CRE RESPOND continues to lead innovation in precision infectious diseases therapy through the PRAGMATIC trial (PhaRmAcoGenoMics for better treatment of fungAl infecTIons)—a landmark academic achievement for the Centre. Funded by the Australian Government’s Medical Research Future Fund (MRFF), PRAGMATIC is the first pharmacogenomic clinical trial focused on improving treatment of invasive fungal infections through genotype‑informed antifungal dosing.
Invasive fungal infections are a serious complication of cancer treatment and carry high morbidity and mortality, particularly among patients with haematological malignancy. Voriconazole is a widely used first‑line antifungal treatment, but its clinical use is challenging due to a narrow therapeutic range and large inter‑patient variability in drug exposure. Much of this variability is driven by genetic differences in the CYP2C19 enzyme, which affects how patients metabolise voriconazole. Despite this, genotype‑guided dosing is not part of routine care.
The PRAGMATIC trial addresses this gap by evaluating a pragmatic, patient‑centred precision dosing strategy that combines pharmacogenomic testing, therapeutic drug monitoring (TDM), and Bayesian dosing software. The study is a parallel‑group, randomised (1:1) trial aiming to recruit at least 104 patients aged two years and older, with and without haematological malignancy, who are receiving voriconazole for the prophylaxis or treatment of invasive fungal infection.
Participants are allocated to either standard care or precision care, with the latter using genotype and TDM results to guide structured dose adjustments. The primary endpoint is achievement of a therapeutic voriconazole trough concentration by Day 8.
Importantly, recruitment is well under way at 7 sites including the Royal Brisbane & Women’s Hospital, the Queensland Children’s Hospital; the Westmead Hospital and Sydney Childrens Hospital Network; the Peter MacCallum Cancer Centre, the Royal Adelaide Hospital and one US site at the Fred Hutchinson Cancer Centre. This collaboration reflects strong clinical engagement and highlights the trial’s relevance to real‑world practice. By integrating genomics into everyday prescribing, PRAGMATIC exemplifies CRE RESPOND’s commitment to translating precision medicine into meaningful patient benefit.
