Results: "Of 432 screened patients, 14 were enrolled (3.5%), 9 received losartan and 5 combined control..Treatment with losartan was not associated with a difference in NCOSS slope of change in comparison with combined control (p=0.4) or placebo-only control (p=0.05) (trend favoring placebo). 60-day mortality and overall AE and SAE rates were numerically but not significantly higher with losartan."
Results: "On losartan, 24/30 (80%) experienced an adverse event as opposed to 29/30 (97%) of controls, with a lower average number of adverse events on losartan relative to control (2.2 vs 3.3). Using Poisson regression and controlling for age, sex, race, date of enrollment, disease severity at enrollment, and history of high-risk comorbidities, the incidence rate ratio of adverse events on losartan relative to control was 0.69 (95% CI: 0.49 - 0.97)
Conclusions: Losartan appeared safe for COVID-19-related acute respiratory compromise. To assess true efficacy, randomized trials are needed."
Results: "From April 2020 - February 2021, 205 participants were randomized, 101 to losartan and 104 to placebo. Compared to placebo, losartan did not significantly affect PaO2/FiO2 ratio at 7 days [difference of -24.8 (95% -55.6 to 6.1; p=0.12)]."
Results: From April-November 2020, 117 participants were randomized 58 to losartan and 59 to placebo. The primary outcome did not differ significantly between the two arms based on Barnard’s test [losartan arm: 3 events (5.2%; 95% CI 1.8-14.1%) versus placebo arm: 1 event(1.7% 95% CI 0.01-9.0%); proportion difference -3.5% (95% CI -12.7-4.5%); p=0.32]. Functional status, self-reported dyspnea, maximum daily temperatures, and viral load were not significantly different between treatment groups. Due to a lower than expected hospitalization rate and low likelihood of a clinically important treatment effect, the trial was terminated early.
Results: "..Day 5 control-group CRP levels were 6.06 ± 6.95 mg/dL (95% CI 7.79–4.35, n = 66) while telmisartan group were 3.83 ± 5.08 mg/dL (95% CI 5.08–2.59, n = 66, p = 0.038). Day 8 CRP levels were 6.30 ± 8.19 mg/dL (95% CI 8.79–3.81, n = 44) and 2.37 ± 3.47 mg/dL (95% CI 3.44–1.30, n = 43, p = 0.0098) in the control and telmisartan groups, respectively (all values expressed as mean ± SD). Kaplan-Meier analysis showed that telmisartan-treated patients had a lower median time-to-discharge (control=15 days; telmisartan=9 days). Death by day 30 was reduced in the telmisartan-treated group (control 22.54%, 16/71; telmisartan 4.29%, 3/70 participants; p = 0.0023). Composite ICU, mechanical ventilation or death was reduced by telmisartan treatment at days 15 and 30." -- Results paper.
Results: No statistically significant difference in the primary or secondary outcomes between the groups were seen. The small trial may have been unpowered to detect benefits of losartan, as there appeared to be non-statistically significant improvements in the losartan group. Additionally, as noted by the authors, in an observational study, amlodipine was associated with improved outcomes in COVID-19.
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)"
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.
"The primary endpoint of the trial was a composite endpoint of all-cause death or invasive mechanical ventilation up to 28 days or until hospital discharge. The data showed that fewer patients treated with APN01 (n=9) died or received invasive ventilation compared to placebo (n=12), although statistical significance was not achieved due to the low total number of events. Standard of care has improved dramatically since study initiation, resulting in fewer deaths and less use of nvasive mechanical ventilation than at the time of design of the study.
Secondary objectives included mechanical ventilator-free days, change in viral RNA load, improvements according to the WHO 11-Point score system and the evaluation of relevant biomarker changes following treatment with APN01. Treatment with APN01 was safe and well tolerated and no drug-related severe adverse events were observed during the study. The data demonstrated a statistically significant improvement in mechanical ventilator-free days in alive patients and reduction in viral load in the group treated with APN01 compared to placebo. APN01 also demonstrated a positive impact on key biomarkers of the renin angiotensin system (RAS), demonstrating in vivo efficacy of the drug."
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.
