Pre-emptive

Introduction: Voriconazole is a first-line therapy for invasive aspergillosis, but its use is complicated by pronounced pharmacokinetic variability, largely driven by Methods: We conducted a pragmatic, randomized, single-blind trial (EudraCT: 2019-000376-41; ClinicalTrials.gov: NCT04238884). Pediatric hematology patients at high risk of aspergillosis were randomized (1:1) to receive either standard weight-based dosing (Control) or preemptive Results: Thirty-two patients (16 per arm) were evaluated. The experimental arm had a higher proportion of patients achieving the therapeutic range compared to the control arm, but not statistically significant (37.5% vs. 12.5%, p = 0.200). The proportion of patients with subtherapeutic exposure (<1.0 mg/L) was lower in the genotype-guided arm than in the standard-of-care arm (31.3% vs. 68.8%, p = 0.034). Supratherapeutic levels were comparable between groups (25% vs. 18.8%, p > 0.900). An exploratory cost-consequence analysis was associated with a mean difference in direct medical costs of €5,819 per patient in favour of the genotype-guided arm, although this difference was not statistically significant (p = 0.300). Conclusion: Preemptive Clinical Trial Registration: https://clinicaltrials.gov/study/NCT04238884; https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-000376-41/ES, identifier EudraCT: 2019-000376-41; NCT04238884.