Trial Outcomes & Findings for Study of Open Label Losartan in COVID-19 (NCT NCT04335123)

NCT ID: NCT04335123

Last Updated: 2024-08-02

Results Overview

Safety will be reported based on Protocol defined AEs. For the purpose of this protocol, an AE will be defined as as any untoward medical occurrence in a subject during the study listed under DMSB - Anticipated Adverse Events and Grading Scale section of this protocol as well as safety monitoring data listed on protocol table 1 as well as stoppage criteria for losartan. The event does not necessarily have a causal relationship with the treatment. AEs will be collected for both study groups, treatment and control from the time the ICF is signed until the subject completes study participation.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 34 participants
• Primary outcome timeframe: 14 days of losartan treatment
• Results posted on: 2024-08-02

Participant Flow

External control group were hospitalized during study period and met enrollment criteria and were not enrolled. Participants were matched to losartan group on baseline characteristics.

Participant milestones

Measure	Open Label Losartan 34 patients with COVID-19 and respiratory failure participated in the study and were placed on losartan 25 mg once daily on study day 0. Losartan dose was increased to 50 mg once daily on study day 3. Participants continued losartan until they experienced resolution of respiratory failure (normal oxygen levels on room air), were discharged from the hospital, met stoppage criteria or completed 14 days of therapy. Losartan: 25 mg QD from day 0 to day 3. Dose escalation to 50 mg QD until study completion	External Control A group of external controls matched to the enrolled participants
Overall Study STARTED	34	46
Overall Study COMPLETED	30	46
Overall Study NOT COMPLETED	4	0

Reasons for withdrawal

Measure	Open Label Losartan 34 patients with COVID-19 and respiratory failure participated in the study and were placed on losartan 25 mg once daily on study day 0. Losartan dose was increased to 50 mg once daily on study day 3. Participants continued losartan until they experienced resolution of respiratory failure (normal oxygen levels on room air), were discharged from the hospital, met stoppage criteria or completed 14 days of therapy. Losartan: 25 mg QD from day 0 to day 3. Dose escalation to 50 mg QD until study completion	External Control A group of external controls matched to the enrolled participants
Overall Study Withdrawal by Subject	2	0
Overall Study Physician Decision	2	0

Baseline Characteristics

Study of Open Label Losartan in COVID-19

Baseline characteristics by cohort

Measure	Open Label Losartan n=30 Participants 34 patients with COVID-19 and respiratory failure participated in the study and were placed on losartan 25 mg once daily on study day 0. Losartan dose was increased to 50 mg once daily on study day 3. Participants continued losartan until they experienced resolution of respiratory failure (normal oxygen levels on room air), were discharged from the hospital, met stoppage criteria or completed 14 days of therapy. Losartan: 25 mg QD from day 0 to day 3. Dose escalation to 50 mg QD until study completion	External Controls n=46 Participants 46 external controls matched to losartan participants upon baseline characteristics.	Total n=76 Participants Total of all reporting groups
Age, Continuous	54.2 years STANDARD_DEVIATION 15.1 • n=5 Participants	53.8 years STANDARD_DEVIATION 15.5 • n=7 Participants	54 years STANDARD_DEVIATION 15.3 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	21 Participants n=7 Participants	34 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	25 Participants n=7 Participants	42 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants	21 Participants n=7 Participants	29 Participants n=5 Participants
Race (NIH/OMB) White	15 Participants n=5 Participants	11 Participants n=7 Participants	26 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	7 Participants n=5 Participants	12 Participants n=7 Participants	19 Participants n=5 Participants

PRIMARY outcome

Timeframe: 14 days of losartan treatment

Safety will be reported based on Protocol defined AEs.

For the purpose of this protocol, an AE will be defined as as any untoward medical occurrence in a subject during the study listed under DMSB - Anticipated Adverse Events and Grading Scale section of this protocol as well as safety monitoring data listed on protocol table 1 as well as stoppage criteria for losartan.

