64 research outputs found
Cost-effectiveness analysis of administering tranexamic acid to bleeding trauma patients using evidence from the CRASH-2 trial.
No full textOBJECTIVE: To assess the cost effectiveness of giving tranexamic acid (TXA) to bleeding trauma patients in low, middle and high income settings. METHODS: The CRASH-2 trial showed that TXA administration reduces the risk of death in bleeding trauma patients with a small but statistically significant increase in non-intensive care stay. A Markov model was used to assess the cost effectiveness of TXA in Tanzania, India and the United Kingdom (UK). The health outcome was the number of life years gained (LYs). Two costs were considered: the cost of administering TXA and the cost of additional days in hospital. Cost data were obtained from hospitals, World Health Organization (WHO) database and UK reference costs. Cost-effectiveness was measured in international dollars (17,483 in Tanzania, 30,830 in the UK. The incremental cost of giving TXA versus not giving TXA was 20,670 in India and 48, 64 in Tanzania, India and the UK respectively. CONCLUSION: Early administration of TXA to bleeding trauma patients is likely to be highly cost effective in low, middle and high income settings. TRIAL REGISTRATION: This paper uses data collected by the CRASH 2 trial: Controlled-Trials.com ISRCTN86750102, Clinicaltrials.govNCT00375258 and South African Clinical Trial Register DOH-27-0607-1919
Reducing the environmental impact of trials: a comparison of the carbon footprint of the CRASH-1 and CRASH-2 clinical trials.
No full textBACKGROUND: All sectors of the economy, including the health research sector, must reduce their carbon emissions. The UK National Institute for Health Research has recently prepared guidelines on how to minimize the carbon footprint of research. We compare the carbon emissions from two international clinical trials in order to identify where emissions reductions can be made. METHODS: We conducted a carbon audit of two clinical trials (the CRASH-1 and CRASH-2 trials), quantifying the carbon dioxide emissions produced over a one-year audit period. Carbon emissions arising from the coordination centre, freight delivery, trial-related travel and commuting were calculated and compared. RESULTS: The total emissions in carbon dioxide equivalents during the one-year audit period were 181.3 tonnes for CRASH-1 and 108.2 tonnes for CRASH-2. In total, CRASH-1 emitted 924.6 tonnes of carbon dioxide equivalents compared with 508.5 tonnes for CRASH-2. The CRASH-1 trial recruited 10,008 patients over 5.1 years, corresponding to 92 kg of carbon dioxide per randomized patient. The CRASH-2 trial recruited 20,211 patients over 4.7 years, corresponding to 25 kg of carbon dioxide per randomized patient. The largest contributor to emissions in CRASH-1 was freight delivery of trial materials (86.0 tonnes, 48% of total emissions), whereas the largest contributor in CRASH-2 was energy use by the trial coordination centre (54.6 tonnes, 30% of total emissions). CONCLUSIONS: Faster patient recruitment in the CRASH-2 trial largely accounted for its greatly increased carbon efficiency in terms of emissions per randomized patient. Lighter trial materials and web-based data entry also contributed to the overall lower carbon emissions in CRASH-2 as compared to CRASH-1. TRIAL REGISTRATION NUMBERS: CRASH-1: ISRCTN74459797CRASH-2: ISRCTN86750102
The CRASH trial protocol (Corticosteroid randomisation after significant head injury) [ISRCTN74459797].
