Effect of intravenous almitrine on intubation or mortality in patients with COVID-19 acute hypoxemic respiratory failure: A multicentre, randomised, double-blind, placebo-controlled trial.

Background

Severe hypoxemia in patients with COVID-19 pneumonia might result from hypoxic pulmonary vasoconstriction, contributing to ventilation/perfusion (V/Q) mismatch. Because almitrine improves V/Q, it might reduce the risk for mechanical ventilation (MV) in such patients. Our primary objective was to determine the effect of almitrine on the need for MV at day 7.

Methods

In a randomised double-blind placebo-controlled trial involving 15 ICUs, patients hospitalized for COVID-19 pneumonia and experiencing acute hypoxemic respiratory failure were randomly assigned to receive 5 days of intravenous low-dose (2 µg.kg

Findings

Between September 3, 2020 and September 25, 2021 181 patients were enrolled and randomly assigned to almitrine (n=89) or placebo (n=92). 179 patients (excluding two who withdrew from the study) were included in the intention-to-treat analysis (mean age: 60·1 years; 34% women) and analyzed. On day 7, the primary endpoint occurred in 32 patients assigned to almitrine (36%) and in 37 patients assigned to placebo (41%), for a difference of -4·3% (95% confidence interval: -18·7% to 10·2%). Secondary outcomes (28-day mortality, in-hospital mortality, ventilator-free days at day 28, days in the ICU and the hospital, and treatment discontinuation for pre-specified adverse effects) did not differ between the two groups.

Interpretation

In patients with COVID-19 acute hypoxemic respiratory failure, low-dose almitrine failed in reducing the need for MV or death at day 7.

Funding

Programme Hospitalier de Recherche Clinique (PHRC COVID 2020) funded by the French Ministry of Health, Les Laboratoires Servier (Suresnes, France) providing the study drug free of charge.

Informations de copyright

© 2022 The Authors.

Déclaration de conflit d'intérêts

PK received personal fees from General Electric Healthcare outside of the submitted work. JFP: Nothing to disclose. AR: Nothing to disclose. BC: Nothing to disclose. MC: Nothing to disclose. AT: Nothing to disclose. JA: Nothing to disclose. FD: personal fees from Sedana medical and Biomerieux; research grant from French Ministry of Health, European Society of Intensive Care Medicine, and Société Française d'Anesthésie Réanimation. JMC: personal fees and non-financial support from Drager, GE Healthcare, Sedana Medical, Baxter, and Amomed; personal fees from Fisher and Paykel Healthcare, Orion, Philips Medical, and Fresenius Medical Care; and nonfinancial support from LFB and Bird Corporation, outside of the submitted work. EW: personal fees from MSD, Akcea therapeutics, and LFB; nonfinancial support from LFB and Akcea therapeutics, outside of the submitted work. FR: Nothing to disclose. YF: Nothing to disclose. TS: research grants or contracts from AstraZeneca, Bayer, Boehringer, Daiichi-Sankyo, Eli-Lilly, GSK, Novartis, and Sanofi; personal fees from Servier, and Novartis; participation on a Data Safety Monitoring Board or Advisory Board from Ablative solutions, Air Liquide, AstraZeneca, Sanofi, Novartis, and 4Living Biotech, outside of the submitted work. BR: Nothing to disclose.