The event does not necessarily have a causal relationship with the treatment. AEs will be collected for both study groups, treatment and control from the time the ICF is signed until the subject completes study participation.

Outcome measures

Measure	Open Label Losartan n=30 Participants 34 patients with COVID-19 and respiratory failure participated in the study and were placed on losartan 25 mg once daily on study day 0. Losartan dose was increased to 50 mg once daily on study day 3. Participants continued losartan until they experienced resolution of respiratory failure (normal oxygen levels on room air), were discharged from the hospital, met stoppage criteria or completed 14 days of therapy. Losartan: 25 mg QD from day 0 to day 3. Dose escalation to 50 mg QD until study completion	External Controls n=46 Participants 46 external controls matched to losartan participants upon baseline characteristics.
Number of Participants With Treatment-related Adverse Events as Assessed by Protocol Definition of AE	24 Participants	44 Participants

SECONDARY outcome

Timeframe: 14 days of losartan treatment

Number of days on supplemental oxygen in respiratory failure due to COVID-19

Outcome measures

Measure	Open Label Losartan n=30 Participants 34 patients with COVID-19 and respiratory failure participated in the study and were placed on losartan 25 mg once daily on study day 0. Losartan dose was increased to 50 mg once daily on study day 3. Participants continued losartan until they experienced resolution of respiratory failure (normal oxygen levels on room air), were discharged from the hospital, met stoppage criteria or completed 14 days of therapy. Losartan: 25 mg QD from day 0 to day 3. Dose escalation to 50 mg QD until study completion	External Controls n=46 Participants 46 external controls matched to losartan participants upon baseline characteristics.
Number of Days on Supplemental Oxygen in Respiratory Failure Due to COVID-19	4 days Interval 2.0 to 6.0	4 days Interval 0.0 to 9.0

SECONDARY outcome

Timeframe: 14 days of losartan treatment

Number of participants with mechanical ventilation use

Outcome measures

Measure	Open Label Losartan n=30 Participants 34 patients with COVID-19 and respiratory failure participated in the study and were placed on losartan 25 mg once daily on study day 0. Losartan dose was increased to 50 mg once daily on study day 3. Participants continued losartan until they experienced resolution of respiratory failure (normal oxygen levels on room air), were discharged from the hospital, met stoppage criteria or completed 14 days of therapy. Losartan: 25 mg QD from day 0 to day 3. Dose escalation to 50 mg QD until study completion	External Controls n=46 Participants 46 external controls matched to losartan participants upon baseline characteristics.
Number of Participants With Mechanical Ventilation Use	2 Participants	9 Participants

SECONDARY outcome

Timeframe: 14 days of losartan treatment

Days on mechanical ventilation

Outcome measures

Measure	Open Label Losartan n=30 Participants 34 patients with COVID-19 and respiratory failure participated in the study and were placed on losartan 25 mg once daily on study day 0. Losartan dose was increased to 50 mg once daily on study day 3. Participants continued losartan until they experienced resolution of respiratory failure (normal oxygen levels on room air), were discharged from the hospital, met stoppage criteria or completed 14 days of therapy. Losartan: 25 mg QD from day 0 to day 3. Dose escalation to 50 mg QD until study completion	External Controls n=46 Participants 46 external controls matched to losartan participants upon baseline characteristics.
Days on Mechanical Ventilation	0 days Interval 0.0 to 0.0	11 days Interval 8.0 to 14.0

SECONDARY outcome

Timeframe: 14 days of losartan treatment

Number of participants with non-invasive positive pressure ventilation or heated high flow nasal cannula use

