Dataset Information

The SWiFT trial (Study of Whole Blood in Frontline Trauma)-the clinical and cost effectiveness of pre-hospital whole blood versus standard care in patients with life-threatening traumatic haemorrhage: study protocol for a multi-centre randomised controlled trial.

ABSTRACT:

Background

Early blood transfusion improves survival in patients with life-threatening bleeding, but the optimal transfusion strategy in the pre-hospital setting has yet to be established. Although there is some evidence of benefit with the use of whole blood, there have been no randomised controlled trials exploring the clinical and cost effectiveness of pre-hospital administration of whole blood versus component therapy for trauma patients with life-threatening bleeding. The aim of this trial is to determine whether pre-hospital leukocyte-depleted whole blood transfusion is better than standard care (blood component transfusion) in reducing the proportion of participants who experience death or massive transfusion at 24 h.

Methods

This is a multi-centre, superiority, open-label, randomised controlled trial with internal pilot and within-trial cost-effectiveness analysis. Patients of any age will be eligible if they have suffered major traumatic haemorrhage and are attended by a participating air ambulance service. The primary outcome is the proportion of participants with traumatic haemorrhage who have died (all-cause mortality) or received massive transfusion in the first 24 h from randomisation. A number of secondary clinical, process, and safety endpoints will be collected and analysed. Cost (provision of whole blood, hospital, health, and wider care resource use) and outcome data will be synthesised to present incremental cost-effectiveness ratios for the trial primary outcome and cost per quality-adjusted life year at 90 days after injury. We plan to recruit 848 participants (a two-sided test with 85% power, 5% type I error, 1-1 allocation, and one interim analysis would require 602 participants-after allowing for 25% of participants in traumatic cardiac arrest and an additional 5% drop out, the sample size is 848).

Discussion

The SWiFT trial will recruit 848 participants across at least ten air ambulances services in the UK. It will investigate the clinical and cost-effectiveness of whole blood transfusion versus component therapy in the management of patients with life-threatening bleeding in the pre-hospital setting.

Trial registration

ISRCTN: 23657907; EudraCT: 2021-006876-18; IRAS Number: 300414; REC: 22/SC/0072, 21 Dec 2021.

SUBMITTER: Smith JE

PROVIDER: S-EPMC10644622 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Publications

The SWiFT trial (Study of Whole Blood in Frontline Trauma)-the clinical and cost effectiveness of pre-hospital whole blood versus standard care in patients with life-threatening traumatic haemorrhage: study protocol for a multi-centre randomised controlled trial.

Smith Jason E JE Barnard Ed B G EBG Brown-O'Sullivan Charlie C Cardigan Rebecca R Davies Jane J Hawton Annie A Laing Emma E Lucas Joanne J Lyon Richard R Perkins Gavin D GD Smith Laura L Stanworth Simon J SJ Weaver Anne A Woolley Tom T Green Laura L

Trials 20231114 1

<h4>Background</h4>Early blood transfusion improves survival in patients with life-threatening bleeding, but the optimal transfusion strategy in the pre-hospital setting has yet to be established. Although there is some evidence of benefit with the use of whole blood, there have been no randomised controlled trials exploring the clinical and cost effectiveness of pre-hospital administration of whole blood versus component therapy for trauma patients with life-threatening bleeding. The aim of thi ...[more]

