本文為COVID-19患者恩慈使用(compassionate use)瑞德西韋(Remdesivir)恩慈使用(compassionate use)的跨國病例報告。收案的標準包含不需要額外提供氧氣或是需要使用侵入性或非侵入性氧氣治療、肝腎功能正常,且經rt-PCR確診的新冠患者。治療方式是第一天注射200mg,之後的9天每天給予100mg,共10天的療程。使用期間從1月25日到3月7日。

排除8人因為資料不完全或是給藥劑量有誤,最後納入53例進行分析。53位患者包括來自美國(22位)、歐洲/加拿大(22位)及日本(9位)。除了2位患者不需要額外提供氧氣外,其餘絕大多數皆是需要使用氧氣治療的中重度患者;其中30名(57%)需要插管使用呼吸器、4名(8%)需要使用葉克膜。40名(75%)接受了完整的10天療程、10名(19%)接受了5-9天的治療、3名(6%)接受治療少於5天。  

若將是否需要使用侵入性氧氣治療將病患分為兩組,可以發現,收案時與輕症(不需要額外氧氣供應)及中度(需要低流量或非侵入性氧氣治療)患者相比,重症者(需要使用侵入性氧氣治療)的年齡層較高、男性的比例也較高,並有較高的比例同時伴隨有一些潛在疾病。兩組病患均大約於發病後第12天開始使用瑞德西韋;重症病患則大約於插管後2天開始用藥。

治療結果顯示:36人(68%)有看到臨床上供氧狀態的改善,包括插管接呼吸器的30人中有17例已可拔管、4名需要使用葉克膜的病患也有3人可以撤除。總計有25人(47%)出院,7人(13%)死亡。在插管使用呼吸器的重症患者中,死亡率為18%(6/34),不需要使用呼吸器的輕至中度患者死亡率為5%(1/19)。死亡的危險因子包括:年齡>70歲、收案時血清肌酸酐(creatinine)較高者。

藥物安全性方面,有32人(60%)有報告副作用,最多的是肝功能指數上升,腹瀉,紅疹,腎功能異常,低血壓。12人(23%)出現嚴重副作用,其中包括多重器官衰竭、敗血性休克、急性腎臟損傷和高血壓,但是無法難確認這些副作用是藥物本身還是病毒或是其他因素造成的。

結論是,接受瑞德西韋恩慈治療的患者臨床狀況,特別是對氧氣的需求,有68%得到改善;追蹤時間中位數為18天時的總死亡率為13%。

在另一個針對lopinavir-ritonavir療效進行的臨床試驗中,收案時199名病患僅有一名需要接受侵入性呼吸器治療,顯然絕大多數是屬於輕症的患者,而28天的總死亡率為22%。之前在中國的研究中,需要住進加護病房或是插管使用呼吸器的重症患者死亡率約為17-78%不等。因此作者認為本研究以中至重度病患為主的13%總死亡率應是很不錯的結果。

但是由於本研究報告是針對使用恩慈療法的新冠病患,因此有一些問題尚未能得到解答。例如:研究中沒有進行病毒量分析,所以無法證實瑞德西韋是否影響病毒量,進而改善病患的臨床狀況;少數病患因為使用藥物後症狀改善,因此並未完成完整的10天療程,但是無法確認是否能採用更短的療程(例如5天)即可達到治療效果。

顯然,最終療效的確認以及完整的副作用評估都需要等大型、完整的臨床試驗分析結果才能證實。

(財團法人國家衛生研究院 蔡齊嘉鈺醫師摘要整理)

BACKGROUND

Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2.

METHODS

We provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. This report is based on data from patients who received remdesivir during the period from January 25, 2020, through March 7, 2020, and have clinical data for at least 1 subsequent day.

RESULTS

Of the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed (including 7 patients with no post-treatment data and 1 with a dosing error). Of the 53 patients whose data were analyzed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation.

CONCLUSIONS

In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy. (Funded by Gilead Sciences.)

Author:Jonathan Grein, Norio Ohmagari, Daniel Shin,et al.
原文連結:https://www.nejm.org/doi/full/10.1056/NEJMoa2007016?query=featured_coronavirus