Outcome measures

Measure	Open Label Losartan n=30 Participants 34 patients with COVID-19 and respiratory failure participated in the study and were placed on losartan 25 mg once daily on study day 0. Losartan dose was increased to 50 mg once daily on study day 3. Participants continued losartan until they experienced resolution of respiratory failure (normal oxygen levels on room air), were discharged from the hospital, met stoppage criteria or completed 14 days of therapy. Losartan: 25 mg QD from day 0 to day 3. Dose escalation to 50 mg QD until study completion	External Controls n=46 Participants 46 external controls matched to losartan participants upon baseline characteristics.
Number of Participants With Non-invasive Positive Pressure Ventilation or Heated High Flow Nasal Cannula Use	6 Participants	3 Participants

SECONDARY outcome

Timeframe: 14 days of losartan treatment

Days on non-invasive positive pressure ventilation or high flow nasal cannula

Outcome measures

Measure	Open Label Losartan n=30 Participants 34 patients with COVID-19 and respiratory failure participated in the study and were placed on losartan 25 mg once daily on study day 0. Losartan dose was increased to 50 mg once daily on study day 3. Participants continued losartan until they experienced resolution of respiratory failure (normal oxygen levels on room air), were discharged from the hospital, met stoppage criteria or completed 14 days of therapy. Losartan: 25 mg QD from day 0 to day 3. Dose escalation to 50 mg QD until study completion	External Controls n=46 Participants 46 external controls matched to losartan participants upon baseline characteristics.
Days on Non-invasive Positive Pressure Ventilation or High Flow Nasal Cannula	0 days Interval 0.0 to 0.0	5 days Interval 3.5 to 7.5

SECONDARY outcome

Timeframe: 14 days of losartan treatment

Population: Data regarding transfer to ICU was not collected for any participants during study period and thus not reported.

Number of participants with transfer to ICU from non-ICU hospital bed

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 14 days of losartan treatment

ICU length of stay (days)

Outcome measures

Measure	Open Label Losartan n=30 Participants 34 patients with COVID-19 and respiratory failure participated in the study and were placed on losartan 25 mg once daily on study day 0. Losartan dose was increased to 50 mg once daily on study day 3. Participants continued losartan until they experienced resolution of respiratory failure (normal oxygen levels on room air), were discharged from the hospital, met stoppage criteria or completed 14 days of therapy. Losartan: 25 mg QD from day 0 to day 3. Dose escalation to 50 mg QD until study completion	External Controls n=46 Participants 46 external controls matched to losartan participants upon baseline characteristics.
ICU Length of Stay (Days)	0 days Interval 0.0 to 11.5	10 days Interval 7.5 to 13.5

SECONDARY outcome

Timeframe: 14 days after study enrollment

in hospital mortality rate

Outcome measures

Measure	Open Label Losartan n=30 Participants 34 patients with COVID-19 and respiratory failure participated in the study and were placed on losartan 25 mg once daily on study day 0. Losartan dose was increased to 50 mg once daily on study day 3. Participants continued losartan until they experienced resolution of respiratory failure (normal oxygen levels on room air), were discharged from the hospital, met stoppage criteria or completed 14 days of therapy. Losartan: 25 mg QD from day 0 to day 3. Dose escalation to 50 mg QD until study completion	External Controls n=46 Participants 46 external controls matched to losartan participants upon baseline characteristics.
in Hospital Mortality Rate	1 Participants	3 Participants

SECONDARY outcome

Timeframe: from enrollment through hospital discharge

Hospital length of stay (days)

Outcome measures

Measure	Open Label Losartan n=30 Participants 34 patients with COVID-19 and respiratory failure participated in the study and were placed on losartan 25 mg once daily on study day 0. Losartan dose was increased to 50 mg once daily on study day 3. Participants continued losartan until they experienced resolution of respiratory failure (normal oxygen levels on room air), were discharged from the hospital, met stoppage criteria or completed 14 days of therapy. Losartan: 25 mg QD from day 0 to day 3. Dose escalation to 50 mg QD until study completion	External Controls n=46 Participants 46 external controls matched to losartan participants upon baseline characteristics.
Hospital Length of Stay (Days)	9 days Interval 6.0 to 14.75	7 days Interval 4.0 to 13.5

