Dataset Information

Viscoelastic haemostatic assay augmented protocols for major trauma haemorrhage (ITACTIC): a randomized, controlled trial.

ABSTRACT:

Purpose

Contemporary trauma resuscitation prioritizes control of bleeding and uses major haemorrhage protocols (MHPs) to prevent and treat coagulopathy. We aimed to determine whether augmenting MHPs with Viscoelastic Haemostatic Assays (VHA) would improve outcomes compared to Conventional Coagulation Tests (CCTs).

Methods

This was a multi-centre, randomized controlled trial comparing outcomes in trauma patients who received empiric MHPs, augmented by either VHA or CCT-guided interventions. Primary outcome was the proportion of subjects who, at 24 h after injury, were alive and free of massive transfusion (10 or more red cell transfusions). Secondary outcomes included 28-day mortality. Pre-specified subgroups included patients with severe traumatic brain injury (TBI).

Results

Of 396 patients in the intention to treat analysis, 201 were allocated to VHA and 195 to CCT-guided therapy. At 24 h, there was no difference in the proportion of patients who were alive and free of massive transfusion (VHA: 67%, CCT: 64%, OR 1.15, 95% CI 0.76-1.73). 28-day mortality was not different overall (VHA: 25%, CCT: 28%, OR 0.84, 95% CI 0.54-1.31), nor were there differences in other secondary outcomes or serious adverse events. In pre-specified subgroups, there were no differences in primary outcomes. In the pre-specified subgroup of 74 patients with TBI, 64% were alive and free of massive transfusion at 24 h compared to 46% in the CCT arm (OR 2.12, 95% CI 0.84-5.34).

Conclusion

There was no difference in overall outcomes between VHA- and CCT-augmented-major haemorrhage protocols.

SUBMITTER: Baksaas-Aasen K

PROVIDER: S-EPMC7550843 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundOutcome after spontaneous (non-traumatic) intracerebral haemorrhage (ICH) is influenced by haematoma volume; up to one-third of ICHs enlarge within 24 hours of onset. Early haemostatic therapy might improve outcome by limiting haematoma growth. This is an update of a Cochrane Review first published in 2006, and last updated in 2009.ObjectivesTo examine 1) the effectiveness and safety of individual classes of haemostatic therapies, compared against placebo or open control, in adults with acute spontaneous intracerebral haemorrhage, and 2) the effects of each class of haemostatic therapy according to the type of antithrombotic drug taken immediately before ICH onset (i.e. anticoagulant, antiplatelet, or none).Search methodsWe searched the Cochrane Stroke Trials Register, CENTRAL; 2017, Issue 11, MEDLINE Ovid, and Embase Ovid on 27 November 2017. In an effort to identify further published, ongoing, and unpublished randomised controlled trials (RCT), we scanned bibliographies of relevant articles and searched international registers of RCTs in November 2017.Selection criteriaWe sought randomised controlled trials (RCTs) of any haemostatic intervention (i.e. pro-coagulant treatments such as coagulation factors, antifibrinolytic drugs, or platelet transfusion) for acute spontaneous ICH, compared with placebo, open control, or an active comparator, reporting relevant clinical outcome measures.Data collection and analysisTwo authors independently extracted data, assessed risk of bias, and contacted corresponding authors of eligible RCTs for specific data if they were not provided in the published report of an RCT.Main resultsWe included 12 RCTs involving 1732 participants. There were seven RCTs of blood clotting factors versus placebo or open control involving 1480 participants, three RCTs of antifibrinolytic drugs versus placebo or open control involving 57 participants, one RCT of platelet transfusion versus open control involving 190 participants, and one RCT of blood clotting factors versus fresh frozen plasma involving five participants. We were unable to include two eligible RCTs because they presented aggregate data for adults with ICH and other types of intracranial haemorrhage. We identified 10 ongoing RCTs. Across all seven criteria in the 12 included RCTs, the risk of bias was unclear in 37 (44%), high in 16 (19%), and low in 31 (37%). Only one RCT was at low risk of bias in all criteria.In one RCT of platelet transfusion versus open control for acute spontaneous ICH associated with antiplatelet drug use, there was a significant increase in death or dependence (modified Rankin Scale score 4 to 6) at day 90 (70/97 versus 52/93; risk ratio (RR) 1.29, 95% confidence interval (CI) 1.04 to 1.61, one trial, 190 participants, moderate-quality evidence). All findings were non-significant for blood clotting factors versus placebo or open control for acute spontaneous ICH with or without surgery (moderate-quality evidence), for antifibrinolytic drugs versus placebo (moderate-quality evidence) or open control for acute spontaneous ICH (moderate-quality evidence), and for clotting factors versus fresh frozen plasma for acute spontaneous ICH associated with anticoagulant drug use (no evidence).Authors' conclusionsBased on moderate-quality evidence from one trial, platelet transfusion seems hazardous in comparison to standard care for adults with antiplatelet-associated ICH.We were unable to draw firm conclusions about the efficacy and safety of blood clotting factors for acute spontaneous ICH with or without surgery, antifibrinolytic drugs for acute spontaneous ICH, and clotting factors versus fresh frozen plasma for acute spontaneous ICH associated with anticoagulant drug use.Further RCTs are warranted, and we await the results of the 10 ongoing RCTs with interest.

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Project description:ObjectiveViscoelastic hemostatic assay (VHA) provides a graphical representation of a clot's lifespan and reflects the real time of coagulation. It has been used to guide trauma resuscitation; however, evidence of the effectiveness of VHAs is still limited. This systematic review aims to summarize the published evidence to evaluate the VHA-guided strategy in resuscitating trauma patients.MethodsThe PubMed, Embase, and Web of Science databases were searched from their inception to December 13, 2021. Randomized controlled trials (RCTs) or observational studies comparing VHA-guided transfusion to controls in resuscitating trauma patients were included in this systematic review.ResultsOf the 7743 records screened, ten studies, including two RCTs and eight observational studies, met the inclusion criteria. There was great heterogeneity concerning study design, enrollment criterion, VHA device, VHA-guided strategy, and control strategy. Thrombelastography (TEG) was used as a guiding tool for transfusion in eight studies, and rotational thromboelastometry (ROTEM), and TEG or ROTEM were used in the other two studies. The overall risk of bias assessment was severe or mild in RCTs and was severe or moderate in observational studies. The main outcomes reported from the included studies were blood transfusion (n = 10), mortality (n = 10), hospital length of stay (LOS) (n = 7), intensive care unit LOS (n = 7), and cost (n = 4). The effect of the VHA-guided strategy was not always superior to the control. Most of the studies did not find significant differences in the transfusion amount of red blood cells (n = 7), plasma (n = 5), platelet (n = 7), cryoprecipitate/fibrinogen (n = 7), and mortality (n = 8) between the VHA-guided group and control group. Notable, two RCTs showed that the VHA-guided strategy was superior or equal to the conventional coagulation test-guided strategy in reducing mortality, respectively.ConclusionAlthough some studies demonstrated VHA-guided strategy probable benefit in reducing the need for blood transfusion and mortality when resuscitating trauma patients, the evidence is still not robust. The quality of evidence was primarily downgraded by the limited number of included studies and great heterogeneity and severe risk of bias in these. Further studies are strongly recommended.

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.

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