The first randomized controlled trial of an ARB for treatment of COVID-19 returned preliminary results showing possible improvements in time to discharge, need for supplementary oxygen and CRP . See "Telmisartan for treatment of Covid-19 patients: an open randomized clinical trial. Preliminary report. " See independent critical appraisal of trial.
List of Angiotensin-receptor blocker (ARB) trials for COVID-19:
Do Angiotensin Receptor Blockers Mitigate Progression to Acute Respiratory Distress Syndrome With SARS-CoV-2 Infection . Intervention : losartan 12.5mg bid, can be increased based on SBP.Valsartan for Prevention of Acute Respiratory Distress Syndrome in Hospitalized Patients With SARS-COV-2 (COVID-19) Infection Disease . Intervention : valsartan titrated based on BP, maximum of 160mg bid.COVID MED Trial - Comparison Of Therapeutics for Hospitalized Patients Infected With SARS-CoV-2 (COVIDMED) . Intervention : losartan, 25 mg po QD X 5-14 days "depending on availability."Study of Open Label Losartan in COVID-19 . Intervention : losartan 25mg qd, escalated to 50mg od.Losartan for Patients With COVID-19 Requiring Hospitalization . Intervention : losartan 50mg od.Losartan for Patients With COVID-19 Not Requiring Hospitalization . Intervention : losartan 25mg od.Telmisartan for Treatment of COVID-19 Patients . Intervention : Telmisartan 80mg bid.
Treatments to Decrease the Risk of Hospitalization or Death in Elderly Outpatients With Symptomatic SARS-CoV-2 Infection (COVID-19) (COVERAGE) . Intervention : telmisartan 20mg od.
Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 respIraTorY Disease (CLARITY) . Intervention : ARB, dose/medication not specified.CLARITY 2.0 . Intervention : ARB, dose/medication unknown, plus CCR2-inhibitor, DMX-200.Chloroquine + Losartan Compared to Chloroquine Alone for the Treatment of COVID-19 Pneumonia . Intervention : losartan 25mg bid.Early Treatment With Ivermectin and LosarTAN for Cancer Patients With COVID-19 Infection (TITAN) . Intervention : losartan 50mg od.Austrian CoronaVirus Adaptive Clinical Trial (COVID-19) (ACOVACT) . Intervention : candesartan 4mg od, titrated up based on BP.Pilot Clinical Trial of the Safety and Efficacy of Telmisartan for the Mitigation of Pulmonary and Cardiac Complications in COVID-19 Patients . Intervention : telmisartan 40mg od.Host Response Mediators in Coronavirus (COVID-19) Infection (ARBS CORONA I) . Intervention : observational study of existing ACEi/ARB users.
Host response mediators in Coronavirus (COVID-19) infection - Is there a protective effect of ARBs on outcomes of Coronavirus infection? (ARBs CORONA II) . Intervention : losartan 25mg, then 24 hours later 50mg, then 24 hours later 100mg.
The McGill RAAS-COVID-19 Randomized Controlled Trial (RAAS-COVID) . Intervention : observational study of existing ACEi/ARB users. Will suspend or hold ACEi/ARB.Telmisartan in Respiratory Failure Due to COVID-19 (STAR-COVID) . Intervention : telmisartan 40mg od.Evaluation of the effects of Losartan in patients with corona virus disease 2019 . Intervention : losartan 25mg bid.The COVID-RASi Trial (COVID-19) . Intervention : ACEi or ARB of choice (unspecified).Losartan and Spironolactone Treatment for ICU Patients With COVID-19 Suffering From ARDS (COVIDANCE) . Intervention : losartan 50mg od, Spironolactone 25mg od.Combination Therapies to Reduce Carriage of SARS-Cov-2 and Improve Outcome of COVID-19 in Ivory Coast: a Phase Randomized IIb Trial (INTENSE-COV) . Intervention : Lopinavir/ritonavir + telmisartan. Telmisartan 40mg od for 10 days.INvestigating TELmisartin Study (INTEL) . Intervention : telmisartan 80mg Using the blood pressure medication losartan to improve outcomes for patients with SARS CoV-2 . Intervention : losartan 25mg od or losartan 50mg od depending on systolic blood pressure at randomization.Safety, tolerability, and outcomes of losartan use in patients hospitalized with SARS-CoV-2 infection: A feasibility study . This was a prospective cohort study comparing de novo initiation of losartan in hospitalized hypertensive COVID-19 patients to a retrospective cohort of hospitalized hypertensive COVID-19 patients already on losartan. Intervention : losartan 25mg od, titrated daily by 25mg until 100mg od.
