Division of Infectious Diseases, Department of Internal Medicine, and Department of Medical Microbiology and Immunology, University of California Davis Medical Center, Sacramento, CA, USA.
Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, CIBERINFEC, Barcelona, Spain.
Lancet Infect Dis. 2024 Mar;24(3):319-328. doi: 10.1016/S1473-3099(23)00551-0. Epub 2023 Nov 23.
Rezafungin, a new US Food and Drug Administration-approved, long-acting echinocandin to treat candidaemia and invasive candidiasis, was efficacious with a similar safety profile to caspofungin in clinical trials. We conducted pooled analyses of the phase 2 STRIVE and phase 3 ReSTORE rezafungin trials.
ReSTORE was a multicentre, double-blind, double-dummy, randomised phase 3 trial conducted at 66 tertiary care centres in 15 countries. STRIVE was a multicentre, double-blind, double-dummy, randomised phase 2 trial conducted at 44 centres in 10 countries. Adults (≥18 years) with candidaemia or invasive candidiasis were treated with once-a-week intravenous rezafungin (400 mg and 200 mg) or once-a-day intravenous caspofungin (70 mg and 50 mg). Efficacy was evaluated in a pooled modified intent-to-treat (mITT) population. Primary efficacy endpoint was day 30 all-cause mortality (tested for non-inferiority with a pre-specified margin of 20%). Secondary efficacy endpoint was mycological response. Safety was also evaluated. The STRIVE and ReSTORE trials are registered with ClinicalTrials.gov, NCT02734862 and NCT03667690, and both studies are complete.
ReSTORE was conducted from Oct 12, 2018, to Oct 11, 2021, and STRIVE from July 26, 2016, to April 18, 2019. The mITT population, pooling the data from the two trials, comprised 139 patients for rezafungin and 155 patients for caspofungin. Day 30 all-cause mortality rates were comparable between groups (19% [26 of 139] for the rezafungin group and 19% [30 of 155] for the caspofungin group) and the upper bound of the 95% CI for the weighted treatment difference was below 10% (-1·5% [95% CI -10·7 to 7·7]). Mycological eradication occurred by day 5 in 102 (73%) of 139 rezafungin patients and 100 (65%) of 155 caspofungin patients (weighted treatment difference 10·0% [95% CI -0·3 to 20·4]). Safety profiles were similar across groups.
Rezafungin was non-inferior to caspofungin for all-cause mortality, with a potential early treatment benefit, possibly reflecting rezafungin's front-loaded dosing regimen. These findings are of clinical importance in fighting active and aggressive infections and reducing the morbidity and mortality caused by candidaemia and invasive candidiasis.
Melinta Therapeutics and Cidara Therapeutics.
雷沙氟康唑是一种新的获得美国食品药品监督管理局批准的长效棘白菌素类药物，用于治疗念珠菌血症和侵袭性念珠菌病，在临床试验中与卡泊芬净具有相似的疗效和安全性。我们对 2 期 STRIVE 研究和 3 期 ReSTORE 研究进行了汇总分析。
ReSTORE 是一项在 15 个国家的 66 个三级护理中心进行的多中心、双盲、双模拟、随机 3 期临床试验。STRIVE 是一项在 10 个国家的 44 个中心进行的多中心、双盲、双模拟、随机 2 期临床试验。患有念珠菌血症或侵袭性念珠菌病的成年人（≥18 岁）接受每周一次静脉注射雷沙氟康唑（400mg 和 200mg）或每天一次静脉注射卡泊芬净（70mg 和 50mg）治疗。在修改后的意向治疗（mITT）人群中评估疗效。主要疗效终点为第 30 天全因死亡率（使用预先指定的 20%的非劣效性边界进行检验）。次要疗效终点为真菌学应答。同时还评估了安全性。STRIVE 和 ReSTORE 试验均在 ClinicalTrials.gov 上注册，NCT02734862 和 NCT03667690，两项研究均已完成。
ReSTORE 研究于 2018 年 10 月 12 日至 2021 年 10 月 11 日进行，STRIVE 研究于 2016 年 7 月 26 日至 2019 年 4 月 18 日进行。mITT 人群，即两项试验数据的汇总人群，包括雷沙氟康唑组 139 例和卡泊芬净组 155 例。第 30 天全因死亡率在两组间相当（雷沙氟康唑组为 19%[139 例中的 26 例]，卡泊芬净组为 19%[155 例中的 30 例]），加权治疗差异的 95%置信区间上限低于 10%（-1.5%[95%置信区间-10.7 至 7.7]）。雷沙氟康唑组有 102（73%）例患者在第 5 天真菌学清除，卡泊芬净组有 100（65%）例患者，加权治疗差异为 10.0%（95%置信区间 0.3 至 20.4）。两组的安全性特征相似。
雷沙氟康唑在全因死亡率方面不劣于卡泊芬净，且可能具有早期治疗获益，这可能反映了雷沙氟康唑的负荷剂量给药方案。这些发现对于治疗活跃和侵袭性感染以及降低念珠菌血症和侵袭性念珠菌病引起的发病率和死亡率具有重要的临床意义。
Melinta Therapeutics 和 Cidara Therapeutics。
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