Department of Anesthesiology, Critical Care, Emergency and Pain Medicine, Wuerzburg University Hospital, Wuerzburg, Germany.
Vascular Biology Center, Department of Pharmacology and Toxicology and Division of Pulmonary and Critical Care Medicine, Medical College of Georgia at Augusta University, Augusta, GA, 30912, USA.
Trials. 2022 Apr 4;23(1):252. doi: 10.1186/s13063-022-06182-3.
In May 2018, the first patient was enrolled in the phase-IIb clinical trial "Safety and Preliminary Efficacy of Sequential Multiple Ascending Doses of Solnatide to Treat Pulmonary Permeability Edema in Patients with Moderate to Severe ARDS." With the onset of the COVID-19 pandemic in early 2020, the continuation and successful execution of this clinical study was in danger. Therefore, before the Data Safety Monitoring Board (DSMB) allowed proceeding with the study and enrollment of further COVID-19 ARDS patients into it, additional assessment on possible study bias was considered mandatory.
We conducted an ad hoc interim analysis of 16 patients (5 COVID-19- ARDS patients and 11 with ARDS from different causes) from the phase-IIB clinical trial. We assessed possible differences in clinical characteristics of the ARDS patients and the impact of the pandemic on study execution.
COVID-19 patients seemed to be less sick at baseline, which also showed in higher survival rates over the 28-day observation period. Trial specific outcomes regarding pulmonary edema and ventilation parameters did not differ between the groups, nor did more general indicators of (pulmonary) sepsis like oxygenation ratio and required noradrenaline doses.
The DSMB and the investigators did not find any evidence that patients suffering from ARDS due to SARS-CoV-2 may be at higher (or generally altered) risk when included in the trial, nor were there indications that those patients might influence the integrity of the study data altogether. For this reason, a continuation of the phase IIB clinical study activities can be justified. Researchers continuing clinical trials during the pandemic should always be aware that the exceptional circumstances may alter study results and therefore adaptations of the study design might be necessary.
2018 年 5 月，首位患者入组了“序贯递增剂量索那肽治疗中重度 ARDS 患者肺通透性水肿的安全性和初步疗效”的 IIb 期临床试验。随着 2020 年初 COVID-19 大流行的爆发，该临床研究的继续和成功实施面临危险。因此，在数据安全监测委员会（DSMB）允许继续进行研究并招募更多 COVID-19 ARDS 患者入组之前，认为有必要对可能存在的研究偏倚进行额外评估。
我们对来自 IIb 期临床试验的 16 例患者（5 例 COVID-19-ARDS 患者和 11 例来自不同病因的 ARDS 患者）进行了一项特别的中期分析。我们评估了 ARDS 患者的临床特征差异以及大流行对研究实施的影响。
COVID-19 患者在基线时似乎病情较轻，这也体现在 28 天观察期内的生存率较高。两组患者在肺水肿和通气参数方面的试验特定结局无差异，一般（肺部）脓毒症的指标如氧合比和所需去甲肾上腺素剂量也无差异。
DSMB 和研究者未发现任何证据表明，因 SARS-CoV-2 而患有 ARDS 的患者在入组试验时可能面临更高（或普遍改变）的风险，也没有迹象表明这些患者可能会影响整个研究数据的完整性。因此，可以证明继续进行 IIb 期临床研究活动是合理的。在大流行期间继续进行临床试验的研究人员应始终意识到，特殊情况可能会改变研究结果，因此可能需要调整研究设计。
