Rezafungin is an echinocandin approved in the US and EU to treat candidaemia and/or invasive candidiasis. This post-hoc, pooled analysis of the Phase 2 STRIVE and Phase 3 ReSTORE trials assessed rezafungin versus caspofungin in patients with candidaemia and/or invasive candidiasis (IC) in the intensive care unit (ICU) at randomisation. STRIVE and ReSTORE were randomised double-blind trials in adults with systemic signs and mycological confirmation of candidaemia and/or IC in blood or a normally sterile site ≤ 96 h before randomisation. Data were pooled for patients in the ICU at randomisation who received intravenous rezafungin (400 mg loading dose then 200 mg once weekly) or caspofungin (70 mg loading dose then 50 mg once daily) for ≤ 4 weeks. Outcomes were Day 30 all-cause mortality (primary outcome), Day 5 and 14 mycological eradication, time to negative blood culture, mortality attributable to candidaemia/invasive candidiasis, safety, and pharmacokinetics. Of 294 patients in STRIVE/ReSTORE, 113 were in the ICU at randomisation (rezafungin n = 46; caspofungin n = 67). At baseline, ~ 30% of patients in each group had impaired renal function and/or an Acute Physiologic Assessment and Chronic Health Evaluation II score ≥ 20. One patient (in the caspofungin group) was neutropenic at baseline. Day 30 all-cause mortality was 34.8% for rezafungin versus 25.4% for caspofungin. Day 5 and 14 mycological eradication was 78.3% and 71.7% for rezafungin versus 59.7% and 65.7% for caspofungin, respectively. Median time to negative blood culture was 18 (interquartile range, 12.6–43.0) versus 38 (interquartile range, 15.9–211.3) h for rezafungin versus caspofungin (stratified log-rank P = 0.001; nominal, not adjusted for multiplicity). Candidaemia/IC-attributable deaths occurred in two rezafungin patients versus one caspofungin patient. Safety profiles were similar between groups. Overall, 17.4% (rezafungin) versus 29.9% (caspofungin) of patients discontinued due to treatment-emergent adverse events. Rezafungin exposure following the initial 400-mg dose was comparable between patients in the ICU at randomisation (n = 50) and non-ICU patients (n = 117). Rezafungin was well tolerated and efficacious in critically ill, mainly non-neutropenic patients with candidaemia and/or IC. This analysis provides additional insights into the efficacy and safety of rezafungin in the ICU population.

中文翻译：

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瑞扎芬净与卡泊芬净治疗重症监护病房念珠菌血症或侵袭性念珠菌病患者：ReSTORE 和 STRIVE 随机试验的汇总分析


Rezafungin 是一种棘白菌素，在美国和欧盟获批用于治疗念珠菌血症和/或侵袭性念珠菌病。这项对 2 期 STRIVE 和 3 期 ReSTORE 试验的事后汇总分析在随机分组时评估了重症监护病房 （ICU） 中念珠菌血症和/或侵袭性念珠菌病 （IC） 患者的瑞扎芬净与卡泊芬净。STRIVE 和 ReSTORE 是在随机分组前 96 小时在有全身体征和真菌学确认的成人中进行的随机双盲试验，血液中或正常无菌部位≤念珠菌血症和/或 IC。对随机分组的 ICU 中接受静脉注射瑞扎芬净（400 mg 负荷剂量，然后 200 mg，每周一次）或卡泊芬净（70 mg 负荷剂量，然后 50 mg，每天一次）≤ 4 周的患者进行数据汇总。结局是第 30 天的全因死亡率 （主要结局） 、第 5 天和第 14 天的真菌根除、血培养阴性的时间、念珠菌血症/侵袭性念珠菌病导致的死亡率、安全性和药代动力学。在 STRIVE/ReSTORE 的 294 例患者中，113 例在随机分组时在 ICU 中 （rezafungin n = 46;卡泊芬净 n = 67）。在基线时，每组中 ~ 30% 的患者肾功能受损和/或急性生理评估和慢性健康评估 II 评分≥ 20。1 例患者 （卡泊芬净组） 基线时中性粒细胞减少。瑞扎芬净第 30 天的全因死亡率为 34.8%，卡泊芬净为 25.4%。第 5 天和第 14 天的真菌根除率分别为 rezafungin 的 78.3% 和 71.7%，而卡泊芬净分别为 59.7% 和 65.7%。血培养阴性的中位时间为 18 小时（四分位距，12.6-43.0），而瑞扎芬净与卡泊芬净为 38 小时（四分位距，15.9-211.3）小时（分层对数秩 P = 0.001;标称值，未调整多重性）。 2 例 rezafungin 患者与 1 例卡泊芬净患者发生念珠菌血症/IC 归因死亡。各组之间的安全性特征相似。总体而言，17.4% （rezafungin） 和 29.9% （caspofungin） 的患者因治疗中出现的不良事件而停药。随机分组时 ICU 患者 （n = 50） 和非 ICU 患者 （n = 117） 在初始 400 mg 剂量后服用 Rezafungin 暴露量相当。Rezafungin 在危重症患者中具有良好的耐受性和有效性，主要是非中性粒细胞减少的念珠菌血症和/或 IC。该分析为瑞扎芬净在 ICU 人群中的疗效和安全性提供了更多见解。