None listed
Conditions
Brief summary
There are many current health and social needs in the COVID pandemic. From both a health and and economic perspective, the best population policy is to vaccinate. However, in the absence of a vaccine, a combination of minimizing exposure and using proven therapies to prevent flulike symptoms becoming lung failure requiring ventilation and ICU beds is the only strategy. The key to respiratory illness is the viral attack on the pulmonary Renin Angiotensin System (RAS), which drives a substantial inflammatory process. This has reached a zenith with SARS-CoV-2, which comprehensively dysregulates the pulmonary RAS processes by targeting a vital RAS component, the angiotensin-converting enzyme 2 (ACE2). It is this enzyme that becomes the molecular target or receptor for SARS-CoV-2 (COVID) infection with the concurrent loss of its role in physiologically countering RAS induced inflammation. We aim to study in an open label randomised trial the safety of a range of identifed, currently used ARB and ACEI's. The first compound selected is Losartan, a drug that interferes with the renin angiotensin system. Many retrospective studies have now reported significant mortality benefits for patients who are on RAS drugs when admitted to hospital. We aim to undertake a prospective study in patients not usually on such drugs to describe the safety, tolerability and efficacy of adding Losartan to the treatment regime in Australian hospitalised COVID patients
Interventions
This is a multisite, 3 stage inpatient study of the Angiotensin II Receptor Blocker Losartan for treatment of COVID-19. The three stages will be recruited sequentially.
In the first stage, 9 participants will be allocated to the active treatment. The first intervention studied will be Losartan 25mg tablet once daily, for 7 days, or their entire admission (whichever is longer).
Following complete recruitment to the first stage, participants will be allocated to the second stage of the study. I
This is a multisite, 3 stage inpatient study of the Angiotensin II Receptor Blocker Losartan for treatment of COVID-19. The three stages will be recruited sequentially. In the first stage, 9 participants will be allocated to the active treatment. The first intervention studied will be Losartan 25mg tablet once daily, for 7 days, or their entire admission (whichever is longer). Following complete recruitment to the first stage, participants will be allocated to the second stage of the study. In the second stage, 9 participants will start at 25mg Losartan. If hemodynamically stable after 24 hours, they will increase dose to 25mg twice daily for 7 days, or their entire admission (whichever is longer). If not (clinical decision) the participant will stay on 25mg daily for 7 days, or the remainder of for their admission (whichever is longer). Following complete recruitment to the first and second stages, participants will be allocated to the third stage of the study. In the third stage, 9 participants will start on 25 mg Losartan daily. If hemodynamically stable after 24 hours, they will increase dose to 25mg twice daily. Then, if hemodynamically stable after further 24 hours, they will increase dose again to 25mg morning and 50mg night. After a further 24 hours, and if the participant is hemodynamically stable, they will increase dose to 50mg twice daily for 7 days, or the remainder of for their admission (whichever is longer). For all stages, the dose will be held if the blood pressure systolic reading is less than 100mmHg, and/or a renal function decrease of greater than 30% from baseline is observed, or serum potassium greater than permitted by the institutional upper limit of normal (ULN) occurs. Losartan will be restarted at the previous dose level (or 25 mg if Stage 1) if resolution of the symptoms which caused the dose to be held, i.e. the Patient no longer has a blood pressure systolic reading less than 100mmHg, and/or a renal function decrease of greater than 30% from baseline, or serum potassium greater than permitted by the institutional ULN, is seen within 24 hours (when the next dose of drug due) for 7 days, or the remainder of their entire admission (whichever is longer). If not resolved, drug will not be reinstated and the participant will be withdrawn. Adherence to this treatment plan will be monitored by checking the administered interventions and observations recorded in patient medical records. Participants will also cease Losartan if they develop of any new grade 4 AE, not present at baseline, possibly or probably attributable to Losartan.
Sponsors
NSW Health via the Hunter New England Local Health District
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Confirmed SARS-CoV-2 infection by any method Current admission as inpatient to hospital ward for management of COVID-19
Exclusion criteria
Current use of RAS agent Known contra-indication to any RAS agent Participation in another clinical trial for COVID-19 or SARS-CoV-2 Current or previous admission to ICU for COVID-19 management
Outcome results
None listed