartan 25 mg daily on study day 0. If parameters are met the dose of losartan will be increased to 50 mg once daily on study day 3. Participants will continue losartan until they experience resolution of respiratory failure (normal oxygen levels on room air), are discharged from the hospital, meet stoppage criteria (detailed below) or complete 14 days of therapy.

Patients and/or surrogate decision maker who do not give consent to treatment will be asked to allow collection of data from their medical record for use as a control group. We will also collect medical information relating to safety criteria on historical controls treated at the University of Kansas Hospital in the 30 days prior to the study start date and during the study period.

Detailed Description

This is an open label, phase 1 clinical trial to evaluate the safety of losartan in respiratory failure due to COVID-19.

Clinical Trial setup:

Detailed inclusion and exclusion criteria are listed below. Briefly, 34 patients with COVID-19 and respiratory failure who meet criteria and agree to participation in the study will be placed on losartan 25 mg daily on study day 0. If parameters are met the dose of losartan will be increased to 50 mg once daily on study day 3. Participants will continue losartan until they experience resolution of respiratory failure (normal oxygen levels on room air), are discharged from the hospital, meet stoppage criteria (detailed below) or complete 14 days of therapy.

Patients and/or surrogate decision maker who do not give consent to treatment will be asked to allow collection of data from their medical record for use as a control group.

Stoppage criteria for losartan

• Hyperkalemia (persistent values >5.5 mM recorded on at least 2 readings).
• Worsening renal function (Cockcroft-Gault <30 mL/min/1.73 m2) or urinary output <20 mL/h.
• Skin rashes, palpitations or other moderate or severe adverse events (interference with usual daily activities) without clear explanation should warrant immediate cessation of treatment and notification of study personnel.
• Development of sustained hypotension defined as SBP <90 mmHg, DBP <60 mmHg recorded on at least two readings 30 min apart or use of norepinephrine >0.1 µg/kg/min.
• Any change in monitor lab parameters deemed significant and potentially related to study drug by the Investigator.

Conditions

COVID-19

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Open Label Losartan

50 patients with COVID-19 and respiratory failure who meet criteria and agree to participation in the study will be placed on losartan 25 mg once daily on study day 0. If parameters are met the dose of losartan will be increased to 50 mg once daily on study day 3. Participants will continue losartan until they experience resolution of respiratory failure (normal oxygen levels on room air), are discharged from the hospital, meet stoppage criteria or complete 14 days of therapy.

Group Type: EXPERIMENTAL

Losartan

Intervention Type: DRUG

25 mg QD from day 0 to day 3. Dose escalation to 50 mg QD until study completion

External Control

Matched - contemporaneous control who met enrollment criteria and were treated at UKHS during the COVID-19 pandemic period.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Losartan

25 mg QD from day 0 to day 3. Dose escalation to 50 mg QD until study completion

Intervention Type: DRUG

Other Intervention Names

Cozaar

Eligibility Criteria

Inclusion Criteria

• Age >18 years admitted to the University of Kansas Health System.
• Confirmation of infection with SARS-CoV-2 by PCR testing.
• Hypoxic respiratory failure Requiring mechanical ventilation or oxygen OR a SpO2 ≤94% on room air or a PaO2/FiO2 (P/F) ratio <300 OR tachypnea (respiratory rate ≥24 breaths/min). Criteria to be met within 48 hours prior to Day 0.
• Other concomitant medications such as antivirals and hydroxychloroquine are allowed.
• Participants prescribed standard of care (SOC) losartan (25mg QD) within 48 hours of consenting may be considered for enrollment if eligibility criteria are met based on EMR data assessment, i.e. no other ARB or ACE prior to SOC medication administration. If participant is eligible and signs consent form, investigational losartan 25mg QD will be ordered to replace SOC prescription on the following scheduled dose.

• Current chronic use of medication with known interactions with losartan including NSAIDs (intermittent prior use is acceptable), potassium supplementation aliskiren.
• Blood pressure less than 90 mm Hg systolic or 60 mm Hg diastolic recorded on at least two readings 30 min apart.
• Need for vasopressors, unless norepinephrine ≤0.1 µg/kg/min
• Hyperkalemia (serum K+ >5.5 mM).
• Known cardiac failure (left ventricular ejection fraction ≤35%), renal insufficiency (Cockcroft-Gault <30 mL/min/1.73 m2 or urinary output <20 mL/h), hepatic failure (LFTs > 5x normal upper limit).
• Known renal artery stenosis.
• Neurological, psychiatric, endocrine or neoplastic diseases that are judged to interfere with participation in the study.
• On another interventional trial (including one for COVID-19) that excludes participation.

Exclusion Criteria

• Pregnancy.
• Respiratory failure due to a process other than COVID-19.
• Intolerance to ARBs.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Kansas Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Matthias Salathe, MD

Professor- University of Kansas Medical Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Matthias Salathe

Role: PRINCIPAL_INVESTIGATOR

University of Kansas Medical Center

Locations

University of Kansas Medical Center

Kansas City, Kansas, United States

Countries

United States

References

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

Reference Type: DERIVED

PMID: 32658300 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

STUDY00145514

Identifier Type: -

Identifier Source: org_study_id