美国哈佛医学院Mandeep R Mehra团队对羟氯喹或氯喹加或不加大环内酯物治疗COVID-19的效果进行了分析。2020年5月22日，该研究发表在《柳叶刀》杂志上。

羟氯喹或氯喹联合第二代大环内酯类药物广泛用于治疗COVID-19，尽管尚无确凿证据表明有益。虽然它们用于批准的适应症（例如自身免疫性疾病或疟疾）时是安全的，但治疗COVID-19安全性和益处仍有待评估。

为了评估羟氯喹或氯喹联合或不联合大环内酯治疗COVID-19的疗效，研究组在六大洲671家医院中进行了一项研究。2019年12月20日至2020年4月14日，研究组招募了96032名实验室确诊的SARS-CoV-2阳性患者。在确诊后48小时内，将其随机分组，其中1868例接受氯喹治疗，3783例接受氯喹+大环内酯，3016例接受羟氯喹，6221例接受羟氯喹+大环内酯，其余81144例患者为对照组。

96032例COVID-19患者的平均年龄为53.8岁，女性占46.3%。在控制了多种混杂因素（年龄、性别、种族、身体质量指数、潜在的心血管疾病及其危险因素、糖尿病、潜在的肺部疾病、吸烟、免疫抑制状况和基线疾病严重性）之后，对照组的死亡率为9.3%，羟氯喹组为18.0%，羟氯喹+大环内酯组为23.8%，氯喹组为16.4%，氯喹+大环内酯组为22.2%。对照组住院期间新发室性心律失常的发生率为0.3%，羟氯喹组为6.1%，羟氯喹+大环内酯组为8.1%，氯喹组为4.3%，氯喹+大环内酯组为6.5%。

总之，羟氯喹或氯喹加或不加大环内酯治疗COVID-19无效，且降低了患者的院内生存率，增加了室性心律失常的风险。

附：英文原文

Title: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis

Author: Mandeep R Mehra, Sapan S Desai, Frank Ruschitzka, Amit N Patel

Issue&Volume: 2020-05-22

Abstract: Background

Hydroxychloroquine or chloroquine, often in combination with a second-generation macrolide, are being widely used for treatment of COVID-19, despite no conclusive evidence of their benefit. Although generally safe when used for approved indications such as autoimmune disease or malaria, the safety and benefit of these treatment regimens are poorly evaluated in COVID-19.

Methods

We did a multinational registry analysis of the use of hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19. The registry comprised data from 671 hospitals in six continents. We included patients hospitalised between Dec 20, 2019, and April 14, 2020, with a positive laboratory finding for SARS-CoV-2. Patients who received one of the treatments of interest within 48 h of diagnosis were included in one of four treatment groups (chloroquine alone, chloroquine with a macrolide, hydroxychloroquine alone, or hydroxychloroquine with a macrolide), and patients who received none of these treatments formed the control group. Patients for whom one of the treatments of interest was initiated more than 48 h after diagnosis or while they were on mechanical ventilation, as well as patients who received remdesivir, were excluded. The main outcomes of interest were in-hospital mortality and the occurrence of de-novo ventricular arrhythmias (non-sustained or sustained ventricular tachycardia or ventricular fibrillation).

Findings

96032 patients (mean age 53·8 years, 46·3% women) with COVID-19 were hospitalised during the study period and met the inclusion criteria. Of these, 14888 patients were in the treatment groups (1868 received chloroquine, 3783 received chloroquine with a macrolide, 3016 received hydroxychloroquine, and 6221 received hydroxychloroquine with a macrolide) and 81144 patients were in the control group. 10698 (11·1%) patients died in hospital. After controlling for multiple confounding factors (age, sex, race or ethnicity, body-mass index, underlying cardiovascular disease and its risk factors, diabetes, underlying lung disease, smoking, immunosuppressed condition, and baseline disease severity), when compared with mortality in the control group (9·3%), hydroxychloroquine (18·0%; hazard ratio 1·335, 95% CI 1·223–1·457), hydroxychloroquine with a macrolide (23·8%; 1·447, 1·368–1·531), chloroquine (16·4%; 1·365, 1·218–1·531), and chloroquine with a macrolide (22·2%; 1·368, 1·273–1·469) were each independently associated with an increased risk of in-hospital mortality. Compared with the control group (0·3%), hydroxychloroquine (6·1%; 2·369, 1·935–2·900), hydroxychloroquine with a macrolide (8·1%; 5·106, 4·106–5·983), chloroquine (4·3%; 3·561, 2·760–4·596), and chloroquine with a macrolide (6·5%; 4·011, 3·344–4·812) were independently associated with an increased risk of de-novo ventricular arrhythmia during hospitalisation.

Interpretation

We were unable to confirm a benefit of hydroxychloroquine or chloroquine, when used alone or with a macrolide, on in-hospital outcomes for COVID-19. Each of these drug regimens was associated with decreased in-hospital survival and an increased frequency of ventricular arrhythmias when used for treatment of COVID-19.

DOI: 10.1016/S0140-6736(20)31180-6

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31180-6/fulltext