Kalfon Pierre, Payen Jean-François, Rousseau Alexandra, Chousterman Benjamin, Cachanado Marine, Tibi Annick, Audibert Juliette, Depret François, Constantin Jean-Michel, Weiss Emmanuel, Remerand Francis, Freund Yonathan, Simon Tabassome, Riou Bruno
Service de Réanimation polyvalente, Hôpital Louis Pasteur, Centre Hospitalier de Chartres, Le Coudray, France.
Department of Anesthesiology and Intensive Care, Grenoble Alpes University Hospital, and Grenoble Alpes University, Grenoble Institut des Neurosciences, INSERM U1216, Grenoble, France.
EClinicalMedicine. 2022 Oct;52:101663. doi: 10.1016/j.eclinm.2022.101663. Epub 2022 Sep 21.
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.
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.min) almitrine or placebo. The primary outcome was endotracheal intubation for MV or death within 7 days after randomisation. Secondary outcomes included in-hospital mortality, 28-day mortality, number of ventilator-free days, number of days in the ICU and the hospital, and treatment discontinuation for pre-specified adverse effects. This trial was registered with ClinicalTrials.gov, NCT04357457.
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.
In patients with COVID-19 acute hypoxemic respiratory failure, low-dose almitrine failed in reducing the need for MV or death at day 7.
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.
新型冠状病毒肺炎（COVID-19）患者的严重低氧血症可能源于缺氧性肺血管收缩，导致通气/血流比值（V/Q）失调。由于烯丙哌三嗪可改善V/Q，它可能降低此类患者机械通气（MV）的风险。我们的主要目标是确定烯丙哌三嗪在第7天对MV需求的影响。
在一项涉及15个重症监护病房（ICU）的随机双盲安慰剂对照试验中，因COVID-19肺炎住院且发生急性低氧性呼吸衰竭的患者被随机分配接受5天静脉注射低剂量（2µg·kg·min）烯丙哌三嗪或安慰剂。主要结局是随机分组后7天内进行MV的气管插管或死亡。次要结局包括院内死亡率、28天死亡率、无呼吸机天数、在ICU和医院的天数，以及因预先指定的不良反应而停药。该试验已在ClinicalTrials.gov注册，注册号为NCT04357457。
在2020年9月3日至2021年9月25日期间，181例患者入组并随机分配至烯丙哌三嗪组（n = 89）或安慰剂组（n = 92）。179例患者（不包括两名退出研究的患者）纳入意向性分析（平均年龄：60.1岁；34%为女性）并进行分析。在第7天，主要终点事件发生在32例接受烯丙哌三嗪治疗的患者中（36%）和37例接受安慰剂治疗的患者中（41%），差异为-4.3%（95%置信区间：-18.7%至10.2%）。两组的次要结局（28天死亡率、院内死亡率、第28天的无呼吸机天数、在ICU和医院的天数，以及因预先指定的不良反应而停药）无差异。
在COVID-19急性低氧性呼吸衰竭患者中，低剂量烯丙哌三嗪未能降低第7天对MV的需求或死亡率。
由法国卫生部资助的临床研究医院项目（PHRC COVID 2020），法国施维雅实验室（法国叙雷讷）免费提供研究药物。
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