SECONDARY outcome

Timeframe: 14 days of losartan treatment

Cumulative number of participants with severe adverse events

Outcome measures

Measure	Open Label Losartan n=30 Participants 34 patients with COVID-19 and respiratory failure participated in the study and were placed on losartan 25 mg once daily on study day 0. Losartan dose was increased to 50 mg once daily on study day 3. Participants continued losartan until they experienced resolution of respiratory failure (normal oxygen levels on room air), were discharged from the hospital, met stoppage criteria or completed 14 days of therapy. Losartan: 25 mg QD from day 0 to day 3. Dose escalation to 50 mg QD until study completion	External Controls n=46 Participants 46 external controls matched to losartan participants upon baseline characteristics.
Cumulative Number of Participants With of Severe Adverse Events	0 participants	0 participants

SECONDARY outcome

Timeframe: 14 days of losartan treatment

Number of participants with increase in supplemental oxygen needs from baseline.

Outcome measures

Measure	Open Label Losartan n=30 Participants 34 patients with COVID-19 and respiratory failure participated in the study and were placed on losartan 25 mg once daily on study day 0. Losartan dose was increased to 50 mg once daily on study day 3. Participants continued losartan until they experienced resolution of respiratory failure (normal oxygen levels on room air), were discharged from the hospital, met stoppage criteria or completed 14 days of therapy. Losartan: 25 mg QD from day 0 to day 3. Dose escalation to 50 mg QD until study completion	External Controls n=46 Participants 46 external controls matched to losartan participants upon baseline characteristics.
Number of Participants With Increase of Supplemental Oxygen Needs From Baseline.	4 Participants	12 Participants

SECONDARY outcome

Timeframe: 14 days of losartan treatment

Number of participants with medications with possible antiviral activity (hydroxychloroquine, lopinavir/ritonavir, ribavirin or remdesivir) or adjunctive therapy use (e.g., tocilizumab)

Outcome measures

Measure	Open Label Losartan n=30 Participants 34 patients with COVID-19 and respiratory failure participated in the study and were placed on losartan 25 mg once daily on study day 0. Losartan dose was increased to 50 mg once daily on study day 3. Participants continued losartan until they experienced resolution of respiratory failure (normal oxygen levels on room air), were discharged from the hospital, met stoppage criteria or completed 14 days of therapy. Losartan: 25 mg QD from day 0 to day 3. Dose escalation to 50 mg QD until study completion	External Controls n=46 Participants 46 external controls matched to losartan participants upon baseline characteristics.
Number of Participants With Medications With Possible Antiviral Activity (Hydroxychloroquine, Lopinavir/Ritonavir, Ribavirin or Remdesivir) or Adjunctive Therapy Use (e.g., Tocilizumab)	30 Participants	30 Participants

SECONDARY outcome

Timeframe: 14 days of losartan treatment

Number of participants with extracorporeal membrane oxygenation use

Outcome measures

Measure	Open Label Losartan n=30 Participants 34 patients with COVID-19 and respiratory failure participated in the study and were placed on losartan 25 mg once daily on study day 0. Losartan dose was increased to 50 mg once daily on study day 3. Participants continued losartan until they experienced resolution of respiratory failure (normal oxygen levels on room air), were discharged from the hospital, met stoppage criteria or completed 14 days of therapy. Losartan: 25 mg QD from day 0 to day 3. Dose escalation to 50 mg QD until study completion	External Controls n=46 Participants 46 external controls matched to losartan participants upon baseline characteristics.
Number of Participants With Extracorporeal Membrane Oxygenation Use	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 14 days of losartan treatment

Population: This outcome was not collected for study participants, thus results are not reported

Number of participants with renal replacement therapy use

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 14 days of losartan treatment

