Rationale and design of the PRAETORIAN-COVID trial: A double-blind, placebo-controlled randomized clinical trial with valsartan for PRevention of Acute rEspiraTORy dIstress syndrome in hospitAlized patieNts with SARS-COV-2 Infection Disease()

Gommans, D.H. Frank; Nas, Joris; Pinto-Sietsma, Sara-Joan; Koop, Yvonne; Konst, Regina E.; Mensink, Frans; Aarts, Goaris W.A.; Konijnenberg, Lara S.F.; Cortenbach, Kimberley; Verhaert, Dominique V.M.; Thannhauser, Jos; Mol, Jan-Quinten; Rooijakkers, Maxim J.P.; Vos, Jacqueline L.; van Rumund, Anouke; Vart, Priya; Hassing, Robert-Jan; Cornel, Jan-Hein; de Jager, C. Peter C.; van den Heuvel, Michel M.; van der Hoeven, Hans G.; Verbon, Annelies; Yigal, M.; van Royen, Niels; van Kimmenade, Roland R.J.; de Leeuw, Peter W.; van Agtmael, Michiel A.; Bresser, Paul; van Gilst, Wiek H.; Vonk-Noordergraaf, Anton; Tijssen, Jan G.P.; van Royen, Niels; de Jager, C. Peter C.; van den Heuvel, Michel M.; van der Hoeven, Hans G.; Verbon, Annelies; Pinto, Yigal M.; van Kimmenade, Roland R.J.

BACKGROUND: There is much debate on the use of angiotensin receptor blockers (ARBs) in SARS-CoV-2 infected patients. While it has been suggested that ARBs might lead to a higher susceptibility and severity of SARS-CoV-2 infection, experimental data suggest that ARBs may reduce acute lung injury via blocking angiotensin-II-mediated pulmonary permeability, inflammation and fibrosis. However, despite these hypotheses, specific studies on ARBs in SARS-CoV-2 patients are lacking. METHODS: The PRAETORIAN-COVID trial is a multi-center, double-blind, placebo-controlled 1:1 randomized clinical trial in adult hospitalized SARS-CoV-2-infected patients (n=651). The primary aim is to investigate the effect of the ARB valsartan compared to placebo on the composite endpoint of admission to an intensive care unit, mechanical ventilation or death, within 14 days of randomization. The active-treatment arm will receive valsartan in a dosage titrated to blood pressure up to a maximum of 160mg b.i.d. and the placebo arm will receive matching placebo. Treatment duration will be 14 days; or until the occurrence of the primary endpoint, or until hospital discharge, if either of these occurs within 14 days. The trial is registered at clinicaltrials.gov (NCT04335786, 2020). SUMMARY: The PRAETORIAN-COVID trial is a double-blind, placebo-controlled 1:1 randomized trial to assess the effect of valsartan compared to placebo on the occurrence of ICU admission, mechanical ventilation and death in hospitalized SARS-CoV-2 infected patients. The results of this study might impact the treatment of SARS-CoV-2 patients globally.