Skip to main content

Research Repository

Advanced Search

Biomarker Driven Antifungal Stewardship (BioDriveAFS) in acute leukaemia—a multi-centre randomised controlled trial to assess clinical and cost effectiveness: a study protocol for a randomised controlled trial

Flett, Lydia; Abdelatif, Radwa; Akhtar Baz, Sarah; Brady, Samantha; Corbacho, Belén; Common, Kate; Cowling, Abbie; Fairhurst, Caroline; Fitzmaurice, Ellie; Gandhi, Shreyans; Hilton, Andrea; Hope, William; Howard, Alex; Laycock, Joanne; Lillie, Patrick; Mitchell, Gemma; Parker, Adwoa; Peel, Mary; Sheard, Laura; Sneddon, Jacqueline; Taynton, Thomas; Tharmanathan, Puvan; Torgerson, David; Wang, Han‑I; Allsup, David; Barlow, Gavin

Authors

Lydia Flett

Radwa Abdelatif

Sarah Akhtar Baz

Samantha Brady

Belén Corbacho

Kate Common

Abbie Cowling

Caroline Fairhurst

Ellie Fitzmaurice

Shreyans Gandhi

Profile Image

Dr Andrea Hilton A.Hilton@hull.ac.uk
Reader and Programme director, Non-Medical Prescribing

William Hope

Alex Howard

Joanne Laycock

Patrick Lillie

Gemma Mitchell

Adwoa Parker

Mary Peel

Laura Sheard

Jacqueline Sneddon

Thomas Taynton

Puvan Tharmanathan

David Torgerson

Han‑I Wang

Profile Image

Dr David Allsup D.J.Allsup@hull.ac.uk
Senior Lecturer in Haematology and Honorary Consultant

Gavin Barlow



Abstract

Background Acute leukaemias (AL) are life-threatening blood cancers that can be potentially cured with treatment involving myelosuppressive, multiagent, intensive chemotherapy (IC). However, such treatment is associated with a risk of serious infection, in particular invasive fungal infection (IFI) associated with prolonged neutropenia. Current practice guidelines recommend primary antifungal (AF) prophylaxis to be administered to high-risk patients
to reduce IFI incidence. AFs are also used empirically to manage prolonged neutropenic fever. Current strategies lead to substantial overuse of AFs. Galactomannan (GM) and β-D-glucan (BG) biomarkers are also used to diagnose IFI. Combining both biomarkers may enhance the predictability of IFI compared to administering each test alone. Currently, no large-scale randomised controlled trial (RCT) has directly compared a biomarker-based diagnostic screening
strategy without AF prophylaxis to AF prophylaxis (without systematic biomarker testing).
Methods BioDriveAFS is a multicentre, parallel, two-arm RCT of 404 participants from UK NHS Haematology departments. Participants will be allocated on a 1:1 basis to receive either a biomarker-based antifungal stewardship (AFS) strategy, or a prophylactic AF strategy, which includes existing standard of care (SoC). The co-primary outcomes will be AF exposure in the 12-month post randomisation and the patient-reported EQ-5D-5L measured at 12-month post randomisation. Secondary outcomes will include total AF exposure, probable/proven IFI, survival (all-cause mortality and IFI mortality), IFI treatment outcome, AF-associated adverse effects/events/complications, resource use, episodes of neutropenic fever requiring hospital admission or outpatient management, AF resistance in fungi (non-invasive and invasive) and a Desirability of Outcome Ranking. The trial will have an internal pilot phase during the first 9 months. A mixed methods process evaluation will be integrated in parallel to the internal pilot phase and full trial, aiming to robustly assess how the intervention is delivered. Cost-effectiveness analysis will also be performed.
Discussion The BioDriveAFS trial aims to further the knowledge of strategies that will safely optimise AF use through comparison of the clinical and cost-effectiveness of a biomarker-led diagnostic strategy versus prophylactic AF to prevent and manage IFI within acute leukaemia. The evidence generated from the study will help inform global clinical practice and approaches within antifungal stewardship.

Citation

Flett, L., Abdelatif, R., Akhtar Baz, S., Brady, S., Corbacho, B., Common, K., …Barlow, G. (2024). Biomarker Driven Antifungal Stewardship (BioDriveAFS) in acute leukaemia—a multi-centre randomised controlled trial to assess clinical and cost effectiveness: a study protocol for a randomised controlled trial. Trials, 25, Article 427. https://doi.org/10.1186/s13063-024-08272-w

Journal Article Type Article
Acceptance Date Jun 19, 2024
Online Publication Date Jun 28, 2024
Publication Date Jun 28, 2024
Deposit Date Jul 1, 2024
Publicly Available Date Jul 2, 2024
Journal Trials
Print ISSN 1745-6215
Publisher Springer Verlag
Peer Reviewed Peer Reviewed
Volume 25
Article Number 427
DOI https://doi.org/10.1186/s13063-024-08272-w
Keywords Acute leukaemia; Galactomannan; Beta-D-Glucan; Antifungal stewardship; Invasive fungal infection; Apergillosis
Public URL https://hull-repository.worktribe.com/output/4730516

Files

Published article (4.5 Mb)
PDF

Publisher Licence URL
http://creativecommons.org/licenses/by/4.0

Copyright Statement
© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which
permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the
original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or
other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line
to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this
licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.




You might also like



Downloadable Citations