Lobo Suzana Margareth, Plantefève Gaétan, Nair Girish, Joaquim Cavalcante Adilson, Franzin de Moraes Nara, Nunes Estevao, Barnum Otis, Berdun Stadnik Claudio Marcel, Lima Maria Patelli, Lins Muriel, Hajjar Ludhmila Abrahao, Lipinski Christopher, Islam Shaheen, Ramos Fabiano, Simon Tiago, Martinot Jean-Benoît, Guimard Thomas, Desclaux Arnaud, Lioger Bertrand, Neuenschwander Fernando Carvalho, DeSouza Paolino Bruno, Amin Alpesh, Acosta Samuel Amil, Dilling Daniel Forde, Cartagena Edgardo, Snyder Brian, Devaud Edouard, Barreto Berselli Marinho Ana Karolina, Tanni Suzana, Milhomem Beato Patricia Medeiros, De Wit Stephan, Selvan Vani, Gray Jeffrey, Fernandez Ricardo, Pourcher Valérie, Maddox Lee, Kay Richard, Azbekyan Anait, Chabane Mounia, Tourette Cendrine, Esmeraldino Luis Everton, Dilda Pierre J, Lafont René, Mariani Jean, Camelo Serge, Rabut Sandrine, Agus Samuel, Veillet Stanislas, Dioh Waly, van Maanen Rob, Morelot-Panzini Capucine
Intensive Care Division. Faculdade de Medicina de São José do Rio Preto, São Paulo, Brazil.
Intensive Care Unit, Clinical Research Center and CRICS-Triggersep Network, Centre Hospitalier Victor Dupouy, 69 rue du lieutenant-colonel Prudhon, 95100, Argenteuil, France.
EClinicalMedicine. 2024 Jan 3;68:102383. doi: 10.1016/j.eclinm.2023.102383. eCollection 2024 Feb.
SARS-CoV-2 binding to ACE2 is potentially associated with severe pneumonia due to COVID-19. The aim of the study was to test whether Mas-receptor activation by 20-hydroxyecdysone (BIO101) could restore the Renin-Angiotensin System equilibrium and limit the frequency of respiratory failure and mortality in adults hospitalized with severe COVID-19.
Double-blind, randomized, placebo-controlled phase 2/3 trial. Randomization: 1:1 oral BIO101 (350 mg BID) or placebo, up to 28 days or until an endpoint was reached. Primary endpoint: mortality or respiratory failure requiring high-flow oxygen, mechanical ventilation, or extra-corporeal membrane oxygenation. Key secondary endpoint: hospital discharge following recovery (ClinicalTrials.gov Number, NCT04472728).
Due to low recruitment the planned sample size of 310 was not reached and 238 patients were randomized between August 26, 2020 and March 8, 2022. In the modified ITT population (233 patients; 126 BIO101 and 107 placebo), respiratory failure or early death by day 28 was 11.4% lower in the BIO101 (13.5%) than in the placebo (24.3%) group, (p = 0.0426). At day 28, proportions of patients discharged following recovery were 80.1%, and 70.9% in the BIO101 and placebo group respectively, (adjusted difference 11.0%, 95% CI [-0.4%, 22.4%], p = 0.0586). Hazard Ratio for time to death over 90 days: 0.554 (95% CI [0.285, 1.077]), a 44.6% mortality reduction in the BIO101 group (not statistically significant). Treatment emergent adverse events of respiratory failure were more frequent in the placebo group.
BIO101 significantly reduced the risk of death or respiratory failure supporting its use in adults hospitalized with severe respiratory symptoms due to COVID-19.
Biophytis.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）与血管紧张素转换酶2（ACE2）结合可能与新型冠状病毒肺炎（COVID-19）所致重症肺炎相关。本研究旨在测试20-羟基蜕皮甾酮（BIO101）激活Mas受体是否能恢复肾素-血管紧张素系统平衡，并降低因重症COVID-19住院的成人呼吸衰竭发生率和死亡率。
双盲、随机、安慰剂对照2/3期试验。随机分组：1:1口服BIO101（350毫克，每日两次）或安慰剂，最长28天或直至达到终点。主要终点：死亡率或需要高流量吸氧、机械通气或体外膜肺氧合的呼吸衰竭。关键次要终点：康复后出院（ClinicalTrials.gov注册号，NCT04472728）。
由于入组率低，未达到计划的310例样本量，2020年8月26日至2022年3月8日期间有238例患者被随机分组。在改良意向性分析人群（233例患者；126例使用BIO101，107例使用安慰剂）中，BIO101组第28天呼吸衰竭或早期死亡发生率（13.5%）比安慰剂组（24.3%）低11.4%，（p = 0.0426）。第28天时BIO101组和安慰剂组康复后出院患者比例分别为80.1%和70.9%，（校正差异11.0%，95%置信区间[-0.4%，22.4%]，p = 0.0586）。90天内死亡时间的风险比为：0.554（95%置信区间[0.285，1.077]），BIO101组死亡率降低44.6%（无统计学意义）。安慰剂组呼吸衰竭的治疗中出现的不良事件更常见。
BIO101显著降低了死亡或呼吸衰竭风险，支持其用于因COVID-严重呼吸症状住院的成人患者。
Biophytis公司。
Zotero 插件