Rezafungin versus caspofungin for treatment of candidaemia and invasive candidiasis (ReSTORE): a multicentre, double-blind, double-dummy, randomised phase 3 trial
| العنوان: | Rezafungin versus caspofungin for treatment of candidaemia and invasive candidiasis (ReSTORE): a multicentre, double-blind, double-dummy, randomised phase 3 trial |
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| المؤلفون: | George R Thompson, Alex Soriano, Oliver A Cornely, Bart Jan Kullberg, Marin Kollef, Jose Vazquez, Patrick M Honore, Matteo Bassetti, John Pullman, Methee Chayakulkeeree, Ivan Poromanski, Cecilia Dignani, Anita F Das, Taylor Sandison, Peter G Pappas, Murat Akova, Rawan AlAgha, George Alangaden, Svenja J Albrecht, Barbara Alexander, Mohanad Al-Obaidi, German Ambasch, Fernando Armestar Rodriguez, Alpay Azap, Anthony Baffoe-Bonnie, Leila Belkhir, Ronen Ben-Ami, David Boutoille, Antonio Cascio, Louis YA Chai, Romanee Chaiwarith, Sharon Chen, Yee-Chun Chen, Yen-Hsu Chen, Jun Yong Choi, Young Hwa Choi, Darunee Chotiprasitsakul, Jin Won Chung, François Danion, Blandine Denis, Emilio Diaz Santos, Miguel O Dictar, Marc Diltoer, Herve Dupont, Sizhou Feng, Maria Angeles Ferre Colomer, Ricard Ferrer, Jean-Marie Fernand Roger Forel, Jesús Fortún-Abete, Julia Garcia-Diaz, Massimo Girardis, Fang He, Maya Hites, Mao-Wang Ho, Patrick Honore, Juan Pablo Horcajada Gallego, Haihui Huang, Po-Yen Huang, Yong Huang, Osamah Hussein, Poj Intalapaporn, Sutep Jaruratanasirikul, Luis Jauregui-Peredo, Misty Johnson, Dong Sik Jung, Kamonwan Jutivorakool, Winfried V Kern, Daniel H Kett, Thana Khawcharoenporn, Young Keun Kim, Philipp Koehler, Anastasia Kotanidou, Anne Lachiewicz, Qinhan Lin, Luis Eduardo Lopez Cortes, Hong Luo, Roberto Luzzati, Yasmin Maor, Todd McCarty, Maria Merelli, Paloma Merino Amador, John Midturi, Guglielmo Marco Migliorino, Jean-Paul Mira, Piroon Mootsikapun, Orla Morrissey, Patricia Munoz Garcia de Paredes, Cristina Mussini, Eleftherios Mylonakis, Saadalla Nseir, William Nseir, Zekaver Odabasi, Vasileios Papastamopoulos, David Paterson, Thomas F Patterson, Kyong Ran Peck, Zhiyong Peng, Nitipong Permpalung, Gaetan J Plantefeve, Ivan G Poromanski, Debra Powell, Mina Psichogiou, Ser Hon Puah, Galia Rahav, Antonio Ramos Martinez, Juan Carlos Ramos Ramos, Ayelet Raz-Pasteur, Carlos A Restrepo Castro, Fernando Riera, France Roblot, Regino Jose Rodriguez Alvarez, Benjamin Rogers, Emmanuel Roilides, Gregorio Sanchez Vallejo, Gabriele Sganga, Nikolaos Sipsas, Monica Slavin, Andrej Spec, Jacob Strahilevitz, Dora M Tancheva, Zhen Tao, Daniel Teschner, Eric Van Wijngaerden, Paschalis Vergidis, Pierluigi Viale, Fu-Der Wang, Shifu Wang, Gabriel Weber, Jianyu Weng, Jinfu Xu, Li Yao, Serap Yavuz, Mesut Yilmaz, Jo-Anne Young, Abel H Zarate, Jun Zeng, Yong Zhang |
| المساهمون: | UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/IREC/LTAP - Louvain Centre for Toxicology and Applied Pharmacology, UCL - (MGD) Services des soins intensifs, UCL - (SLuc) Service de médecine interne et maladies infectieuses (MIMI), Supporting clinical sciences, Intensive Care, Thompson G. R., Soriano A., Cornely O. A., Kullberg B. J., Kollef M., Vazquez J., Honore P. M., Bassetti M., Pullman J., Chayakulkeeree M., et al., UCL - (SLuc) Service de médecine interne générale |
| المصدر: | Lancet, Vol. 401, no. 10370, p. 49-59 (2023) The Lancet (London), 401, 49-59 The Lancet (London), 401, 10370, pp. 49-59 Lancet, p. [1-11] (2022) |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Pulmonary and Respiratory Medicine, Adult, Male, ReSTORE, General Medicine, invasive candidiasis, Middle Aged, infectious diseases, Critical Care and Intensive Care Medicine, Treatment, All institutes and research themes of the Radboud University Medical Center, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Treatment Outcome, Double-Blind Method, Caspofungin, candidaemia, Humans, Female, Administration, Intravenous, Candidiasis, Invasive, rezafungin |