Results : "In this pilot study we demonstrate that losartan was well-tolerated among hospitalized patients with COVID-19 and hypertension...There were suggestions of lung protection with losartan use, including the observation of an improvement in S/F ratio during hospitalization in the prospective cohort, however these findings would need validation through a properly designed randomized clinical trial (RCT)"Paper : results paper in PLOS ONE .
Planned meta-analysis (Cochrane Reviews) . A Cochrane Reviews meta analysis of renin-angiotensin inhibitors for COVID-19 is planned .
Other trials of renin-angiotensin modulation for COVID-19:
C21, an AT2R agonist, has shown benefit in animal lung injury models, similar to ARBs. In a recent randomized, placebo-controlled clinical trial , C21 showed promise as COVID-19 treatment. Photo CC-BY Rathinasabapathy, et al .
While not a trial of ARBs as therapy, BRACE CORONA was a randomized controlled trial exploring stopping-versus-continuing ACE inhibitors/ARBs in patients with hypertension. It showed no harm in continuation of ACE inhibitors and ARBs with COVID-19. There was a non-statistically significant hint of a benefit in the ACEi/ARB group but the trial was not powered to detect this.
Treatment of Angiotensin Peptide (1-7) for COVID-19 Angiotensin-(1,7) Treatment in COVID-19: the ATCO Trial (ATCO) Angiotensin 1-7 in the Therapy of Covid19 TXA COVID-19 Clinical Trial Angiotensin (1-7) for the Treatment of COVID-19 in Hospitalized Patients Recombinant Human Angiotensin-converting Enzyme 2 (rhACE2) as a Treatment for Patients With COVID-19 (APN01-COVID-19) Testing the Efficacy and Safety of BIO101 for the Prevention of Respiratory Deterioration in COVID-19 Patients (COVA)
RAS and Coagulopathy in COVID19 . Trial of AT1R agonist TRV027.Safety and Efficacy of C21 in Subjects With COVID-19 . Intervention : AT2R agonist C21, 100mg bid.
Results : "14 of 51 patients (27%) on a twice-daily dose of the drug (n=51) plus standard of care required oxygen therapy at the end of the treatment period vs. 22 of 55 patients (45%) in the control arm. That corresponds to a 40% relative risk reduction, an effect, the company said, that was “statistically significant (p=0.057) at the 10% level as predefined in the statistical analysis plan." - Press release on C21 results .Updated results : "At the end of the trial, about a week after the last dose of C21, the effect was even more pronounced, with only one patient in the C21 group still needing oxygen supplementation compared to 11 patients in the placebo group - a reduction by >90% (p<0.002)." - Press release on updated C21 results .
REPLACE COVID was an open-label trial of continuation versus discontinuation of renin–angiotensin system inhibitors in hospialized COVID-19 patients . Building on the results of BRACE CORONA, it found: "Continuation of ACEI or ARB therapy among patients admitted to hospital with COVID-19 had no overall effect on severity of COVID-19 disease course." According to trial investigator Jordana B Cohen, MD , "consistent with society recommendations considering the observational evidence, our findings support that ACEIs & ARBs can be safely continued in patients who are hospitalized with COVID-19. Ongoing studies are evaluating if de novo introduction of ARBs is helpful to treat COVID-19."
