ICU Department, CHU UCL Godinne Namur, UCL Louvain Medical School, Namur, Belgium.
Department of Anaesthesiology and Intensive Care, University of Modena and Reggio Emilia and University Hospital of Modena, Largo del Pozzo, Modena, Italy.
Crit Care. 2024 Oct 28;28(1):348. doi: 10.1186/s13054-024-05117-5.
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.
瑞他康唑是一种棘白菌素类药物，已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。本项针对 2 期 STRIVE 研究和 3 期 ReSTORE 研究的事后分析评估了瑞他康唑与卡泊芬净在念珠菌血症和/或侵袭性念珠菌病（ICU）患者中的疗效，这些患者在随机分组时处于 ICU 中。
STRIVE 和 ReSTORE 是两项随机双盲研究，纳入了在随机分组前 96 小时内有系统症状和血液或正常无菌部位的念珠菌血症和/或 IC 的微生物学证据的成年患者。对随机分组时处于 ICU 中的接受静脉滴注瑞他康唑（400mg 负荷剂量，然后每周一次 200mg）或卡泊芬净（70mg 负荷剂量，然后每天一次 50mg）治疗不超过 4 周的患者进行数据汇总。主要结局为第 30 天全因死亡率（首要结局）、第 5 天和第 14 天的真菌学清除率、血培养转为阴性的时间、念珠菌血症/侵袭性念珠菌病相关死亡率、安全性和药代动力学。
在 STRIVE/ReSTORE 研究的 294 例患者中，有 113 例在随机分组时处于 ICU（瑞他康唑组 n=46；卡泊芬净组 n=67）。在基线时，每组约 30%的患者存在肾功能损害和/或急性生理与慢性健康状况评分 II 评分≥20。1 例患者（卡泊芬净组）在基线时中性粒细胞减少。瑞他康唑组第 30 天的全因死亡率为 34.8%，卡泊芬净组为 25.4%。瑞他康唑组第 5 天和第 14 天的真菌学清除率分别为 78.3%和 71.7%，卡泊芬净组分别为 59.7%和 65.7%。瑞他康唑组和卡泊芬净组血培养转为阴性的中位时间分别为 18（四分位间距，12.6-43.0）和 38（四分位间距，15.9-211.3）小时（分层对数秩检验 P=0.001；名义检验，未校正多重性）。瑞他康唑组有 2 例患者发生念珠菌血症/侵袭性念珠菌病相关死亡，卡泊芬净组有 1 例患者发生该事件。两组的安全性特征相似。总体而言，17.4%（瑞他康唑）和 29.9%（卡泊芬净）的患者因治疗出现的不良事件而停药。在随机分组时处于 ICU 的患者（n=50）和非 ICU 患者（n=117）中，瑞他康唑在初始 400mg 剂量后的暴露情况相似。
瑞他康唑在主要为非中性粒细胞减少的重症、血流感染和/或侵袭性念珠菌病患者中耐受良好，疗效确切。本分析为瑞他康唑在 ICU 人群中的疗效和安全性提供了更多的见解。
