Study protocol: A randomized, double-blind, placebo-controlled trial of isavuconazole prophylaxis for the prevention of covid-19-associated pulmonary aspergillosis

IF 1.4 Q4 MEDICINE, RESEARCH & EXPERIMENTAL Contemporary Clinical Trials Communications Pub Date : 2024-05-17 DOI:10.1016/j.conctc.2024.101310
Jeffrey D. Jenks , Martin Hoenigl , George R. Thompson 3rd
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Abstract

Background

During the early stages of the coronavirus disease 2019 (COVID-19) pandemic, those with severe COVID-19 infection were at risk for a number of opportunistic infections including COVID-19-associated pulmonary aspergillosis (CAPA). We initiated a randomized clinical trial to evaluate whether isavuconazole, a triazole antifungal, could prevent CAPA and improve survival in patients admitted to the ICU with severe COVID-19 infection.

Methods

We designed a phase III/IV randomized, double-blind, two-arm, placebo-controlled trial evaluating standard of care (SOC) plus isavuconazole versus SOC plus placebo and were to enroll participants admitted to the ICU with severe COVID-19 infection at three medical centers in California, United States. The projected sample size was 162 participants.

Results

Due to poor enrollment and the declining number of COVID-19 cases over time, the study was terminated after 7 participants were enrolled, all enrolled at one study site (UC San Diego Health). CAPA was suspected in two participants and they were started on open-label isavuconazole. One was withdrawn due to possible isavuconazole-related adverse side effects.

Conclusion

Enrollment was slower-than-expected due to multiple factors, including competing COVID-19-related studies and hesitancy from potential study participants or their families to join the study. Our experience highlights some of the difficulties in planning and running a clinical trial focused on fungal superinfections involving severely ill patients during the height of the COVID-19 pandemic. Lessons learned from this study will help in the design of proposed studies examining antifungal prophylaxis against aspergillosis following other severe respiratory viral infections.

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研究方案:伊沙武康唑预防性治疗与柯维-19相关肺曲霉菌病的随机、双盲、安慰剂对照试验
背景在2019年冠状病毒病(COVID-19)大流行的早期阶段,COVID-19严重感染者有可能患上包括COVID-19相关肺曲霉菌病(CAPA)在内的多种机会性感染。我们发起了一项随机临床试验,以评估三唑类抗真菌药异武康唑是否能预防CAPA并提高重症监护病房重症COVID-19感染患者的存活率。我们设计了一项III/IV期随机、双盲、双臂、安慰剂对照试验,评估标准护理(SOC)加异武康唑与SOC加安慰剂的效果,并在美国加利福尼亚州的三家医疗中心招募重症COVID-19感染重症监护病房的患者。结果由于入组情况不佳以及随着时间推移 COVID-19 病例数量不断减少,该研究在入组 7 名参与者后终止,所有参与者均在一个研究地点(加州大学圣地亚哥分校医疗中心)入组。两名参与者被怀疑感染了CAPA,他们开始接受开放标签的异武康唑治疗。结论由于多种因素,包括与 COVID-19 相关的竞争研究以及潜在研究参与者或其家人对加入研究犹豫不决,因此研究的注册速度低于预期。我们的经验凸显了在 COVID-19 大流行期间规划和开展一项以真菌超级感染为重点、涉及重症患者的临床试验所面临的一些困难。从这项研究中汲取的经验教训将有助于设计拟议中的研究,对其他严重呼吸道病毒感染后的曲霉菌病进行抗真菌预防。
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来源期刊
Contemporary Clinical Trials Communications
Contemporary Clinical Trials Communications Pharmacology, Toxicology and Pharmaceutics-Pharmacology
CiteScore
2.70
自引率
6.70%
发文量
146
审稿时长
20 weeks
期刊介绍: Contemporary Clinical Trials Communications is an international peer reviewed open access journal that publishes articles pertaining to all aspects of clinical trials, including, but not limited to, design, conduct, analysis, regulation and ethics. Manuscripts submitted should appeal to a readership drawn from a wide range of disciplines including medicine, life science, pharmaceutical science, biostatistics, epidemiology, computer science, management science, behavioral science, and bioethics. Contemporary Clinical Trials Communications is unique in that it is outside the confines of disease specifications, and it strives to increase the transparency of medical research and reduce publication bias by publishing scientifically valid original research findings irrespective of their perceived importance, significance or impact. Both randomized and non-randomized trials are within the scope of the Journal. Some common topics include trial design rationale and methods, operational methodologies and challenges, and positive and negative trial results. In addition to original research, the Journal also welcomes other types of communications including, but are not limited to, methodology reviews, perspectives and discussions. Through timely dissemination of advances in clinical trials, the goal of Contemporary Clinical Trials Communications is to serve as a platform to enhance the communication and collaboration within the global clinical trials community that ultimately advances this field of research for the benefit of patients.
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