See also
The first randomized controlled trial of an ARB for treatment of COVID-19 returned preliminary results showing possible improvements in time to discharge, need for supplementary oxygen and CRP . See "Telmisartan for treatment of Covid-19 patients: an open randomized clinical trial. Preliminary report. " See independent critical appraisal of trial.
List of Angiotensin-receptor blocker (ARB) trials for COVID-19:
Do Angiotensin Receptor Blockers Mitigate Progression to Acute Respiratory Distress Syndrome With SARS-CoV-2 Infection . Intervention : losartan 12.5mg bid, can be increased based on SBP.Valsartan for Prevention of Acute Respiratory Distress Syndrome in Hospitalized Patients With SARS-COV-2 (COVID-19) Infection Disease . Intervention : valsartan titrated based on BP, maximum of 160mg bid.COVID MED Trial - Comparison Of Therapeutics for Hospitalized Patients Infected With SARS-CoV-2 (COVIDMED) . Intervention : losartan, 25 mg po QD X 5-14 days "depending on availability."Study of Open Label Losartan in COVID-19 . Intervention : losartan 25mg qd, escalated to 50mg od.Losartan for Patients With COVID-19 Requiring Hospitalization . Intervention : losartan 50mg od.Losartan for Patients With COVID-19 Not Requiring Hospitalization . Intervention : losartan 25mg od.Telmisartan for Treatment of COVID-19 Patients . Intervention : Telmisartan 80mg bid.
Treatments to Decrease the Risk of Hospitalization or Death in Elderly Outpatients With Symptomatic SARS-CoV-2 Infection (COVID-19) (COVERAGE) . Intervention : telmisartan 20mg od.
Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 respIraTorY Disease (CLARITY) . Intervention : ARB, dose/medication not specified.CLARITY 2.0 . Intervention : ARB, dose/medication unknown, plus CCR2-inhibitor, DMX-200.Chloroquine + Losartan Compared to Chloroquine Alone for the Treatment of COVID-19 Pneumonia . Intervention : losartan 25mg bid.Early Treatment With Ivermectin and LosarTAN for Cancer Patients With COVID-19 Infection (TITAN) . Intervention : losartan 50mg od.Austrian CoronaVirus Adaptive Clinical Trial (COVID-19) (ACOVACT) . Intervention : candesartan 4mg od, titrated up based on BP.Pilot Clinical Trial of the Safety and Efficacy of Telmisartan for the Mitigation of Pulmonary and Cardiac Complications in COVID-19 Patients . Intervention : telmisartan 40mg od.Host Response Mediators in Coronavirus (COVID-19) Infection (ARBS CORONA I) . Intervention : observational study of existing ACEi/ARB users.
Host response mediators in Coronavirus (COVID-19) infection - Is there a protective effect of ARBs on outcomes of Coronavirus infection? (ARBs CORONA II) . Intervention : losartan 25mg, then 24 hours later 50mg, then 24 hours later 100mg.
The McGill RAAS-COVID-19 Randomized Controlled Trial (RAAS-COVID) . Intervention : observational study of existing ACEi/ARB users. Will suspend or hold ACEi/ARB.Telmisartan in Respiratory Failure Due to COVID-19 (STAR-COVID) . Intervention : telmisartan 40mg od.Evaluation of the effects of Losartan in patients with corona virus disease 2019 . Intervention : losartan 25mg bid.The COVID-RASi Trial (COVID-19) . Intervention : ACEi or ARB of choice (unspecified).Losartan and Spironolactone Treatment for ICU Patients With COVID-19 Suffering From ARDS (COVIDANCE) . Intervention : losartan 50mg od, Spironolactone 25mg od.Combination Therapies to Reduce Carriage of SARS-Cov-2 and Improve Outcome of COVID-19 in Ivory Coast: a Phase Randomized IIb Trial (INTENSE-COV) . Intervention : Lopinavir/ritonavir + telmisartan. Telmisartan 40mg od for 10 days.INvestigating TELmisartin Study (INTEL) . Intervention : telmisartan 80mg Using the blood pressure medication losartan to improve outcomes for patients with SARS CoV-2 . Intervention : losartan 25mg od or losartan 50mg od depending on systolic blood pressure at randomization.Safety, tolerability, and outcomes of losartan use in patients hospitalized with SARS-CoV-2 infection: A feasibility study . This was a prospective cohort study comparing de novo initiation of losartan in hospitalized hypertensive COVID-19 patients to a retrospective cohort of hospitalized hypertensive COVID-19 patients already on losartan. Intervention : losartan 25mg od, titrated daily by 25mg until 100mg od.
