Lovre Dragana, Bateman Kristin, Sherman Mya, Fonseca Vivian A, Lefante John, Mauvais-Jarvis Franck
Section of Endocrinology and Metabolism, John W. Deming Department of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana, USA.
Section of Endocrinology, Department of Medicine, Southeast Louisiana Veterans Health Care System, New Orleans, Louisiana, USA.
BMJ Open. 2021 Nov 30;11(11):e053684. doi: 10.1136/bmjopen-2021-053684.
As of November 2021, COVID-19 has killed more than 5 million people globally, including over 750 000 in the USA. Apart from corticosteroids, most available therapeutic options are at best marginally efficient in reducing disease severity and are extremely expensive. The systematic investigation of clinically approved drugs is a priority to determine what does mitigate disease severity. Oestradiol (E2) and progesterone (P4) produce a state of anti-inflammatory immune responses and immune tolerance, and enhanced antibody production. The goal of this trial is to evaluate the efficacy of a short E2 and P4 therapy, in addition to standard of care (SOC), in mitigating disease severity in COVID-19 hospitalised patients.
Phase 2, randomised, double blind, placebo-controlled, single-centre trial. Patients hospitalised for confirmed COVID-19, with scores 3-5 on the 9-point WHO ordinal scale are randomised between two arms: (1) Oestradiol cypionate intramuscular (IM) and micronised progesterone oral (PO), in addition to SOC, and (2) placebo, in addition to SOC. The primary outcome is the proportion of patients improving to scores 1 or 2 on the WHO scale through day 28. Secondary outcomes include length of hospital stay, duration of mechanical ventilation, cause of death, readmission rates, change in inflammatory biomarkers between admission and occurrence of primary endpoint, and adverse events. Study sample size will be up to 120 participants. The trial is currently recruiting subjects.
The sponsor of this study is the Center of Excellence in Sex-Based Biology & Medicine at Tulane University, New Orleans, Louisiana, USA. Ethical approval was obtained from the Tulane institutional review board on 14 May 2021. The study was reviewed by the US Food and Drug Administration and granted Investigational New Drug #152 499. Results of the study will be submitted for publication in a peer-reviewed journal.
NCT04865029; Pre-results.
截至2021年11月，新冠病毒已在全球造成超过500万人死亡，其中美国超过75万人。除皮质类固醇外，大多数现有的治疗选择在减轻疾病严重程度方面效果甚微，而且极其昂贵。对临床批准药物进行系统研究是确定哪些药物能真正减轻疾病严重程度的当务之急。雌二醇（E2）和孕酮（P4）可产生抗炎免疫反应和免疫耐受状态，并增强抗体产生。本试验的目的是评估在标准治疗（SOC）基础上，短期使用E2和P4治疗对减轻新冠病毒住院患者疾病严重程度的疗效。
2期、随机、双盲、安慰剂对照、单中心试验。确诊为新冠病毒感染且在世界卫生组织9分序贯量表上得分为3 - 5分的住院患者被随机分为两组：（1）除SOC外，接受环戊丙酸雌二醇肌肉注射（IM）和微粉化孕酮口服（PO）治疗；（2）除SOC外，接受安慰剂治疗。主要结局是到第28天时在世界卫生组织量表上改善到1分或2分的患者比例。次要结局包括住院时间、机械通气持续时间、死亡原因、再入院率、入院时与主要终点发生时炎症生物标志物的变化以及不良事件。研究样本量最多为120名参与者。该试验目前正在招募受试者。
本研究的主办方是美国路易斯安那州新奥尔良市杜兰大学基于性别的生物学与医学卓越中心。2021年5月14日获得了杜兰大学机构审查委员会的伦理批准。该研究经美国食品药品监督管理局审查并获得研究性新药#152 499。研究结果将提交至同行评审期刊发表。
NCT04865029；预结果。
