Raoul Herbrecht1, Thomas F Patterson2, Monica A Slavin3, Oscar Marchetti4, Johan Maertens5, Elizabeth M Johnson6, Haran T Schlamm7, J Peter Donnelly8, Peter G Pappas9. 1. Department of Oncology and Hematology, Hôpital de Hautepierre and Université de Strasbourg, France. 2. University of Texas Health Science Center and South Texas Veterans Health Care System, San Antonio. 3. Peter MacCallum Cancer Center and University of Melbourne, Australia. 4. Infectious Diseases Service, Department of Medicine, Lausanne University Hospital (CHUV), Switzerland. 5. Universitaire Ziekenhuizen Leuven, Campus Gasthuisberg, KU Leuven, Belgium. 6. Public Health England Mycology Reference Laboratory and National Collection of Pathogenic Fungi, Bristol, United Kingdom. 7. Pfizer Global Research and Development, New York, New York. 8. Radboud University Medical Center, Nijmegen, The Netherlands. 9. Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham.
Abstract
BACKGROUND: Strict definition of invasive aspergillosis (IA) cases is required to allow precise conclusions about the efficacy of antifungal therapy. The Global Comparative Aspergillus Study (GCAS) compared voriconazole to amphotericin B (AmB) deoxycholate for the primary therapy of IA. Because predefined definitions used for this trial were substantially different from the consensus definitions proposed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group in 2008, we recategorized the 379 episodes of the GCAS according to the later definitions. METHODS: The objectives were to assess the impact of the current definitions on the classification of the episodes and to provide comparative efficacy for probable/proven and possible IA in patients treated with either voriconazole or AmB. In addition to original data, we integrated the results of baseline galactomannan serum levels obtained from 249 (65.7%) frozen samples. The original response assessment was accepted unchanged. RESULTS: Recategorization allowed 59 proven, 178 probable, and 106 possible IA cases to be identified. A higher favorable 12-week response rate was obtained with voriconazole (54.7%) than with AmB (29.9%) (P < .0001). Survival was higher for voriconazole for mycologically documented (probable/proven) IA (70.2%) than with AmB (54.9%) (P = .010). Higher response rates were obtained in possible IA treated with voriconazole vs AmB with the same magnitude of difference (26.2%; 95% confidence interval [CI], 7.2%-45.3%) as in mycologically documented episodes (24.3%; 95% CI, 11.9%-36.7%), suggesting that possible cases are true IA. CONCLUSIONS: Recategorization resulted in a better identification of the episodes and confirmed the higher efficacy of voriconazole over AmB deoxycholate in mycologically documented IA.
RCT Entities:
BACKGROUND: Strict definition of invasive aspergillosis (IA) cases is required to allow precise conclusions about the efficacy of antifungal therapy. The Global Comparative Aspergillus Study (GCAS) compared voriconazole to amphotericin B (AmB) deoxycholate for the primary therapy of IA. Because predefined definitions used for this trial were substantially different from the consensus definitions proposed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group in 2008, we recategorized the 379 episodes of the GCAS according to the later definitions. METHODS: The objectives were to assess the impact of the current definitions on the classification of the episodes and to provide comparative efficacy for probable/proven and possible IA in patients treated with either voriconazole or AmB. In addition to original data, we integrated the results of baseline galactomannan serum levels obtained from 249 (65.7%) frozen samples. The original response assessment was accepted unchanged. RESULTS: Recategorization allowed 59 proven, 178 probable, and 106 possible IA cases to be identified. A higher favorable 12-week response rate was obtained with voriconazole (54.7%) than with AmB (29.9%) (P < .0001). Survival was higher for voriconazole for mycologically documented (probable/proven) IA (70.2%) than with AmB (54.9%) (P = .010). Higher response rates were obtained in possible IA treated with voriconazole vs AmB with the same magnitude of difference (26.2%; 95% confidence interval [CI], 7.2%-45.3%) as in mycologically documented episodes (24.3%; 95% CI, 11.9%-36.7%), suggesting that possible cases are true IA. CONCLUSIONS: Recategorization resulted in a better identification of the episodes and confirmed the higher efficacy of voriconazole over AmB deoxycholate in mycologically documented IA.
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Authors: Samuel M Gonçalves; Daniela Antunes; Luis Leite; Toine Mercier; Rob Ter Horst; Joana Vieira; Eduardo Espada; Carlos Pinho Vaz; Rosa Branca; Fernando Campilho; Fátima Freitas; Dário Ligeiro; António Marques; Frank L van de Veerdonk; Leo A B Joosten; Katrien Lagrou; Johan Maertens; Mihai G Netea; João F Lacerda; António Campos; Cristina Cunha; Agostinho Carvalho Journal: mBio Date: 2021-05-28 Impact factor: 7.867