No full textBACKGROUND: Worldwide, millions of people are treated each year for significant head injury. A substantial proportion die, and many more are disabled. If short term corticosteroid infusion could be reliably shown to reduce these risks by just a few percent then this might affect the treatment of a few hundred thousand patients a year, protecting thousands from death or long term disability. STUDY DESIGN: CRASH is a large simple, placebo-controlled trial of the effects of a 48-hour infusion of corticosteroids on death and on neurological disability, among adults with head injury and some impairment of consciousness. Head injured patients with impaired consciousness who are judged to be 16 years or older are eligible if the responsible doctor is, for any reason, substantially uncertain whether or not to use corticosteroids. ORGANISATION: The CRASH trial will determine reliably the effects on death and disability of a short corticosteroid infusion following significant head injury. To detect or refute improvements of only a few percent in outcome, many thousands of acute head injury patients must be randomised between control and steroid infusions. Such large numbers will be possible only if hundreds of doctors and nurses can collaborate in the participating emergency departments. Since they are busy, and working in emergency situations, the trial involves them in almost no extra work: no special investigations or changes to usual management are required, and data collection is absolutely minimal. The trial is on-going and new collaborators are welcome. Further information about the trial is available at http://www.crash.lshtm.ac.u
CRASH-2 (Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage) intracranial bleeding study: the effect of tranexamic acid in traumatic brain injury - a nested, randomised, placebo-controlled trial
No full textBackground: Tranexamic acid (TXA) has been shown to reduce blood loss in surgical patients and the risk of death in patients with traumatic bleeding, with no apparent increase in vascular occlusive events. These findings raise the possibility that it might also be effective in traumatic brain injury (TBI). Objective: The Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage Intracranial Bleeding Study (CRASH-2 IBS) was conducted to quantify the effect of an early short course of TXA on intracranial haemorrhage and new focal cerebral ischaemic lesions in patients with TBI. Design: CRASH-2 IBS was a prospective randomised controlled trial nested within the CRASH-2 trial. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight. We used a local pack system that selected the lowest numbered treatment pack from a box containing eight numbered packs. Apart from the pack number, the treatment packs were identical. The pack number was recorded on the entry form, which was sent to the international trial co-ordinating centre in London, UK. Once the treatment pack number was recorded, the patient was included in the trial whether or not the treatment pack was opened or the allocated treatment started. All site investigators and trial co-ordinating centre staff were masked to treatment allocation. Setting: Ten hospitals: (India) Aditya Neuroscience Centre, Sanjivani Hospital, CARE Hospital, Christian Medical College, Medical Trust Hospital, Jeevan Jyoti Hospital and (Colombia) Hospital Universitario San Vicente de Paul, Hospital Pablo Tobon Uribe, Hospital Universitario San Jose de Popayan and Fundacion Valle del Lili. Participants: The trial was conducted in a subset of 270 CRASH-2 trial participants. Patients eligible for inclusion in the CRASH-2 IBS fulfilled the inclusion criteria for the CRASH-2 trial, and also had TBI [Glasgow Coma Scale score of <= 14 and a brain computerised tomography (CT) scan compatible with TBI]. Pregnant women and patients for whom a second brain CT scan was not possible were excluded. Interventions: Participants were randomly allocated to receive either a loading dose of 1g of TXA infused over 10 minutes followed by an intravenous infusion of 1g over 8 hours or matching placebo. Main outcome measure: The primary outcome was the increase in size of intracranial haemorrhage growth between a CT scan at hospital admission and a second scan 24-48 hours later. Results: One hundred and thirty-three patients were allocated to TXA and 137 to placebo, of whom information on the primary (imaging) outcome was available for 123 (92%) and 126 (92%) respectively. The analysis suggested that TXA was likely to be associated with a reduction in haemorrhage growth [adjusted difference -3.8 ml, 95% credibility interval (CrI) -11.5 ml to 3.9 ml], fewer focal ischaemic lesions [adjusted odds ratio (OR) 0.54, 95% CrI 0.20 to 1.46] and fewer deaths (adjusted OR 0.49, 95% CrI 0.22 to 1.06). Conclusions: This was the first randomised controlled study to evaluate the effect of TXA in TBI patients and it found that neither moderate benefits nor moderate harmful effects can be excluded. However, although uncertainty remains, our analyses suggest that TXA administration might improve outcome in TBI patients and provide grounds for evaluating this hypothesis in future research
CRASH-2 - Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage
No full textA large randomised placebo controlled trial among trauma patients with or at risk of significant haemorrhage, of the effects of antifibrinolytic treatment on death and transfusion requirement. CRASH-2 is a randomised, controlled, double-blind trial undertaken in 274 hospitals in 40 countries. A total of 20211 adult trauma patients, with, or at risk of, significant bleeding (haemorrhage) were randomly assigned within 8 hours of injury to either tranexamic acid (TXA) or matching placebo. The primary outcome was death in hospital within four weeks of injury and was described with the following categories: bleeding, vascular occlusion (myocardial infarction, stroke and pulmonary embolism), multiorgan failure, head injury, and other
CRASH - Corticosteroid Randomisation after Significant Head Injury
No full textA large simple placebo controlled trial, among adults with head injury and impaired consciousness, of the effects of a 48-hour infusion of corticosteroids on death and neurological disability. CRASH was a randomised, controlled, double-blind trial undertaken in 239 hospitals in 49 countries. A total of 10008 adults with head injury and a Glasgow Coma Score (GCS) of 14 or less within 8 hours of injury were randomly allocated 48 hour infusion of corticosteroids (methylprednisolone) or placebo. Primary outcomes were death within 2 weeks of injury or disability at 6 months. Prespecified subgroup analyses were based on injury severity (GCS) at randomisation and on time from injury to randomisation and analysis was by intention to treat
Improving the evidence base for trauma care: progress in the international CRASH-2 trial.
