George R Thompson, Haihui Huang, Sizhou Feng, Yunsong Yu, Alex Soriano, Oliver A Cornely, Bart Jan Kullberg, Peter G Pappas, Marin Kollef, Jose A Vazquez, Patrick M Honore, Laura Cox, Matteo Bassetti
{"title":"Rezafungin与Caspofungin治疗念珠菌病和侵袭性念珠菌病:来自双盲、随机、3期恢复试验(包括中国扩展研究)的结果","authors":"George R Thompson, Haihui Huang, Sizhou Feng, Yunsong Yu, Alex Soriano, Oliver A Cornely, Bart Jan Kullberg, Peter G Pappas, Marin Kollef, Jose A Vazquez, Patrick M Honore, Laura Cox, Matteo Bassetti","doi":"10.1093/ofid/ofaf555","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Rezafungin is approved for use in adults with candidemia and/or invasive candidiasis (IC) based on data from the ReSTORE trial (NCT03667690), which demonstrated noninferior efficacy to caspofungin. For regulatory purposes, an additional cohort of patients from China was recruited to ReSTORE. Here, we compared rezafungin and caspofungin in patients with candidemia and/or IC through analysis of the ReSTORE global data plus the China extension study.</p><p><strong>Methods: </strong>Adults with candidemia/IC were randomized (1:1) to receive weekly rezafungin (400/200 mg) or daily caspofungin (70/50 mg) for ≤28 days. Noninferiority was concluded for primary efficacy endpoints if the upper bound of the 95% confidence interval (CI) was below 20% for Day 30 all-cause mortality and if the weighted lower bound was above -20% for Day 14 global cure. Additional efficacy outcomes and safety were evaluated.</p><p><strong>Results: </strong>Overall, 246 patients were randomized (122 rezafungin and 124 caspofungin). Noninferiority was demonstrated for both primary endpoints. Day 30 all-cause mortality was 25.2% and 24.8% (treatment difference 0.4%; 95% CI -10.8, 11.6) and Day 14 global cure was 56.5% and 57.3% (weighted treatment difference -1.0%; 95% CI -13.5, 11.6) with rezafungin versus caspofungin, respectively. Day 5 mycological eradication was numerically higher (68.7% vs 63.2%) and time to negative blood culture was numerically shorter (median 26.5 vs 38.8 h). Safety was comparable between groups; 53.3% (64/120; rezafungin) and 53.7% (66/123; caspofungin) of patients experienced serious adverse events.</p><p><strong>Conclusions: </strong>This analysis confirmed the overall efficacy and safety of rezafungin demonstrated in ReSTORE, with early efficacy related to front-loaded exposure.</p>","PeriodicalId":19517,"journal":{"name":"Open Forum Infectious Diseases","volume":"12 9","pages":"ofaf555"},"PeriodicalIF":3.8000,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12461853/pdf/","citationCount":"0","resultStr":"{\"title\":\"Rezafungin Versus Caspofungin for the Treatment of Candidemia and Invasive Candidiasis: Results from the Double-blind, Randomized, Phase 3 ReSTORE Trial Including the China Extension Study.\",\"authors\":\"George R Thompson, Haihui Huang, Sizhou Feng, Yunsong Yu, Alex Soriano, Oliver A Cornely, Bart Jan Kullberg, Peter G Pappas, Marin Kollef, Jose A Vazquez, Patrick M Honore, Laura Cox, Matteo Bassetti\",\"doi\":\"10.1093/ofid/ofaf555\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Rezafungin is approved for use in adults with candidemia and/or invasive candidiasis (IC) based on data from the ReSTORE trial (NCT03667690), which demonstrated noninferior efficacy to caspofungin. For regulatory purposes, an additional cohort of patients from China was recruited to ReSTORE. Here, we compared rezafungin and caspofungin in patients with candidemia and/or IC through analysis of the ReSTORE global data plus the China extension study.</p><p><strong>Methods: </strong>Adults with candidemia/IC were randomized (1:1) to receive weekly rezafungin (400/200 mg) or daily caspofungin (70/50 mg) for ≤28 days. Noninferiority was concluded for primary efficacy endpoints if the upper bound of the 95% confidence interval (CI) was below 20% for Day 30 all-cause mortality and if the weighted lower bound was above -20% for Day 14 global cure. Additional efficacy outcomes and safety were evaluated.</p><p><strong>Results: </strong>Overall, 246 patients were randomized (122 rezafungin and 124 caspofungin). Noninferiority was demonstrated for both primary endpoints. Day 30 all-cause mortality was 25.2% and 24.8% (treatment difference 0.4%; 95% CI -10.8, 11.6) and Day 14 global cure was 56.5% and 57.3% (weighted treatment difference -1.0%; 95% CI -13.5, 11.6) with rezafungin versus caspofungin, respectively. Day 5 mycological eradication was numerically higher (68.7% vs 63.2%) and time to negative blood culture was numerically shorter (median 26.5 vs 38.8 h). Safety was comparable between groups; 53.3% (64/120; rezafungin) and 53.7% (66/123; caspofungin) of patients experienced serious adverse events.