Superiority trials in invasive aspergillosis: a harsh reality check with the IA-DUET (HOVON502) trial

Hanne Lamberink; Sammy Huygens; Robina Aerts; Katrien Lagrou; Elena van Leeuwen-Segarceanu; Tom Lodewyck; Laurens Nieuwenhuizen; Maarten F Corsten; Ine Moors; Sophie Servais; Julien De Greef; Maya Hites; Astrid Demandt; Alexander Schauwvlieghe; Johan Maertens; Bart Rijnders

doi:10.1093/cid/ciae501

Superiority trials in invasive aspergillosis: a harsh reality check with the IA-DUET (HOVON502) trial

Clin Infect Dis. 2024 Oct 8:ciae501. doi: 10.1093/cid/ciae501. Online ahead of print.

Authors

Hanne Lamberink¹, Sammy Huygens^{1

2}, Robina Aerts^{3

4}, Katrien Lagrou^{4

5}, Elena van Leeuwen-Segarceanu⁶, Tom Lodewyck⁷, Laurens Nieuwenhuizen⁸, Maarten F Corsten⁹, Ine Moors², Sophie Servais¹⁰, Julien De Greef¹¹, Maya Hites¹², Astrid Demandt¹³, Alexander Schauwvlieghe⁷, Johan Maertens³, Bart Rijnders¹

Affiliations

¹ Department of Internal Medicine, Section of Infectious Diseases and department of Medical Microbiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
² Department of Hematology, Ghent University Hospital, Ghent, Belgium.
³ Department of Hematology, University Hospitals Leuven, Leuven, Belgium.
⁴ Department of Microbiology, Immunology and transplantation, KU Leuven, Leuven, Belgium.
⁵ Department of Laboratory Medicine and National Reference Center for Mycosis, Excellence Center for Medical Mycology (ECMM), University Hospitals Leuven, Leuven, Belgium.
⁶ Department of Internal Medicine, St. Antonius Hospital Nieuwegein, The Netherlands.
⁷ Department of Hematology, AZ St-Jan Brugge-Oostende Hospital, Bruges, Belgium.
⁸ Department of Hematology, Maxima Medical Center, Eindhoven/Veldhoven, The Netherlands.
⁹ Department of Hematology, Meander Medical Center, Amersfoort, The Netherlands.
¹⁰ Department of Hematology, University Hospital of Liège, Liège, Belgium.
¹¹ Department of Internal Medicine and Infectious Diseases, Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium.
¹² Clinic of Infectious Diseases, Hôpital Universitaire de Bruxelles, Brussels, Belgium.
¹³ Division of Hematology, Department of Internal Medicine, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.

PMID: 39378343
DOI: 10.1093/cid/ciae501

Abstract

The IA-DUET study aimed to compare azole-echinocandin combination with azole monotherapy for invasive aspergillosis. Recruitment was hindered by patient ineligibility, competing studies, and guidelines favoring combination therapy when azole resistance was unknown. The low IA-attributable mortality suggests future trials may benefit from cluster randomization or composite endpoints to enhance efficiency.

Keywords: azole; combination therapy; echinocandin; invasive aspergillosis.