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.

Abstract

There is much debate on the use of angiotensin receptor blockers (ARBs) in severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-infected patients. Although 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 multicenter, 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 end point 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 160 mg bid, and the placebo arm will receive matching placebo. Treatment duration will be 14 days, or until the occurrence of the primary end point 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.

• Authors: D H Frank Gommans, Joris Nas, Sara-Joan Pinto-Sietsma, Yvonne Koop, Regina E Konst, Frans Mensink, Goaris W A Aarts, Lara S F Konijnenberg, Kimberley Cortenbach, Dominique V M Verhaert, Jos Thannhauser, Jan-Quinten Mol, Maxim J P Rooijakkers, Jacqueline L Vos, Anouke van Rumund, Priya Vart, Robert-Jan Hassing, Jan-Hein Cornel, C Peter C de Jager, Michel M van den Heuvel, Hans G van der Hoeven, Annelies Verbon, Yigal M Pinto, Niels van Royen, Roland R J van Kimmenade, Event committee, Peter W de Leeuw, Michiel A van Agtmael, Paul Bresser, Data Safety Monitoring Board, Wiek H van Gilst, Anton Vonk-Noordergraaf, Jan G P Tijssen, Steering committee, Niels van Royen, C Peter C de Jager, Michel M van den Heuvel, Hans G van der Hoeven, Annelies Verbon, Yigal M Pinto, Roland R J van Kimmenade
• Journal: American heart journal (Am Heart J) Vol. 226 Pg. 60-68 (08 2020) ISSN: 1097-6744 [Electronic] United States
• PMID: 32512291 (Publication Type: Clinical Trial Protocol, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Placebos
• Valsartan

Topics

• Adult
• Angiotensin II Type 1 Receptor Blockers (administration & dosage, therapeutic use)
• Betacoronavirus
• COVID-19
• Coronary Care Units
• Coronavirus Infections (complications, mortality)
• Double-Blind Method
• Drug Administration Schedule
• Humans
• Inpatients
• Multicenter Studies as Topic
• Netherlands
• Pandemics
• Placebos (therapeutic use)
• Pneumonia, Viral (complications, mortality)
• Randomized Controlled Trials as Topic
• Respiration, Artificial
• Respiratory Distress Syndrome (mortality, prevention & control)
• SARS-CoV-2
• Time Factors
• Valsartan (administration & dosage, therapeutic use)