</p><p><strong>Conclusions: </strong>This analysis confirmed the overall efficacy and safety of rezafungin demonstrated in ReSTORE, with early efficacy related to front-loaded exposure.</p>\",\"PeriodicalId\":19517,\"journal\":{\"name\":\"Open Forum Infectious Diseases\",\"volume\":\"12 9\",\"pages\":\"ofaf555\"},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2025-09-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12461853/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Open Forum Infectious Diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/ofid/ofaf555\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/9/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Open Forum Infectious Diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/ofid/ofaf555","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/9/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景:基于ReSTORE试验(NCT03667690)的数据,Rezafungin被批准用于成人念珠菌病和/或侵袭性念珠菌病(IC),该试验证明其疗效优于caspofungin。出于监管目的,从中国额外招募了一批患者进行ReSTORE研究。在这里,我们通过对ReSTORE全球数据和中国扩展研究的分析,比较了rezafungin和caspofungin在念珠菌血症和/或IC患者中的作用。方法:成人念珠菌病/IC患者随机(1:1)接受每周rezafungin (400/200 mg)或每日caspofungin (70/50 mg)治疗≤28天。如果第30天全因死亡率95%置信区间(CI)的上界低于20%,第14天全治愈的加权下界高于-20%,则主要疗效终点的非劣效性被认定。对其他疗效、结果和安全性进行了评估。结果:总的来说,246名患者被随机分配(122名rezafungin和124名caspofungin)。两个主要终点均无劣效性。第30天,rezafungin与caspofungin的全因死亡率分别为25.2%和24.8%(治疗差异0.4%;95% CI -10.8, 11.6),第14天的总治愈率分别为56.5%和57.3%(加权治疗差异-1.0%;95% CI -13.5, 11.6)。第5天的真菌学根除率较高(68.7% vs 63.2%),到阴性血培养的时间较短(中位数26.5 h vs 38.8 h)。安全性组间具有可比性;53.3% (64/120; rezafungin)和53.7% (66/123;caspofungin)的患者出现严重不良事件。结论:该分析证实了rezafungin在ReSTORE中显示的总体疗效和安全性,早期疗效与前负荷暴露有关。
Rezafungin Versus Caspofungin for the Treatment of Candidemia and Invasive Candidiasis: Results from the Double-blind, Randomized, Phase 3 ReSTORE Trial Including the China Extension Study.
Background: Rezafungin is approved for use in adults with candidemia and/or invasive candidiasis (IC) based on data from the ReSTORE trial (NCT03667690), which demonstrated noninferior efficacy to caspofungin. For regulatory purposes, an additional cohort of patients from China was recruited to ReSTORE. Here, we compared rezafungin and caspofungin in patients with candidemia and/or IC through analysis of the ReSTORE global data plus the China extension study.
Methods: Adults with candidemia/IC were randomized (1:1) to receive weekly rezafungin (400/200 mg) or daily caspofungin (70/50 mg) for ≤28 days. Noninferiority was concluded for primary efficacy endpoints if the upper bound of the 95% confidence interval (CI) was below 20% for Day 30 all-cause mortality and if the weighted lower bound was above -20% for Day 14 global cure. Additional efficacy outcomes and safety were evaluated.
Results: Overall, 246 patients were randomized (122 rezafungin and 124 caspofungin). Noninferiority was demonstrated for both primary endpoints. Day 30 all-cause mortality was 25.2% and 24.8% (treatment difference 0.4%; 95% CI -10.8, 11.6) and Day 14 global cure was 56.5% and 57.3% (weighted treatment difference -1.0%; 95% CI -13.5, 11.6) with rezafungin versus caspofungin, respectively. Day 5 mycological eradication was numerically higher (68.7% vs 63.2%) and time to negative blood culture was numerically shorter (median 26.5 vs 38.8 h). Safety was comparable between groups; 53.3% (64/120; rezafungin) and 53.7% (66/123; caspofungin) of patients experienced serious adverse events.
Conclusions: This analysis confirmed the overall efficacy and safety of rezafungin demonstrated in ReSTORE, with early efficacy related to front-loaded exposure.
期刊介绍:
Open Forum Infectious Diseases provides a global forum for the publication of clinical, translational, and basic research findings in a fully open access, online journal environment. The journal reflects the broad diversity of the field of infectious diseases, and focuses on the intersection of biomedical science and clinical practice, with a particular emphasis on knowledge that holds the potential to improve patient care in populations around the world. Fully peer-reviewed, OFID supports the international community of infectious diseases experts by providing a venue for articles that further the understanding of all aspects of infectious diseases.