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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


Lydia Flett

Radwa Abdelatif

Sarah Akhtar Baz

Samantha Brady

Belén Corbacho

Kate Common

Abbie Cowling

Caroline Fairhurst

Ellie Fitzmaurice

Shreyans Gandhi

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Dr Andrea Hilton
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

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Dr David Allsup
Senior Lecturer in Haematology and Honorary Consultant

Gavin Barlow


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.


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.

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
Keywords Acute leukaemia; Galactomannan; Beta-D-Glucan; Antifungal stewardship; Invasive fungal infection; Apergillosis
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