Supplementary Material for: Effect of Hemadsorption Therapy in Critically Ill Patients with COVID-19 (CYTOCOV-19): A Prospective Randomized Controlled Pilot Trial

Introduction: Immunomodulatory therapies have shown beneficial effects in patients with severe COVID-19. Patients with hypercytokinemia might benefit from the removal of inflammatory mediators via hemadsorption. Methods: Single-center prospective randomized trial at the University Medical Center Hamburg-Eppendorf (Germany). Patients with confirmed COVID-19, refractory shock (norepinephrine ≥0.2 µg/kg/min to maintain a mean arterial pressure ≥65 mm Hg), interleukin-6 (IL-6) ≥500 ng/L, and an indication for renal replacement therapy or extracorporeal membrane oxygenation were included. Patients received either hemadsorption therapy (HT) or standard medical therapy (SMT). For HT, a CytoSorb® adsorber was used for up to 5 days and was replaced every 18–24 h. The primary endpoint was sustained hemodynamic improvement (norepinephrine ≤0.05 µg/kg/min ≥24 h). Results: Of 242 screened patients, 24 were randomized and assigned to either HT (N = 12) or SMT (N = 12). Both groups had similar severity as assessed by SAPS II (median 75 points HT group vs. 79 SMT group, p = 0.590) and SOFA (17 vs. 16, p = 0.551). Median IL-6 levels were 2,269 (IQR 948–3,679) and 3,747 (1,301–5,415) ng/L in the HT and SMT groups at baseline, respectively (p = 0.378). Shock resolution (primary endpoint) was reached in 33% (4/12) versus 17% (2/12) in the HT and SMT groups, respectively (p = 0.640). Twenty-eight-day mortality was 58% (7/12) in the HT compared to 67% (8/12) in the SMT group (p = 1.0). During the treatment period of 5 days, 6/12 (50%) of the SMT patients died, in contrast to 1/12 (8%) in the HT group. Conclusion: HT was associated with a non-significant trend toward clinical improvement within the intervention period. In selected patients, HT might be an option for stabilization before transfer and further therapeutic decisions. This finding warrants further investigation in larger trials.引言：免疫调节疗法在重症新型冠状病毒肺炎（COVID-19）患者中已展现出有益疗效。伴细胞因子血症的患者或可通过血液吸附清除炎症介质而获益。 方法：本研究为德国汉堡-埃彭多夫大学医学中心开展的单中心前瞻性随机对照试验。纳入经确诊的COVID-19、难治性休克（去甲肾上腺素用量≥0.2 μg/kg/min以维持平均动脉压≥65 mmHg）、白细胞介素-6（IL-6）≥500 ng/L，且具备肾脏替代治疗或体外膜肺氧合指征的患者。患者被随机分配至血液吸附治疗（hemadsorption therapy, HT）组或标准药物治疗（standard medical therapy, SMT）组。HT组使用CytoSorb®吸附器进行治疗，疗程最长5天，每18~24小时更换一次吸附器。本研究的主要终点为血流动力学持续改善（去甲肾上腺素用量≤0.05 μg/kg/min且持续≥24小时）。 结果：共筛查242例患者，最终24例被随机分组，其中HT组12例，SMT组12例。两组患者的疾病严重程度经简化急性生理学评分II（SAPS II）与序贯器官衰竭评分（SOFA）评估后无显著差异：SAPS II评分中位数HT组为75分，SMT组为79分（p=0.590）；SOFA评分中位数HT组为17分，SMT组为16分（p=0.551）。基线时HT组与SMT组的IL-6水平中位数分别为2269（四分位距948~3679）ng/L与3747（1301~5415）ng/L（p=0.378）。HT组与SMT组的休克缓解（即本研究主要终点）达标率分别为33%（4/12）与17%（2/12），组间差异无统计学意义（p=0.640）。HT组28天死亡率为58%（7/12），SMT组为67%（8/12），组间无显著差异（p=1.0）。在5天的治疗期内，SMT组有6/12（50%）的患者死亡，而HT组仅1/12（8%）的患者死亡。 结论：在干预期内，血液吸附治疗呈现出临床改善的非显著性趋势。对于经筛选的特定患者人群，HT或可作为转运前病情稳定及后续治疗决策前的可选方案。该研究发现仍需在更大规模的临床试验中开展进一步验证。