Therapeutic drug monitoring-guided treatment versus standard dosing of voriconazole for invasive aspergillosis in haematological patients: a multicentre, prospective, cluster randomised, crossover clinical trial

Veringa, A.; Bruggemann, R.J.; Span, L.F.R.; Biemond, B.J.; Boer, M.G.J. de; Heuvel, E.R. van den; ... ; Voriconazole ZonMw Study Grp (2023)

Article in monograph or in proceedings

Objectives: Voriconazole therapeutic drug monitoring (TDM) is recommended based on retrospective data and limited prospective studies. This study aimed to investigate whether TDM-guided voriconazole treat-ment is superior to standard treatment for invasive aspergillosis.Methods: A multicentre ( n = 10), prospective, cluster randomised, crossover clinical trial was performed in haematological patients aged >= 18 years treated with voriconazole. All patients received standard voriconazole dose at the start of treatment. Blood/serum/plasma was periodically collected after treat-ment initiation of voriconazole and repeated during treatment in both groups. The TDM group had mea-sured voriconazole concentrations reported back, with dose adjustments made as appropriate, while the non-TDM group had voriconazole concentrations measured only after study completion. The composite primary endpoint included response to treatment and voriconazole treatment discontinuation due to an adverse drug reaction related to voriconazole within 28 days after treatment initiation. Results: In total, 189 patients were enrolled in the study. For the composite primary endpoint, 74 patients were included in the non-TDM group and 68 patients in the TDM group. Here, no significant difference was found between both groups ( P = 0.678). However, more trough concentrations were found within the generally accepted range of 1-6 mg/L for the TDM group (74.0%) compared with the non-TDM group (64.0%) ( P < 0.001). Conclusions: In this trial, TDM-guided dosing of voriconazole did not show improved treatment outcome compared with standard dosing. We believe that these findings should open up the discussion for an approach to voriconazole TDM that includes drug exposure, pathogen susceptibility and host defence. Clinical trial registration: ClinicalTrials.gov registration no. NCT00893555.(c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

• Voriconazole
• Therapeutic drug monitoring
• Haematological malignancy
• Invasive fungal infection

• All authors: Veringa, A.; Bruggemann, R.J.; Span, L.F.R.; Biemond, B.J.; Boer, M.G.J. de; Heuvel, E.R. van den; Klein, S.K.; Kraemer, D.; Minnema, M.C.; Prakken, N.H.J.; Rijnders, B.J.A.; Swen, J.J.; Verweij, P.E.; Wondergem, M.J.; Ypma, P.F.; Blijlevens, N.; Kosterink, J.G.W.; Werf, T.S. van der; Alffenaar, J.W.C.; Voriconazole ZonMw Study Grp
• Date: 2023-01-28
• Title of host publication: International Journal of Antimicrobial Agents
• Volume: 61
• Issue: 2
• DOI: doi:10.1016/j.ijantimicag.2023.106711
• Link: https://www.sciencedirect.com/science/article/pii/S0924857923000031?via%...