PDF(Pubmed)
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.
CONCLUSIONS: 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.
BACKGROUND: ISRCTN11633399. Registered 24/06/2022.
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.
CONCLUSIONS: 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.
BACKGROUND: ISRCTN11633399. Registered 24/06/2022.
摘要：
背景：急性白血病（AL）是危及生命的血液癌症，可以通过涉及骨髓抑制的治疗治愈，多智能体，强化化疗（IC）。然而,这种治疗与严重感染的风险有关，特别是与长期中性粒细胞减少相关的侵袭性真菌感染（IMF）。当前的实践指南建议对高危患者进行初级抗真菌（AF）预防，以降低FI发生率。AFs也用于经验管理持续的中性粒细胞减少性发热。当前的策略导致AF的大量过度使用。半乳甘露聚糖(GM)和β-D-葡聚糖(BG)生物标记物也用于诊断IFI。与单独施用每个测试相比,两种生物标志物的组合可以增强FI的可预测性。目前,没有大规模随机对照试验(RCT)直接比较基于生物标志物的诊断筛查策略,而不进行AF预防与AF预防(不进行系统生物标志物检测).
方法：BioDriveAFS是一个多中心，平行,来自英国NHS血液科的404名参与者的双臂RCT。参与者将按1：1的比例分配，以接受基于生物标志物的抗真菌管理（AFS）策略。或预防性房颤策略，其中包括现有的护理标准(SoC)。共同的主要结果将是随机化后12个月的AF暴露和在随机化后12个月测量的患者报告的EQ-5D-5L。次要结果将包括总房颤暴露，可能的/已证实的Iv,生存率（全因死亡率和国际金融机构死亡率），FI治疗结果，房颤相关不良反应/事件/并发症,资源使用,需要入院或门诊治疗的中性粒细胞减少性发热发作，真菌中的AF抗性(非侵入性和侵入性)和结果排序的期望性。该试验将在前9个月进行内部试点阶段。混合方法过程评估将与内部试点阶段和全面试验并行整合，旨在有力地评估干预措施是如何实施的。还将进行成本效益分析。
结论：BioDriveAFS试验旨在通过比较生物标志物主导的诊断策略与预防性AF的临床和成本效益，进一步了解安全地优化AF使用的策略，以预防和管理急性白血病中的IFI。该研究产生的证据将有助于在抗真菌管理中告知全球临床实践和方法。
背景：ISRCTN11633399。注册24/06/2022。
方法：BioDriveAFS是一个多中心，平行,来自英国NHS血液科的404名参与者的双臂RCT。参与者将按1：1的比例分配，以接受基于生物标志物的抗真菌管理（AFS）策略。或预防性房颤策略，其中包括现有的护理标准(SoC)。共同的主要结果将是随机化后12个月的AF暴露和在随机化后12个月测量的患者报告的EQ-5D-5L。次要结果将包括总房颤暴露，可能的/已证实的Iv,生存率（全因死亡率和国际金融机构死亡率），FI治疗结果，房颤相关不良反应/事件/并发症,资源使用,需要入院或门诊治疗的中性粒细胞减少性发热发作，真菌中的AF抗性(非侵入性和侵入性)和结果排序的期望性。该试验将在前9个月进行内部试点阶段。混合方法过程评估将与内部试点阶段和全面试验并行整合，旨在有力地评估干预措施是如何实施的。还将进行成本效益分析。
结论：BioDriveAFS试验旨在通过比较生物标志物主导的诊断策略与预防性AF的临床和成本效益，进一步了解安全地优化AF使用的策略，以预防和管理急性白血病中的IFI。该研究产生的证据将有助于在抗真菌管理中告知全球临床实践和方法。
背景：ISRCTN11633399。注册24/06/2022。
