EFFICACY OF INTRAVENOUS ALMITRINE IN REDUCING THE NEED FOR MECHANICAL VENTILATION IN PATIENTS WITH HYPOXEMIC ACUTE RESPIRATORY FAILURE DUE TO COVID-19-RELATED PNEUMONIA: a RANDOMIZED CONTROLLED DOUBLE-BLIND STUDYFROM THE SKIP-ICU CONSORTIUM

INTERVENTION: Trade Name: VECTARION INJECTABLE, lyophilisat et solution pour préparation injectable Product Name: Almitrine (DCI) bis mésilate Pharmaceutical Form: Lyophilisate for solution for injection Pharmaceutical form of the placebo: Solution for injection Route of administration of the placebo: Intravenous use CONDITION: Patients with hypoxemic acute respiratory failure due to COVID‐19‐related pneumonia Therapeutic area: Diseases [C] ‐ Virus Diseases [C02] PRIMARY OUTCOME: Main Objective: To assess the efficacy of 5‐day almitrine therapy (2 µg.kg‐1.min‐1) in reducing the need for mechanical invasive ventilation in patients with hypoxemic respiratory failure due to COVID‐19‐related pneumonia at seven days Primary end point(s): Endotracheal intubation within 7 days after randomization. Death will be considered as a failure (endotracheal intubation). Secondary Objective: To assess the efficacy of intravenous almitrine in reducing: ; ‐in‐hospital mortality ; ‐28‐day all‐cause mortality ; ‐duration of mechanical ventilation; ‐hospitalization rate in the ICU ; ‐length of stay in the ICU; ‐hospital length of stay ; To assess safety and side effects of intravenous almitrine; Timepoint(s) of evaluation of this end point: Day 7 SECONDARY OUTCOME: Secondary end point(s): ‐ 28‐day mortality ; ‐ In‐hospital mortality ; ‐ Number of ventilator‐free days between at day 28 ; ‐ Number of days in the ICU ; ‐ Number of days in the hospital ; ‐ Safety assessment: discontinuation rate of the treatment for arterial lactate more than 4 mmol/L, ALT/AST levels greater then 3 times the upper limit, and diagnosis of pulmonary arterial hypertension or acute cor pulmonale documented by echocardiography Timepoint(s) of evaluation of this end point: Day 28 INCLUSION CRITERIA: ‐ Adults patients aged 75 years of less ‐ COVID‐19 diagnosis in the past 14 days defined as either positive rt‐PCR for SARS‐cov2 or compatible or lesion in lung in CT (consistent or typical for covid19) or positive serology ‐ Hypoxemic respiratory failure with the following criteria: oxygen saturation level of 92% or less, as measured by pulsed oximetry (SpO2) under oxygen therapy with an oxygen rate of 6 L/min or more. ‐ Hospital admission within 14 days ‐ Patients affiliated to French social security (“AMEâ€� excepted) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 106 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 106