PMID: 37964393

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Project description:BackgroundThere is increasing interest in the timely administration of concentrated sources of fibrinogen to patients with major traumatic bleeding. Following evaluation of early cryoprecipitate in the CRYOSTAT 1 trial, we explored the use of fibrinogen concentrate, which may have advantages of more rapid administration in acute haemorrhage. The aims of this pragmatic study were to assess the feasibility of fibrinogen concentrate administration within 45 minutes of hospital admission and to quantify efficacy in maintaining fibrinogen levels ≥ 2 g/L during active haemorrhage.MethodsWe conducted a blinded, randomised, placebo-controlled trial at five UK major trauma centres with adult trauma patients with active bleeding who required activation of the major haemorrhage protocol. Participants were randomised to standard major haemorrhage therapy plus 6 g of fibrinogen concentrate or placebo.ResultsTwenty-seven of 39 participants (69%; 95% CI, 52-83%) across both arms received the study intervention within 45 minutes of admission. There was some evidence of a difference in the proportion of participants with fibrinogen levels ≥ 2 g/L between arms (p = 0.10). Fibrinogen levels in the fibrinogen concentrate (FgC) arm rose by a mean of 0.9 g/L (SD, 0.5) compared with a reduction of 0.2 g/L (SD, 0.5) in the placebo arm and were significantly higher in the FgC arm (p < 0.0001) at 2 hours. Fibrinogen levels were not different at day 7. Transfusion use and thromboembolic events were similar between arms. All-cause mortality at 28 days was 35.5% (95% CI, 23.8-50.8%) overall, with no difference between arms.ConclusionsIn this trial, early delivery of fibrinogen concentrate within 45 minutes of admission was not feasible. Although evidence points to a key role for fibrinogen in the treatment of major bleeding, researchers need to recognise the challenges of timely delivery in the emergency setting. Future studies must explore barriers to rapid fibrinogen therapy, focusing on methods to reduce time to randomisation, using 'off-the-shelf' fibrinogen therapies (such as extended shelf-life cryoprecipitate held in the emergency department or fibrinogen concentrates with very rapid reconstitution times) and limiting the need for coagulation test-based transfusion triggers.Trial registrationISRCTN67540073 . Registered on 5 August 2015.

Project description:BackgroundHaemorrhage remains a leading cause of morbidity and mortality in trauma patients. Fibrinogen is an essential endogenous component of haemostasis and the plasma level is associated with bleeding, transfusion and outcome. Fibrinogen concentrate is widely used to correct acquired hypofibrinogenaemia, recommended by several international guidelines for the treatment of trauma patients, but evidence is lacking regarding the treatment safety and efficacy. We aim to assess the efficacy and safety of an immediate pre-emptive first-line treatment with fibrinogen concentrate in patients with trauma haemorrhage in need of haemostatic resuscitation.Methods/designThis is a single-centre, randomized (1:1, active:placebo), placebo-controlled, double-blinded, investigator-initiated phase II trial. The trial population consists of 40 adult patients (>18 years) with traumatic, critical bleeding admitted to the Level 1 Trauma Centre at Rigshospitalet in Copenhagen, with immediate need for blood transfusion on arrival and an expected need for haemostatic resuscitation with multiple transfusions during the initial resuscitation. Patients will receive either pre-emptive administration of a bolus dose of 60-70 mg/kg fibrinogen concentrate (Riastap®) or placebo 0.9 % saline in equal volume to active treatment, both given as intravenous infusion blinded for the person administering the infusion. The primary end point is the change in thrombelastograph (TEG®) functional fibrinogen maximum amplitude in millimetres at 15 min after the intervention. The follow-up period on safety events and mortality will be until day 30. To detect a difference in the change from baseline to the 15-minute post-randomization measurement of 6-8 mm in TEG® functional fibrinogen maximum amplitude with a power of 0.90 and alpha of 0.05, we require 19 patients in each group. We have chosen to include 40 patients, 20 evaluable patients in each randomization group in case of attrition, in the present trial.DiscussionPatients considered to be included in the trial will temporarily have a compromised consciousness because of the acute, critical bleeding related to trauma, so scientific guardians will co-sign the informed consent form. Next of kin and the patients' general practitioner or the patients will co-sign as soon as possible. This trial will test whether immediate pre-emptive fibrinogen concentrate administered to adult trauma patients as first-line treatment of trauma haemorrhage will increase the clot strength as evaluated by thrombelastography, transfusion requirements and survival in patients receiving haemostatic resuscitation according to current standard of care.Trial registrationEudraCT no. 2014-003978-16 (22/1 2015); ClinicalTrials.gov: NCT02344069 . Registered on 14 January 2015. Trial protocol version 4.2 (23-12-2014).