Results : "In this pilot study we demonstrate that losartan was well-tolerated among hospitalized patients with COVID-19 and hypertension...There were suggestions of lung protection with losartan use, including the observation of an improvement in S/F ratio during hospitalization in the prospective cohort, however these findings would need validation through a properly designed randomized clinical trial (RCT)"Paper : results paper in PLOS ONE .
Planned meta-analysis (Cochrane Reviews) . A Cochrane Reviews meta analysis of renin-angiotensin inhibitors for COVID-19 is planned .
While not a trial of ARBs as therapy, BRACE CORONA was a randomized controlled trial exploring stopping-versus-continuing ACE inhibitors/ARBs in patients with hypertension. It showed no harm in continuation of ACE inhibitors and ARBs with COVID-19. There was a non-statistically significant hint of a benefit in the ACEi/ARB group but the trial was not powered to detect this.
Other trials of renin-angiotensin modulation for COVID-19:
In a double-blind, randomized, placebo-controlled trial, AT2R agonist C21 , one patient in the C21 group required supplementary oxygen at day 14 versus 11 patients in the placebo group (p=0.003).
C21, an AT2R agonist, has shown benefit in animal lung injury models, similar to ARBs. In a recent randomized, placebo-controlled clinical trial , C21 showed promise as COVID-19 treatment. Photo CC-BY Rathinasabapathy, et al .
Treatment of Angiotensin Peptide (1-7) for COVID-19 Angiotensin-(1,7) Treatment in COVID-19: the ATCO Trial (ATCO) Angiotensin 1-7 in the Therapy of Covid19 TXA COVID-19 Clinical Trial Angiotensin (1-7) for the Treatment of COVID-19 in Hospitalized Patients Recombinant Human Angiotensin-converting Enzyme 2 (rhACE2) as a Treatment for Patients With COVID-19 (APN01-COVID-19) Testing the Efficacy and Safety of BIO101 for the Prevention of Respiratory Deterioration in COVID-19 Patients (COVA)
RAS and Coagulopathy in COVID19 . Trial of AT1R agonist TRV027.Safety and Efficacy of C21 in Subjects With COVID-19 . Intervention : AT2R agonist C21, 100mg bid.
Results : 106 patients underwent randomization (51 in the C21 group and 55 in the placebo group). At day 14 after start of treatment, the proportion of patients still requiring supplemental oxygen was significantly reduced by 90% in the C21 group compared to the placebo group (p=0.003). Moreover, fewer patients required mechanical ventilation (one C21 patient and four placebo patients), and C21 was associated with a numerical reduction in the mortality rate (one and three deaths in the C21 and placebo group, respectively). Treatment with C21 was safe and well tolerated.Trial results preprint.
REPLACE COVID was an open-label trial of continuation versus discontinuation of renin–angiotensin system inhibitors in hospialized COVID-19 patients . Building on the results of BRACE CORONA, it found: "Continuation of ACEI or ARB therapy among patients admitted to hospital with COVID-19 had no overall effect on severity of COVID-19 disease course." According to trial investigator Jordana B Cohen, MD , "consistent with society recommendations considering the observational evidence, our findings support that ACEIs & ARBs can be safely continued in patients who are hospitalized with COVID-19. Ongoing studies are evaluating if de novo introduction of ARBs is helpful to treat COVID-19."
See also
philipn authored on Jan. 28, 2021, 10:17 a.m. 