Number of participants with intolerance to high dose (50mg) losartan after tolerating 25mg

Outcome measures

Measure	Open Label Losartan n=30 Participants 34 patients with COVID-19 and respiratory failure participated in the study and were placed on losartan 25 mg once daily on study day 0. Losartan dose was increased to 50 mg once daily on study day 3. Participants continued losartan until they experienced resolution of respiratory failure (normal oxygen levels on room air), were discharged from the hospital, met stoppage criteria or completed 14 days of therapy. Losartan: 25 mg QD from day 0 to day 3. Dose escalation to 50 mg QD until study completion	External Controls n=46 Participants 46 external controls matched to losartan participants upon baseline characteristics.
Number of Participants With Intolerance to High Dose (50mg) Losartan After Tolerating 25mg	2 Participants	0 Participants

Adverse Events

Open Label Losartan

Serious events: 0 serious events

Other events: 24 other events

Deaths: 1 deaths

External Controls

Serious events: 0 serious events

Other events: 44 other events

Deaths: 3 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Open Label Losartan n=30 participants at risk 34 patients with COVID-19 and respiratory failure participated in the study and were placed on losartan 25 mg once daily on study day 0. Losartan dose was increased to 50 mg once daily on study day 3. Participants continued losartan until they experienced resolution of respiratory failure (normal oxygen levels on room air), were discharged from the hospital, met stoppage criteria or completed 14 days of therapy. Losartan: 25 mg QD from day 0 to day 3. Dose escalation to 50 mg QD until study completion	External Controls n=46 participants at risk 46 external controls matched to losartan participants upon baseline characteristics.
Blood and lymphatic system disorders Low hemoglobin	50.0% 15/30 • Number of events 15 • From enrollment to hospital discharge, up to day 14.	69.6% 32/46 • Number of events 32 • From enrollment to hospital discharge, up to day 14.
Hepatobiliary disorders Elevated AST	36.7% 11/30 • Number of events 11 • From enrollment to hospital discharge, up to day 14.	65.2% 30/46 • Number of events 30 • From enrollment to hospital discharge, up to day 14.
Hepatobiliary disorders Elevated ALT	40.0% 12/30 • Number of events 12 • From enrollment to hospital discharge, up to day 14.	50.0% 23/46 • Number of events 23 • From enrollment to hospital discharge, up to day 14.
Renal and urinary disorders Elevated creatinine	30.0% 9/30 • Number of events 9 • From enrollment to hospital discharge, up to day 14.	26.1% 12/46 • Number of events 12 • From enrollment to hospital discharge, up to day 14.
Vascular disorders hypotension	26.7% 8/30 • Number of events 8 • From enrollment to hospital discharge, up to day 14.	30.4% 14/46 • Number of events 14 • From enrollment to hospital discharge, up to day 14.
Hepatobiliary disorders Elevated Alkaline phosphatase	16.7% 5/30 • Number of events 5 • From enrollment to hospital discharge, up to day 14.	30.4% 14/46 • Number of events 14 • From enrollment to hospital discharge, up to day 14.
Renal and urinary disorders Elevated potassium	10.0% 3/30 • Number of events 3 • From enrollment to hospital discharge, up to day 14.	30.4% 14/46 • Number of events 14 • From enrollment to hospital discharge, up to day 14.
Blood and lymphatic system disorders Leukopenia	6.7% 2/30 • Number of events 2 • From enrollment to hospital discharge, up to day 14.	30.4% 14/46 • Number of events 14 • From enrollment to hospital discharge, up to day 14.
Blood and lymphatic system disorders Low platelets	3.3% 1/30 • Number of events 1 • From enrollment to hospital discharge, up to day 14.	26.1% 12/46 • Number of events 12 • From enrollment to hospital discharge, up to day 14.

Additional Information

Dr Matthias Salathe

Kansas University Medical Center

Phone: 9135886000

Email: msalathe@kumc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place