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

ABSTRACT

Background: The imbalance of the Renin Angiotensin System in favor of the angiotensin II has been described in Covid-19-patients. Angiotensin II regulates life processes, such as cell growth and division and can promote apoptosis initiating an inflammatory process with release of proinflammatory cytokines. Angiotensin receptor blockers (ARBs) block the AT1 receptor and could have a beneficial effect reducing Covid-19 inflammation. Purpose: To assess whether Telmisartan is effective in reducing C-reactive protein (CRP) plasma levels in hospitalized patients with Covid-19, and improves clinical outcomes and length of stay and morbimortality. Trial design: This is a parallel-group, randomized, two-arm, open-label, multicenter superiority trial with 11 allocation ratio. Methods: Inclusion criteria patients aged more than 18 years with less than 5 days of symptoms onset and after informed consent was obtained. Exclusion criteria Patients admitted to intensive care unit (ICU) or using mechanical ventilatory support or ongoing ARBs / angiotensin-converting enzyme inhibitors treatment at the time of randomization. Control arm received standard care alone and treatment arm Telmisartan 80 mg bid 14 days added to standard care. Primary outcome were CRP plasma levels at day 5 and 8 after randomization. Secondary outcomes included time to discharge at 15 days, admission to ICU and death at 15 and 30 days. Results: 158 patients were included in the analysis, 80 in the control and 78 in the telmisartan group. Day 5 control-group CRP levels were 6.06±6.95 mg/dL (n=66) while telmisartan group were 3.83±5.08 mg/dL (mean±SD;n=66, p<0.05). Day 8 CRP levels were 6.30±8.19 mg/dL (n=44) and 2.37±3.47 mg/dl (mean±SD;n=43, p<0.05) in the control and telmisartan groups, respectively. Kaplan-Meier analysis showed that Telmisartan-treated patients had lower median time to discharge (control= 15 days;telmisartan=9 days). Death by day 30 was reduced by 81% 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. No telmisartan-related adverse events were reported. Conclusions: Telmisartan, an inexpensive safe drug, in high doses, demonstrated anti-inflammatory effects and reduced morbimortality in Covid-19-hospitalized patients.