Recombinant factor VIIa versus placebo for spontaneous intracerebral haemorrhage within 2 h of symptom onset (FASTEST): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial BACKGROUND: Recombinant factor VIIa has been shown to slow bleeding in patients with intracerebral haemorrhage (ICH), but no haemostatic agent has been shown to improve clinical outcomes. We aimed to evaluate the safety, clinical efficacy, and effect on growth of ICH and intraventricular haemorrhage (IVH) of recombinant factor VIIa in patients with acute spontaneous ICH who were most likely to benefit from treatment with this agent. METHODS: We conducted a multicentre, prospective, double-blind, randomised, placebo-controlled, adaptive, phase 3 trial (FASTEST) at 93 sites across the USA, Japan, Canada, Spain, Germany, and the UK. Adults aged 18-80 years with a spontaneous ICH of 2-60 mL, IVH in less than two-thirds of one lateral ventricle or in less than a third of both lateral ventricles, a Glasgow Coma Scale score of at least 8, no evidence of recent ischaemic stroke or myocardial infarction, no recent use of anticoagulation medication or other structural cause of ICH, and who had been treated with study medication within 2 h of stroke onset or last known well were eligible for inclusion. Patients were randomly assigned (1:1) by a simple randomisation scheme to either 80 μg/kg recombinant factor VIIa (intervention group) or an identical placebo (placebo group), administered intravenously over 2 min. All investigators and participants were masked to allocated group assignment. The primary outcome was functional outcome at 180 days, measured by modified Rankin Scale (mRS; score 0-2, 3, and 4-6) and analysed by intention to treat in all randomly assigned patients. The primary safety outcome was life-threatening thromboembolic events during the first 4 days, assessed in all randomly assigned participants. The secondary aim was change in ICH volume and ICH plus IVH volume between baseline and 24 h of treatment administration. We performed an ordinal logistic regression, adjusted for age, baseline ICH volume, baseline IVH volume, and pre-stroke mRS. Preplanned interim analyses, including adaptive sample size re-estimation and enrichment to a younger subgroup (aged ≤70 years), were also conducted. This trial is registered with ClinicalTrials.gov (NCT03496883) and is closed to new participants. FINDINGS: Between Dec 3, 2021, and Oct 1, 2025, we screened 3288 patients, of whom 626 participants were randomly assigned and included in the intention-to-treat analyses: 298 (48%) in the placebo group and 328 (52%) in the intervention group. 216 (35%) participants were female and 410 (65%) were male, with a mean age of 61 years (SD 12). Mean time from stroke onset to administration of study drug was 100 min (SD 22). The trial met the prespecified stopping criteria for futility at the second interim analysis. There was no differential effect in the primary clinical outcome measure of mRS at 180 days between the intervention group and placebo group (adjusted common odds ratio 1·09 [95% CI 0·79-1·51]; p=0·61). Life-threatening thromboembolic complications within 4 days occurred in 15 (<5%) participants in the intervention group and in four (1%) in the placebo group (relative risk 3·41 [95% CI 1·14-10·15]; p=0·020). Compared with placebo, recombinant factor VIIa was associated with decreased growth of ICH (-3·7 mL [95% CI -5·4 to -1·9]) and of ICH plus IVH growth (-5·2 mL [-7·6 to -2·8]) between baseline and CT scan at 24 h. INTERPRETATION: Recombinant factor VIIa administered within 2 h of ICH onset slowed haematoma growth, but did not improve functional outcomes and showed a small increased risk of life-threatening thromboembolic complications. Further testing of recombinant factor VIIa in patients with the greatest risk of continued bleeding is ongoing. FUNDING: National Institute of Neurological Diseases and Stroke, Japan Agency for Medical Research and Development, and Novo Nordisk.

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Recombinant factor VIIa versus placebo for spontaneous intracerebral haemorrhage within 2 h of symptom onset (FASTEST) (...)
by Broderick et al.
www.transfusionevidencelibrary.com/alerts/artic...
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Interventions to Prevent Intraventricular Haemorrhage in Preterm Neonates: An Umbrella Review of Systematic Reviews and Meta-Analyses INTRODUCTION: Intraventricular haemorrhage (IVH) leads to significant morbidity among preterm infants. We conducted an overview of systematic reviews of RCTs assessing the effects of perinatal/neonatal interventions in reducing IVH among preterm infants. METHODS: PubMed, Embase, Cochrane database for systematic reviews, and systematic review repositories were searched for meta-analyses of RCTs involving preterm infants or women at high risk of preterm birth and reporting on IVH. Metaumbrella package of R software was used to pool outcome data for each intervention. Quality of the systematic reviews was assessed using AMSTAR 2 tool. Certainty of evidence (COE) was reported using GRADE recommendations. RESULTS: A total of 148 systematic reviews (110 Cochrane vs. 38 non-Cochrane) were included. Postnatal interventions were reported in 118 reviews. Severe IVH was reported in 100/148 reviews that included 39,483 infants and 20,400 antenatal women. In total, 78% (n = 116) of the reviews were rated high or moderate quality on AMSTAR-2 assessment. Antenatal corticosteroids and magnesium sulphate for imminent preterm birth, volume-targeted ventilation, early rescue surfactant administration through thin catheter, prophylactic indomethacin significantly reduced the rates of severe IVH (moderate COE). Use of respiratory function monitors and heated humidified respiratory gases in the delivery room and early prophylactic erythropoietin supplementation for preterm infants may reduce the rates of severe IVH (very low COE). DISCUSSION: Antenatal steroids and magnesium sulphate administration and early neonatal lung protective strategies reduce the rates of IVH in preterm neonates. Adequately powered RCTs evaluating IVH care bundles with long-term follow-up are required.

