Telmisartan for treatment of Covid-19 patients: An open multicenter randomized clinical trial

Abstract

Background: Angiotensin receptor blockers (ARBs), such as telmisartan, have been postulated to treat Covid-19-induced lung inflammation. Methods: This is a parallel-group, randomized, two-arm, open-label, adaptive, multicenter superiority trial with 1:1 allocation ratio. Participants included patients from 18 years of age hospitalized with Covid-19 with 4 or fewer days since symptom onset enrolled at a university and a community hospital in Buenos Aires, Argentina. Exclusion criteria included prior intensive care unit (ICU) admission and use of ARBs/angiotensin converting enzyme inhibitors at randomization. Control arm received standard care alone and treatment arm telmisartan 80 mg twice daily for 14 days. Primary outcomes were C-reactive protein (CRP) plasma levels at day 5 and 8 after randomization. Secondary outcomes included time to discharge within 15 days, admission to ICU and death at 15-and 30-days. NCT04355936 (Completed). Findings: A pragmatic decision to end the study before the third interim analysis was made on Oct. 30th due to sharp reduction in recruitment. A total of 162 patients were randomized. 158 patients enrolled between May 14 and October 30 2020, were included in the analysis, 80 in the standard care and 78 in the telmisartan added to standard care group. Baseline absolute CRP serum levels were 5.53 § 6.19 mg/dL (95% CI 6.91 to 4.15, n = 80) and 9.04 § 7.69 (95% CI 9.04 to 10.82, n = 74) in the standard care and telmisartan added to standard care groups, respectively. Day 5 control-group CRP levels were 6.06 § 6.95 mg/dL (95% CI 7.79À4.35, n = 66) while telmisartan group were 3.83 § 5.08 mg/dL (95% CI 5.08À2.59, n = 66, p = 0.038). Day 8 CRP levels were 6.30 § 8.19 mg/dL (95% CI 8.79À3.81, n = 44) and 2.37 § 3.47 mg/dL (95% CI 3.44À1.30, 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%,

Renin Angiotensin System Inhibition as treatment for Covid-19?

“…In EClinicalMedicine, Duarte and colleagues report the first phase 2 RCT evaluating treatment of hospitalised Covid-19 patients with an ARB, telmisartan, versus usual care, in an open label study in Argentina [10]. The results are very intriguing.…”

ACE2-like carboxypeptidase B38-CAP protects from SARS-CoV-2-induced lung injury

“…B38-CAP as an ACE2-like enzyme, but not as a decoy for the virus, improves the symptoms of SARS-CoV-2-induced lung injury as well as virus-free Spike-augmented lung injury. These results have important therapeutic implications to use rshACE2 or RAS inhibitors for COVID-19 patients, for which bene cial outcomes have recently been suggested in clinical studies 28,29 .…”

“…Accordingly, it would be speculated that therapeutics to suppress the RAS, such as angiotensin-receptor blocker (ARB) and ACE inhibitor, might be also bene cial for COVID-19 patients. In fact, although initial epidemiological studies showed that medication of ARB or ACE inhibitor did not affect infectivity of SARS-CoV-2 and severity of COVID-19 in the patients [42][43][44] , recent clinical studies have suggested that ARB or ACE inhibitor provide better prognosis to the patients 28,29 . The enzymatic activity of both B38-CAP and ACE2 does not only degrade Ang II but also generates Ang 1-7, which is protective against lung injury through activation of the Mas receptor 45 .…”

Receptor Interactions of Angiotensin II and Angiotensin Receptor Blockers—Relevance to COVID-19

“…The protective effects of ARBs against SARS-CoV-2 infection was further validated and confirmed in a recent open multicenter randomized clinical trial using the ARB telmisartan and has been postulated to treat coronavirus 2019 (COVID19)-induced lung inflammation [20]. Telmisartan is the strongest binder among all ARBs, and it appears to disrupt the binding between the receptor-binding domain of the spike protein and ACE2 [21].…”