Results: "Of 432 screened patients, 14 were enrolled (3.5%), 9 received losartan and 5 combined control..Treatment with losartan was not associated with a difference in NCOSS slope of change in comparison with combined control (p=0.4) or placebo-only control (p=0.05) (trend favoring placebo). 60-day mortality and overall AE and SAE rates were numerically but not significantly higher with losartan."
Results: "On losartan, 24/30 (80%) experienced an adverse event as opposed to 29/30 (97%) of controls, with a lower average number of adverse events on losartan relative to control (2.2 vs 3.3). Using Poisson regression and controlling for age, sex, race, date of enrollment, disease severity at enrollment, and history of high-risk comorbidities, the incidence rate ratio of adverse events on losartan relative to control was 0.69 (95% CI: 0.49 - 0.97)
Conclusions: Losartan appeared safe for COVID-19-related acute respiratory compromise. To assess true efficacy, randomized trials are needed."
Results: "From April 2020 - February 2021, 205 participants were randomized, 101 to losartan and 104 to placebo. Compared to placebo, losartan did not significantly affect PaO2/FiO2 ratio at 7 days [difference of -24.8 (95% -55.6 to 6.1; p=0.12)]."
Results: From April-November 2020, 117 participants were randomized 58 to losartan and 59 to placebo. The primary outcome did not differ significantly between the two arms based on Barnard’s test [losartan arm: 3 events (5.2%; 95% CI 1.8-14.1%) versus placebo arm: 1 event(1.7% 95% CI 0.01-9.0%); proportion difference -3.5% (95% CI -12.7-4.5%); p=0.32]. Functional status, self-reported dyspnea, maximum daily temperatures, and viral load were not significantly different between treatment groups. Due to a lower than expected hospitalization rate and low likelihood of a clinically important treatment effect, the trial was terminated early.
Results: "..Day 5 control-group CRP levels were 6.06 ± 6.95 mg/dL (95% CI 7.79–4.35, n = 66) while telmisartan group were 3.83 ± 5.08 mg/dL (95% CI 5.08–2.59, n = 66, p = 0.038). Day 8 CRP levels were 6.30 ± 8.19 mg/dL (95% CI 8.79–3.81, n = 44) and 2.37 ± 3.47 mg/dL (95% CI 3.44–1.30, n = 43, p = 0.0098) in the control and telmisartan groups, respectively (all values expressed as mean ± SD). Kaplan-Meier analysis showed that telmisartan-treated patients had a lower median time-to-discharge (control=15 days; telmisartan=9 days). Death by day 30 was reduced in the telmisartan-treated group (control 22.54%, 16/71; telmisartan 4.29%, 3/70 participants; p = 0.0023). Composite ICU, mechanical ventilation or death was reduced by telmisartan treatment at days 15 and 30." -- Results paper.
Results: No statistically significant difference in the primary or secondary outcomes between the groups were seen. The small trial may have been unpowered to detect benefits of losartan, as there appeared to be non-statistically significant improvements in the losartan group. Additionally, as noted by the authors, in an observational study, amlodipine was associated with improved outcomes in COVID-19.
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)"
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.
"The primary endpoint of the trial was a composite endpoint of all-cause death or invasive mechanical ventilation up to 28 days or until hospital discharge. The data showed that fewer patients treated with APN01 (n=9) died or received invasive ventilation compared to placebo (n=12), although statistical significance was not achieved due to the low total number of events. Standard of care has improved dramatically since study initiation, resulting in fewer deaths and less use of nvasive mechanical ventilation than at the time of design of the study.
Secondary objectives included mechanical ventilator-free days, change in viral RNA load, improvements according to the WHO 11-Point score system and the evaluation of relevant biomarker changes following treatment with APN01. Treatment with APN01 was safe and well tolerated and no drug-related severe adverse events were observed during the study. The data demonstrated a statistically significant improvement in mechanical ventilator-free days in alive patients and reduction in viral load in the group treated with APN01 compared to placebo. APN01 also demonstrated a positive impact on key biomarkers of the renin angiotensin system (RAS), demonstrating in vivo efficacy of the drug."
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 paper.
philipn authored on Jan. 18, 2022, 11:49 p.m. 
