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联盟:倡导开展前瞻性临床试验,以测试羟氯喹对COVID-19的暴露后预防潜力。

Coalition: Advocacy for prospective clinical trials to test the post-exposure potential of hydroxychloroquine against COVID-19.

作者信息

Picot Stephane, Marty Aileen, Bienvenu Anne-Lise, Blumberg Lucille H, Dupouy-Camet Jean, Carnevale Pierre, Kano Shigeyuki, Jones Malcolm K, Daniel-Ribeiro Cláudio Tadeu, Mas-Coma Santiago

机构信息

Malaria Research Unit, ICBMS, UMR 5246, CNRS, INSA, CPE University Lyon, 69100 Villeurbanne, France.

Institute of Parasitology and Medical Mycology, Croix-Rousse Hospital, Hospices Civils de Lyon, 69004 Lyon, France.

出版信息

One Health. 2020 Apr 4;9:100131. doi: 10.1016/j.onehlt.2020.100131. eCollection 2020 Jun.

Abstract

Our coalition of public health experts, doctors, and scientists worldwide want to draw attention to the need for high-quality evaluation protocols of the potential beneficial effect of hydroxychloroquine (HCQ) as a post-exposure drug for exposed people. In the absence of an approved, recognized effective pre or post-exposure prophylactic drug or vaccine for COVID-19, nor of any approved and validated therapeutic drug, coupled with social and political pressure raised by publicity both regarding the potential beneficial effect of hydroxychloroquine (HCQ) as well as potential risks from HCQ, we urge the immediate proper clinical trials. Specifically, we mean using HCQ for post-exposure of people with close contact with patients with positive COVID19 rtPCR, including home and medical caregivers. We have reviewed the mechanisms of antiviral effect of HCQ, the risk-benefit ratio taking into consideration the PK/PD of HCQ and the thresholds of efficacy. We have studied its use as an antimalarial, an antiviral, and an immunomodulating drug and concluded that the use of HCQ at doses matching that of the standard treatment of Systemic Lupus erythematous, which has proven safety and efficacy in terms of HCQ blood and tissue concentration adapted to bodyweight (2,3), at 6 mg/kg/day 1 (loading dose) followed by 5 mg/kg/ day, with a maximum limit of 600 mg/day in all cases should swiftly be clinically evaluated as a post-exposure drug for exposed people.

摘要

我们由全球公共卫生专家、医生和科学家组成的联盟希望提请注意,需要制定高质量的评估方案,以评估羟氯喹(HCQ)作为暴露后药物对接触者的潜在有益效果。目前尚无针对新冠病毒病(COVID-19)的经批准、认可有效的暴露前或暴露后预防性药物或疫苗,也没有任何经批准和验证的治疗药物,再加上关于羟氯喹(HCQ)潜在有益效果以及HCQ潜在风险的宣传所引发的社会和政治压力,我们敦促立即开展适当的临床试验。具体而言,我们指的是将HCQ用于对COVID-19 rtPCR检测呈阳性患者的密切接触者进行暴露后治疗,包括家庭护理人员和医护人员。我们审查了HCQ的抗病毒作用机制、考虑到HCQ的药代动力学/药效学及疗效阈值后的风险效益比。我们研究了其作为抗疟药、抗病毒药和免疫调节药的用途,并得出结论,以系统性红斑狼疮标准治疗剂量使用HCQ,该剂量在根据体重调整的HCQ血液和组织浓度方面已证明具有安全性和有效性(2,3),即6毫克/千克/天1(负荷剂量),随后为5毫克/千克/天,所有情况下最大剂量限制为600毫克/天,应迅速作为暴露后药物对接触者进行临床评估。

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