No full textThe added value of ordinal analysis in clinical trials: an example in traumatic brain injury.
No full textINTRODUCTION: In clinical trials, ordinal outcome measures are often dichotomized into two categories. In traumatic brain injury (TBI) the 5-point Glasgow outcome scale (GOS) is collapsed into unfavourable versus favourable outcome. Simulation studies have shown that exploiting the ordinal nature of the GOS increases chances of detecting treatment effects. The objective of this study is to quantify the benefits of ordinal analysis in the real-life situation of a large TBI trial. METHODS: We used data from the CRASH trial that investigated the efficacy of corticosteroids in TBI patients (n = 9,554). We applied two techniques for ordinal analysis: proportional odds analysis and the sliding dichotomy approach, where the GOS is dichotomized at different cut-offs according to baseline prognostic risk. These approaches were compared to dichotomous analysis. The information density in each analysis was indicated by a Wald statistic. All analyses were adjusted for baseline characteristics. RESULTS: Dichotomous analysis of the six-month GOS showed a non-significant treatment effect (OR = 1.09, 95% CI 0.98 to 1.21, P = 0.096). Ordinal analysis with proportional odds regression or sliding dichotomy showed highly statistically significant treatment effects (OR 1.15, 95% CI 1.06 to 1.25, P = 0.0007 and 1.19, 95% CI 1.08 to 1.30, P = 0.0002), with 2.05-fold and 2.56-fold higher information density compared to the dichotomous approach respectively. CONCLUSIONS: Analysis of the CRASH trial data confirmed that ordinal analysis of outcome substantially increases statistical power. We expect these results to hold for other fields of critical care medicine that use ordinal outcome measures and recommend that future trials adopt ordinal analyses. This will permit detection of smaller treatment effects
Tranexamic acid in traumatic brain injury: an explanatory study nested within the CRASH-3 trial.
No full textPURPOSE: The CRASH-3 trial is a randomised trial of tranexamic acid (TXA) on death and disability in patients with traumatic brain injury (TBI). It is based on the hypothesis that early TXA treatment can prevent deaths from post-traumatic intracranial bleeding. The results showed that timely TXA treatment reduces head injury deaths in patients with reactive pupils and those with a mild to moderate GCS at baseline. We examined routinely collected CT scans in a sample of 1767 CRASH-3 trial patients to explore if, why, and how patients are affected by TXA. METHODS: The CRASH-3 IBMS is an explanatory study nested within the CRASH-3 trial. We measured the volume of intracranial bleeding on CT scans using established methods (e.g. ABC/2). RESULTS: Patients with any un-reactive pupil had a median intracranial bleeding volume of 60 ml (IQR 18-101 ml) and patients with reactive pupils had a median volume of 26 ml (IQR 1-55 ml). Patients with severe GCS had median intracranial bleeding volume of 37 ml (IQR 3-75 ml) and patients with moderate to mild GCS had a median volume of 26 ml (IQR 0.4-50 ml). For every hour increase from injury to the baseline scan, the risk of new bleeding on a further scan decreased by 12% (adjusted RR = 0.88 [95% CI 0.80-0.96], p = 0.0047). CONCLUSION: Patients with reactive pupils and/or mild to moderate GCS may have benefited from TXA in the CRASH-3 trial because they had less intracranial bleeding at baseline. However, because bleeding occurs soon after injury, treatment delay reduces the benefit of TXA
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