Background

Colchicine has been proposed as a treatment for COVID-19 based on its anti-inflammatory actions. We aimed to evaluate the efficacy and safety of colchicine in patients admitted to hospital with COVID-19.

Methods

In this streamlined, randomised, controlled, open-label trial, underway at 177 hospitals in the UK, two hospitals in Indonesia, and two hospitals in Nepal, several possible treatments were compared with usual care in patients hospitalised with COVID-19. Patients were eligible for inclusion in the study if they were admitted to hospital with clinically suspected or laboratory confirmed SARS-CoV-2 infection and had no medical history that might, in the opinion of the attending clinician, put the patient at significant risk if they were to participate in the trial. Eligible and consenting adults were randomly assigned (1:1) to receive either usual standard of care alone (usual care group) or usual standard of care plus colchicine (colchicine group) using web-based simple (unstratified) randomisation with allocation concealment. Participants received colchicine 1 mg after randomisation followed by 500 μg 12 h later and then 500 μg twice a day by mouth or nasogastric tube for 10 days in total or until discharge. Dose frequency was halved for patients receiving a moderate CYP3A4 inhibitor (eg, diltiazem), patients with an estimated glomerular filtration rate of less than 30 mL/min per 1·73m², and those with an estimated bodyweight of less than 70 kg. The primary outcome was 28-day mortality, secondary endpoints included time to discharge, the proportion of patients discharged from hospital within 28 days, and, in patients not on invasive mechanical ventilation at randomisation, a composite endpoint of invasive mechanical ventilation or death. All analyses were by intention-to-treat. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.

Findings

Between Nov 27, 2020, and March 4, 2021, 11 340 (58%) of 19 423 patients enrolled into the RECOVERY trial were eligible to receive colchicine; 5610 (49%) patients were randomly assigned to the colchicine group and 5730 (51%) to the usual care group. Overall, 1173 (21%) patients in the colchicine group and 1190 (21%) patients in the usual care group died within 28 days (rate ratio 1·01 [95% CI 0·93 to 1·10]; p=0·77). Consistent results were seen in all prespecified subgroups of patients. Median time to discharge alive (10 days [IQR 5 to >28]) was the same in both groups, and there was no significant difference in the proportion of patients discharged from hospital alive within 28 days (3901 [70%] patients in the colchicine group and 4032 [70%] usual care group; rate ratio 0·98 [95% CI 0·94 to 1·03]; p=0·44). In those not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (1344 [25%] in the colchicine group vs 1343 [25%] patients in the usual care group; risk ratio 1·02 [95% CI 0·96 to 1·09]; p=0·47).

Interpretation

In adults hospitalised with COVID-19, colchicine was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death.

Funding

UK Research and Innovation (Medical Research Council), National Institute of Health Research, and Wellcome Trust.

中文翻译：

---

秋水仙碱用于治疗 COVID-19 入院患者（恢复）：一项随机、对照、开放标签平台试验

 背景

基于其抗炎作用，秋水仙碱被提议作为 COVID-19 的治疗方法。我们的目的是评估秋水仙碱对住院的 COVID-19 患者的疗效和安全性。

 方法

这项简化、随机、对照、开放标签的试验在英国 177 家医院、印度尼西亚两家医院和尼泊尔两家医院进行，对住院的 COVID-19 患者的几种可能的治疗方法与常规治疗进行了比较。如果患者入院时患有临床怀疑或实验室确诊的 SARS-CoV-2 感染，并且没有主治临床医生认为可能使患者面临重大风险的病史，则患者有资格参与研究。是要参加审判。符合条件并同意的成年人被随机分配（1:1），接受单独的常规标准护理（常规护理组）或常规标准护理加秋水仙碱（秋水仙碱组），使用基于网络的简单（非分层）随机分配和分配隐藏。参与者在随机分组后接受 1 mg 秋水仙碱，12 小时后接受 500 μg，然后通过口服或鼻胃管每天两次 500 μg，总共 10 天或直至出院。对于接受中度CYP3A4抑制剂（例如地尔硫卓）的患者、估计肾小球滤过率小于30 mL/min/1·73m ²的患者以及估计体重小于70 kg的患者，剂量频率减半。主要终点是 28 天死亡率，次要终点包括出院时间、28 天内出院患者的比例，以及在随机分组中未接受有创机械通气的患者中，有创机械通气或死亡的复合终点。所有分析均按意向治疗进行。该试验已在 ISRCTN（50189673）和 ClinicalTrials.gov（NCT04381​​936）注册。

 发现

2020年11月27日至2021年3月4日期间，参加RECOVERY试验的19 423名患者中有11 340名（58％）有资格接受秋水仙碱治疗； 5610 名患者（49%）被随机分配到秋水仙碱组，5730 名患者（51%）被分配到常规护理组。总体而言，秋水仙碱组中有 1173 名患者 (21%) 和常规护理组有 1190 名患者 (21%) 在 28 天内死亡（比率为 1·01 [95% CI 0·93 至 1·10]；p=0 ·77）。在所有预先指定的患者亚组中都观察到了一致的结果。两组中存活出院的中位时间（10 天 [IQR 5 至 >28]）相同，并且 28 天内存活出院的患者比例没有显着差异（2017 年有 3901 名患者[70%]）秋水仙碱组和 4032 [70%] 常规护理组；比率为 0·98 [95% CI 0·94 至 1·03]；p=0·44）。在基线时未接受有创机械通气的患者中，达到有创机械通气复合终点或死亡的比例没有显着差异（秋水仙碱组有1344 名患者 [25%]，常规护理组有 1343 名患者 [25%]） ; 风险比 1·02 [95% CI 0·96 至 1·09]；p=0·47）。

 解释

在因 COVID-19 住院的成人中，秋水仙碱与 28 天死亡率、住院时间或进展为有创机械通气或死亡风险的降低无关。

 资金

英国研究与创新（医学研究委员会）、国家健康研究所和威康信托基金。