GHU Paris Psychiatrie et neurosciences, Service de Neuroanesthésie Neuroréanimation, Paris, France.
Univeristé de Paris, Paris, France.
Trials. 2021 Feb 28;22(1):170. doi: 10.1186/s13063-021-05118-7.
As of mid-June 2020, 7,500,000 people were infected with SARS-CoV-2 worldwide and 420,000 people died, mainly from coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS). COVID-19-related ARDS is subject to a mortality rate of 50% and prolonged period of mechanical ventilation, with no specific pharmacological treatment currently available (Infection au nouveau Coronavirus (SARS-CoV-2), COVID-19, France et Monde. https://www.santepubliquefrance.fr/dossiers/coronavirus-covid-19 ). Because of its immunomodulatory action, we propose to evaluate the efficacy and safety of intravenous immunoglobulin (IVIG) administration in patients developing COVID-19-related ARDS.
The trial is a phase III double-blind, randomized, multicenter, parallel group, concurrent, controlled study in hospitalized participants with COVID-19 requiring mechanical ventilation using a sequential design. Participants in the treatment group will receive infusions of polyvalent immunoglobulin for 4 consecutive days, and the placebo group will receive an equivalent volume of sodium chloride 0.9% for the same duration. The primary outcome is the number of ventilator-free days up to the 28th day. Secondary objectives are to evaluate the effect of IVIG on (1) organ failure according to the Sequential Organ Failure Assessment (SOFA) score at 14 and 28 days, (2) lung injury score at 14 and 28 days, (3) the occurrence of grade 3 or 4 adverse events of IVIG, (4) length of intensive care unit (ICU) stay, (5) length of hospital stay, (6) functional outcomes at day 90 defined by the activities of daily living and instrumental activities of the daily living scales, and (7) 90-day survival. One hundred thirty-eight subjects will be randomized in a 1:1 ratio to IVIG or placebo groups (69 in each group), considering 90% power, alpha level 0.05 (two sides), and 0.67 effect size level.
The ICAR trial investigates the effect of IVIG in COVID-19-related ARDS. We expect an increase in the survival rate and a reduction in the duration of mechanical ventilation, which is associated with significant morbidity.
EudraCT 2020-001570-30. ClinicalTrials.gov NCT04350580 . Registered on 17 April 2020.
截至 2020 年 6 月中旬，全球有 750 万人感染了 SARS-CoV-2，42 万人死亡，主要死于与 2019 年冠状病毒病（COVID-19）相关的急性呼吸窘迫综合征（ARDS）。COVID-19 相关的 ARDS 的死亡率为 50%，需要长时间进行机械通气，目前尚无特定的药物治疗方法（新出现的冠状病毒（SARS-CoV-2）感染，COVID-19，法国和世界。https://www.santepubliquefrance.fr/dossiers/coronavirus-covid-19）。由于其免疫调节作用，我们建议评估静脉注射免疫球蛋白（IVIG）在发生 COVID-19 相关 ARDS 的患者中的疗效和安全性。
该试验是一项在住院的 COVID-19 患者中进行的 III 期双盲、随机、多中心、平行组、同期、对照研究，采用序贯设计。治疗组患者将接受 4 天的多价免疫球蛋白输注，对照组患者将接受相同时间的 0.9%氯化钠等效体积。主要结局是第 28 天前无呼吸机天数。次要目标是评估 IVIG 对（1）14 天和 28 天根据序贯器官衰竭评估（SOFA）评分的器官衰竭的影响，（2）14 天和 28 天的肺损伤评分，（3）IVIG 发生 3 级或 4 级不良事件的发生率，（4）重症监护病房（ICU）入住时间，（5）住院时间，（6）第 90 天由日常生活活动和日常生活活动工具量表定义的功能结局，以及（7）90 天存活率。将 138 名受试者按 1:1 的比例随机分为 IVIG 或安慰剂组（每组 69 名），考虑到 90%的效力、alpha 水平为 0.05（双侧）和 0.67 效应大小水平。
ICAR 试验研究了 IVIG 在 COVID-19 相关 ARDS 中的作用。我们预计生存率会提高，机械通气时间会缩短，这与显著的发病率有关。
EudraCT 2020-001570-30。ClinicalTrials.gov NCT04350580. 2020 年 4 月 17 日注册。