| الوصف: | Item does not contain fulltext BACKGROUND: Rezafungin is a next-generation, once-a-week echinocandin in development for the treatment of candidaemia and invasive candidiasis and for the prevention of invasive fungal disease caused by Candida, Aspergillus, and Pneumocystis spp after blood and marrow transplantation. We aimed to compare the efficacy and safety of intravenous rezafungin versus intravenous caspofungin in patients with candidaemia and invasive candidiasis. METHODS: ReSTORE was a multicentre, double-blind, double-dummy, randomised phase 3 trial done at 66 tertiary care centres in 15 countries. Adults (≥18 years) with systemic signs and mycological confirmation of candidaemia or invasive candidiasis were eligible for inclusion and randomly assigned (1:1) to receive intravenous rezafungin once a week (400 mg in week 1, followed by 200 mg weekly, for a total of two to four doses) or intravenous caspofungin (70 mg loading dose on day 1, followed by 50 mg daily) for no more than 4 weeks. The primary endpoints were global cure (consisting of clinical cure, radiological cure, and mycological eradication) at day 14 for the European Medical Agency (EMA) and 30-day all-cause mortality for the US Food and Drug Administration (FDA), both with a target non-inferiority margin of 20%, assessed in the modified intention-to-treat population (all patients who received one or more doses of study drug and had documented Candida infection based on a culture from blood or another normally sterile site obtained within 96 h before randomisation). Safety was evaluated by the incidence and type of adverse events and deaths in the safety population, defined as all patients who received any amount of study drug. The trial is registered with ClinicalTrials.gov, NCT03667690, and is complete. FINDINGS: Between Oct 12, 2018, and Aug 29, 2021, 222 patients were screened for inclusion, and 199 patients (118 [59%] men; 81 [41%] women; mean age 61 years [SD 15·2]) were randomly assigned (100 [50%] patients to the rezafungin group and 99 [50%] patients to the caspofungin group). 55 (59%) of 93 patients in the rezafungin group and 57 (61%) of 94 patients in the caspofungin group had a global cure at day 14 (weighted treatment difference -1·1% [95% CI -14·9 to 12·7]; EMA primary endpoint). 22 (24%) of 93 patients in the rezafungin group and 20 (21%) of 94 patients in the caspofungin group died or had an unknown survival status at day 30 (treatment difference 2·4% [95% CI -9·7 to 14·4]; FDA primary endpoint). In the safety analysis, 89 (91%) of 98 patients in the rezafungin group and 83 (85%) of 98 patients in the caspofungin group had at least one treatment-emergent adverse event. The most common treatment-emergent adverse events that occurred in at least 5% of patients in either group were pyrexia, hypokalaemia, pneumonia, septic shock, and anaemia. 55 (56%) patients in the rezafungin group and 52 (53%) patients in the caspofungin group had serious adverse events. INTERPRETATION: Our data show that rezafungin was non-inferior to caspofungin for the primary endpoints of day-14 global cure (EMA) and 30-day all-cause mortality (FDA). Efficacy in the initial days of treatment warrants evaluation. There were no concerning trends in treatment-emergent or serious adverse events. These phase 3 results show the efficacy and safety of rezafungin and support its ongoing development. FUNDING: Cidara Therapeutics and Mundipharma. |
| وصف الملف: | application/pdf |
| تدمد: | 0140-6736 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d232fde8055f33c79f2f4b250c2a2249Test https://doi.org/10.1016/S0140-6736Test(22)02324-8 |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d232fde8055f33c79f2f4b250c2a2249 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 01406736 |
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