🔗 #TransfusionEvidence Library link to:
Interventions to Prevent Intraventricular Haemorrhage in Preterm Neonates: An Umbrella Review of Systematic Reviews and Meta-Analyses
by Bhanushali et al.
www.transfusionevidencelibrary.com/alerts/artic...
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N-acetylcysteine reduces incidence and duration of linezolid-associated thrombocytopenia in critically ill patients: A randomized controlled trial Linezolid-associated thrombocytopenia (LAT) limits its use in critically ill patients. This double-blind, randomized, placebo-controlled trial evaluated intravenous N-acetylcysteine (IV NAC) for LAT prevention in 250 critically ill adults receiving linezolid for ≥ 48 h. Patients received IV NAC (600 mg every 12 h) or placebo. The primary endpoint was LAT incidence (platelet count <150 × 10 ³/mm³ or >50 % reduction from baseline). NAC significantly reduced LAT incidence (16.8 % vs. 41.6 %; p < 0.001), platelet transfusions (1.6 % vs. 11.2 %; p = 0.003), and linezolid discontinuations (6.4 % vs. 32.0 %; p < 0.001). NAC delayed LAT onset (adjusted hazard ratio 0.24; p < 0.001) and accelerated platelet recovery (adjusted hazard ratio 3.88; p = 0.011), with greatest benefit in moderate-severity cases. These findings suggest IV NAC may offer a preventive benefit against LAT in critically ill patients, though multicenter validation is needed to confirm generalizability across diverse clinical settings. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT05944458. Registered on July 6, 2023.

🔗 #TransfusionEvidence Library link to:
N-acetylcysteine reduces incidence and duration of linezolid-associated thrombocytopenia in critically ill patients: A randomized controlled trial
by Abdeltawab et al.
www.transfusionevidencelibrary.com/alerts/artic...
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Preventive interventions for vasovagal reactions in whole blood donors: a cluster-randomised, stepped-wedge, crossover trial of 73 sites involving 1·4 million donors in England BACKGROUND: Vasovagal reactions are the most common acute systemic complications of whole blood donations and are associated with significant morbidity and medicolegal costs. Blood services worldwide have implemented various strategies to prevent vasovagal reactions, often without robust evidence. We compared standard practice in England with four vasovagal reaction prevention interventions used in other services or previously tested in small-scale studies. METHODS: This cluster-randomised, stepped-wedge, crossover trial involved 73 blood donation sites (clusters) across England, UK. Each site was randomly allocated to one of 64 possible sequences for implementing one or more of four interventions over four 9-month periods, yielding a total of 292 site-periods for a 36-month overall trial duration. Participants within each period were not unique, as repeat donations were included. Cluster randomisation was chosen for operational feasibility. Potential carry-over effects were minimised by use of stepped-wedge, crossover, and factorial design elements. The interventions assessed were: 500 mL pre-donation isotonic drink (vs standard 500 mL plain water), extended 3-minute post-donation rest on the donation chair (vs standard 2-minute rest), modified applied muscle tension (AMT) exercise (vs current AMT practice); and psychosocial intervention using preparatory materials (vs no materials). The primary outcome was in-session vasovagal reaction with loss of consciousness. Analysis was by intention-to-treat, including data from all donors attending the donation sites during the trial, unless the donor opted-out. This trial registered with isrctn.com (ISRCTN 10412338) and is complete. FINDINGS: Between Nov 4, 2019, and Nov 3, 2022, we recruited 1 379 095 blood donors who made 4 134 712 blood donations. The median age of donors at time of baseline trial visit was 41 years (IQR 30-54), 785 271 (56·9%) of 1 379 095 donors were female and 593 824 (43·1%) were male. 461 954 (33·5%) were first-time donors. We recorded 4388 vasovagal reactions with loss of consciousness and 60 517 total in-session vasovagal reactions (ie, with and without loss of consciousness). Compared with standard practices, none of the interventions clearly reduced the primary outcome (joint p=0·21) with an odds ratio of 0·98 (95% CI 0·92-1·04) for isotonic drink, 0·99 (0·92-1·06) for extended chair rest, 1·12 (1·00-1·26) for modified AMT, and 1·03 (0·93-1·14) for psychosocial intervention. Absolute event rates per 10 000 donations were 10·7 without intervention and 10·5 with intervention. Findings were similar for total in-session vasovagal reactions with higher absolute event rates. INTERPRETATION: Four interventions used to prevent donation-related vasovagal reactions showed no clear benefits compared with standard practices in England, suggesting potential policy implications for blood services worldwide to streamline donation practices and save resources. FUNDING: NHS Blood and Transplant and the NIHR Blood and Transplant Research Unit in Donor Health and Behaviour (formerly Donor Health and Genomics).

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Preventive interventions for vasovagal reactions in whole blood donors: a cluster-randomised, stepped-wedge, crossover trial of 73 sites involving 1·4 million donors in England
by Kaptoge et al.
www.transfusionevidencelibrary.com/alerts/artic...
#MedSky

Episode 3: World Anaemia Day Talking Transfusion: The Transfusion Evidence Round-Up Podcast · Episode

Brought to you by ISBT & the transfusionlib.bsky.social this quarterly round-up curates high-quality evidence to keep you at the forefront of transfusion medicine.

🎧Listen now: open.spotify.com/episode/2B7P...

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