Tomita Noriko, Saito Sho, Terada-Hirashima Junko, Mikami Ayako, Uemura Yukari, Kutsuna Satoshi, Nomoto Hidetoshi, Fujisawa Kyoko, Nagashima Maki, Terada Mari, Ashida Shinobu, Morioka Shinichiro, Satake Masahiro, Hangaishi Akira, Togano Tomiteru, Shiratori Katsuyuki, Takamatsu Yuki, Maeda Kenji, Ohmagari Norio, Sugiura Wataru, Mitsuya Hiroaki
Center for Clinical Sciences, Center Hospital of the National Center for Global Health and Medicine, Tokyo 162-8655, Japan.
Disease Control and Prevention Center, Center Hospital of the National Center for Global Health and Medicine, Tokyo 162-8655, Japan.
Life (Basel). 2022 Jun 8;12(6):856. doi: 10.3390/life12060856.
Coronavirus disease 2019 is a global public health concern. As of December 2020, the therapeutic agents approved for coronavirus disease 2019 in Japan were limited to two drugs: remdesivir, an antiviral drug, granted a Special Approval for Emergency on 7 May 2020, and dexamethasone, which has an anti-inflammatory effect. The aim of this study is to evaluate the efficacy of convalescent plasma collected from donors who recovered from coronavirus disease 2019.
This is an open-label, randomized controlled trial comprising two groups: a convalescent plasma and a standard-of-care group. Plasma administered to patients with coronavirus disease 2019 randomized in the convalescent plasma group of this trial will be plasma that has been collected and stored in an associated study. Patients with a diagnosis of mild coronavirus disease 2019 will be included in this trial. The efficacy of convalescent plasma transfusion will be evaluated by comparing the convalescent plasma group to the standard-of-care group (without convalescent plasma transfusion) with respect to changes in the viral load and other measures. The primary endpoint will be time-weighted average changes in the SARS-CoV-2 virus load in nasopharyngeal swabs from day 0 to days 3 and 5. It is hypothesized that the intervention should result in a decrease in the viral load in the convalescent plasma group until day 5. This endpoint has been used as a change in viral load has and been used as an index of therapeutic effect in several previous studies.
The proposed trial has the potential to prevent patients with mild COVID-19 from developing a more severe illness. Several RCTs of convalescent plasma therapy have already been conducted in countries outside of Japan, but no conclusion has been reached with respect to the efficacy of convalescent plasma therapy, which is likely in part because of the heterogeneity of the types of target patients, interventions, and endpoints among trials. Actually, previous clinical trials on plasma therapy have shown inconsistent efficacy and are sometimes ineffective in COVID-19 patients with severe disease, which is due to unmeasured neutralizing antibody titer in the COVID-19 convalescent plasma. To improve this issue, in this study, we measure neutralizing activity of convalescent plasma before administration and provide the plasma with high neutralizing activity to the subjects. It is hoped that this study will further evidence to support the role of convalescent plasma therapy in COVID-19.
2019冠状病毒病是一个全球公共卫生问题。截至2020年12月，在日本被批准用于治疗2019冠状病毒病的治疗药物仅限于两种：抗病毒药物瑞德西韦，于2020年5月7日获得紧急特别批准；以及具有抗炎作用的地塞米松。本研究的目的是评估从2019冠状病毒病康复的供体采集的恢复期血浆的疗效。
这是一项开放标签的随机对照试验，包括两组：恢复期血浆组和标准治疗组。在本试验的恢复期血浆组中随机分配给2019冠状病毒病患者的血浆将是在一项相关研究中采集和储存的血浆。确诊为轻度2019冠状病毒病的患者将纳入本试验。通过比较恢复期血浆组和标准治疗组（不进行恢复期血浆输注）在病毒载量和其他指标方面的变化，评估恢复期血浆输注的疗效。主要终点将是从第0天到第3天和第5天鼻咽拭子中SARS-CoV-2病毒载量的时间加权平均变化。假设干预措施应导致恢复期血浆组的病毒载量在第5天之前下降。这个终点已被用作病毒载量的变化，并在之前的几项研究中被用作治疗效果的指标。
拟进行的试验有可能防止轻度COVID-19患者病情加重。在日本以外的国家已经进行了几项恢复期血浆疗法的随机对照试验，但关于恢复期血浆疗法的疗效尚未得出结论，这可能部分是由于试验中目标患者类型、干预措施和终点的异质性。实际上，先前关于血浆疗法的临床试验显示疗效不一致，有时对重症COVID-19患者无效，这是由于COVID-19恢复期血浆中未检测到的中和抗体滴度所致。为改善这一问题，在本研究中，我们在给药前测量恢复期血浆的中和活性，并将具有高中和活性的血浆提供给受试者。希望本研究将进一步提供证据支持恢复期血浆疗法在COVID-19中的作用。
