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：免疫调节疗法已在重症新型冠状病毒肺炎（COVID-19）患者中展现出有益疗效。合并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（去甲肾上腺素剂量≥0.2 μg/kg/min以维持平均动脉压≥65 mmHg）、白细胞介素-6（interleukin-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组采用CytoSorb®吸附器进行治疗，疗程最长可达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（去甲肾上腺素剂量≤0.05 μg/kg/min且持续≥24小时）。
结果：本研究共筛查242例患者，最终24例被随机分组，其中HT组12例，SMT组12例。两组患者的基线疾病严重程度相当：简化急性生理学评分II（SAPS II）中位数分别为75分（HT组）与79分（SMT组，p=0.590）；序贯器官衰竭评分（SOFA）分别为17分与16分（p=0.551）。HT组与SMT组的基线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组达到休克缓解（即主要终点）的比例分别为33%（4/12）与17%（2/12，p=0.640）。HT组28天死亡率为58%（7/12），SMT组为67%（8/12，p=1.0）。在5天的治疗期内，SMT组有6/12（50%）患者死亡，而HT组仅1/12（8%）患者死亡。
结论：HT在干预周期内展现出临床改善的非显著性趋势。针对筛选出的特定患者，HT或可作为转运前及后续治疗决策前的病情稳定方案。该研究结果尚需开展更大规模的临床试验进一步验证。