Project description:There is a lack of evidence evaluating cryoprecipitate transfusion in severe postpartum haemorrhage. We performed a pilot cluster-randomised controlled trial to evaluate the feasibility of a trial on early cryoprecipitate delivery in severe postpartum haemorrhage. Pregnant women (>24 weeks gestation), actively bleeding within 24 h of delivery and who required at least one unit of red blood cells were eligible. Women declining transfusion in advance or with inherited clotting deficiencies were not eligible. Four UK hospitals were randomly allocated to deliver either the intervention (administration of two pools of cryoprecipitate within 90 min of first red blood cell unit requested plus standard care), or the control group treatment (standard care, where cryoprecipitate is administered later or not at all). The primary outcome was the proportion of women who received early cryoprecipitate (intervention) vs. standard care (control). Secondary outcomes included consent rates, acceptability of the intervention, safety outcomes and preliminary clinical outcome data to inform a definitive trial. Between March 2019 and January 2020, 199 participants were recruited; 19 refused consent, leaving 180 for analysis (110 in the intervention and 70 in the control group). Adherence to assigned treatment was 32% (95%CI 23-41%) in the intervention group vs. 81% (95%CI 70-90%) in the control group. The proportion of women receiving cryoprecipitate at any time-point was higher in the intervention (60%) vs. control (31%) groups; the former had fewer red blood cell transfusions at 24 h (mean difference -0.6 units, 95%CI -1.2 to 0); overall surgical procedures (odds ratio 0.6, 95%CI 0.3-1.1); and intensive care admissions (odds ratio 0.4, 95%CI 0.1-1.1). There was no increase in serious adverse or thrombotic events in the intervention group. Staff interviews showed that lack of awareness and uncertainty about study responsibilities contributed to lower adherence in the intervention group. We conclude that a full-scale trial may be feasible, provided that protocol revisions are put in place to establish clear lines of communication for ordering early cryoprecipitate in order to improve adherence. Preliminary clinical outcomes associated with cryoprecipitate administration are encouraging and merit further investigation.

Project description:IntroductionAcute traumatic coagulopathy (ATC) in bleeding trauma patients increase in-hospital mortality. Fibrinogen concentrate (FC) and prothrombin complex concentrate (PCC) are two purified concentrates of clotting factors that have been used to treat ATC. However, there is a knowledge gap on their use compared with the standard of care, the transfusion of plasma.Methods and analysisThe factors in the initial resuscitation of severe trauma 2 trial is a multicentre, randomised, parallel-control, single-blinded, phase IV superiority trial. The study aims to address efficacy and safety of the early use of FC and PCC compared with a plasma-based resuscitation. Adult trauma patients requiring massive haemorrhage protocol activation on hospital arrival will receive FC 4 g and PCC 2000 IU or plasma 4 U, based on random allocation. The primary outcome is a composite of the cumulative number of all units of red cells, plasma and platelets transfused within 24 hours following admission. Secondary outcomes include measures of efficacy and safety of the intervention. Enrolment of 350 patients will provide an initial power >80% to demonstrate superiority for the primary outcome. After enrolment of 120 patients, a preplanned adaptive interim analysis will be conducted to reassess assumptions, check for early superiority demonstration or reassess the sample size for remainder of the study.Ethics and disseminationThe study has been approved by local and provincial research ethics boards and will be conducted according to the Declaration of Helsinki, Good Clinical Practice guidelines and regulatory requirements. As per the Tri-Council Policy Statement, patient consent will be deferred due to the emergency nature of the interventions. If superiority is established, results will have a major impact on clinical practice by reducing exposure to non-virally inactivated blood products, shortening the time for administration of clotting factors, correct coagulopathy more efficaciously and reduce the reliance on AB plasma.Trial registration numberNCT04534751, pre results.

Dataset Information

The SWiFT trial (Study of Whole Blood in Frontline Trauma)-the clinical and cost effectiveness of pre-hospital whole blood versus standard care in patients with life-threatening traumatic haemorrhage: study protocol for a multi-centre randomised controlled trial.

Background

Methods

Discussion

Trial registration

Publications

The SWiFT trial (Study of Whole Blood in Frontline Trauma)-the clinical and cost effectiveness of pre-hospital whole blood versus standard care in patients with life-threatening traumatic haemorrhage: study protocol for a multi-centre randomised controlled trial.

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