CRASH-2 Trial Research Articles

Tranexamic acid in trauma

Napolitano, Lena M. MD; Cohen, Mitchell J. MD; Cotton, Bryan A. MD, MPH; Schreiber, Martin A. MD; Moore, Ernest E. MD Author Information

The CRASH-2 trial: a randomised controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients

Among trauma patients who survive to reach hospital, exsanguination is a common cause of death. A widely practicable treatment that reduces blood loss after trauma could prevent thousands of premature deaths each year. The CRASH-2 trial aimed to determine the effect of the early administration of tranexamic acid on death and transfusion requirement in bleeding trauma patients. In addition, the effort of tranexamic acid on the risk of vascular occlusive events was assessed. Tranexamic acid (TXA) reduces bleeding in patients undergoing elective surgery. We assessed the effects and cost-effectiveness of the early administration of a short course of TXA on death, vascular occlusive events and the receipt of blood transfusion in trauma patients. Randomised placebo-controlled trial and economic evaluation. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight, generated with a computer random number generator. Both participants and study staff (site investigators and trial co-ordinating centre staff) were masked to treatment allocation. All analyses were by intention to treat. A Markov model was used to assess cost-effectiveness. The health outcome was the number of life-years (LYs) gained. Cost data were obtained from hospitals, the World Health Organization database and UK reference costs. Cost-effectiveness was measured in international dollars ($) per LY. Deterministic and probabilistic sensitivity analyses were performed to test the robustness of the results to model assumptions. Two hundred and seventy-four hospitals in 40 countries. Adult trauma patients (n = 20,211) with, or at risk of, significant bleeding who were within 8 hours of injury. Tranexamic acid (loading dose 1 g over 10 minutes then infusion of 1 g over 8 hours) or matching placebo. The primary outcome was death in hospital within 4 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. Patients were allocated to TXA (n = 10,096) and to placebo (n = 10,115), of whom 10,060 and 10,067 patients, respectively, were analysed. All-cause mortality at 28 days was significantly reduced by TXA [1463 patients (14.5%) in the TXA group vs 1613 patients (16.0%) in the placebo group; relative risk (RR) 0.91; 95% confidence interval (CI) 0.85 to 0.97; p = 0.0035]. The risk of death due to bleeding was significantly reduced [489 patients (4.9%) died in the TXA group vs 574 patients (5.7%) in the placebo group; RR 0.85; 95% CI 0.76 to 0.96; p = 0.0077]. We recorded strong evidence that the effect of TXA on death due to bleeding varied according to the time from injury to treatment (test for interaction p < 0.0001). Early treatment (≤ 1 hour from injury) significantly reduced the risk of death due to bleeding [198 out of 3747 patients (5.3%) died in the TXA group vs 286 out of 3704 patients (7.7%) in the placebo group; RR 0.68; 95% CI 0.57 to 0.82; p < 0.0001]. Treatment given between 1 and 3 hours also reduced the risk of death due to bleeding [147 out of 3037 patients (4.8%) died in the TXA group vs 184 out of 2996 patients (6.1%) in the placebo group; RR 0.79; 95% CI 0.64 to 0.97; p = 0.03]. Treatment given after 3 hours seemed to increase the risk of death due to bleeding [144 out of 3272 patients (4.4%) died in the TXA group vs 103 out of 3362 patients (3.1%) in the placebo group; RR 1.44; 95% CI1.12 to 1.84; p = 0.004]. We recorded no evidence that the effect of TXA on death due to bleeding varied by systolic blood pressure, Glasgow Coma Scale score or type of injury. Administering TXA to bleeding trauma patients within 3 hours of injury saved an estimated 755 LYs per 1000 trauma patients in the UK. The cost of giving TXA to 1000 patients was estimated at $30,830. The incremental cost of giving TXA compared with not giving TXA was $48,002. The incremental cost per LY gained of administering TXA was $64. Early administration of TXA safely reduced the risk of death in bleeding trauma patients and is highly cost-effective. Treatment beyond 3 hours of injury is unlikely to be effective. Future work [the Clinical Randomisation of an Antifibrinolytic in Significant Head injury-3 (CRASH-3) trial] will evaluate the effectiveness and safety of TXA in the treatments of isolated traumatic brain injury (http://crash3.lshtm.ac.uk/). Current Controlled Trials ISRCTN86750102, ClinicalTrials.gov NCT00375258 and South African Clinical Trial Register DOH-27-0607-1919. The project was funded by the Bupa Foundation, the J P Moulton Charitable Foundation and the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 10. See HTA programme website for further project information.

Tranexamic acid in remote damage control resuscitation

With the advent of remote damage control resuscitation and far-forward surgery, a renewed emphasis has been placed on examining a variety of pharmacologic adjuncts to controlling blood loss before definitive operative intervention. In this paper, the authors review the current state of the art for tranexamic acid (TXA) and its potential benefits to those patients who are in need of a massive transfusion. Specifically addressed are its biologic and pharmacologic properties, as well the results of a number of recent studies. The 2010 CRASH-2 trial randomized in excess of 20,000 patients and demonstrated a reduction in all-cause mortality from 16.0 to 14.5% and death due to bleeding from 5.7 to 4.9%. The 2012 Military Application of Tranexamic Acid in Trauma Emergency Resuscitation study provided a retrospective analysis of 896 wounded cared for at a military hospital in Afghanistan. This study demonstrated a 23.9%-17.4% reduction in all-cause mortality. Finally, they discuss the potential complications associated with TXA use as well as areas of future research, which are needed to solidify our knowledge of TXA and its potential beneficial effects on controlling bleeding.

Risk factors for vascular occlusive events and death due to bleeding in trauma patients; an analysis of the CRASH-2 cohort.

BackgroundVascular occlusive events can complicate recovery following trauma. We examined risk factors for venous and arterial vascular occlusive events in trauma patients and the extent to which the risk of vascular occlusive events varies with the severity of bleeding.Methods and FindingsWe conducted a cohort analysis using data from a large international, double-blind, randomised, placebo-controlled trial (The CRASH-2 trial) [1]. We studied the association between patient demographic and physiological parameters at hospital admission and the risk of vascular occlusive events. To assess the extent to which risk of vascular occlusive events varies with severity of bleeding, we constructed a prognostic model for the risk of death due to bleeding and assessed the relationship between risk of death due to bleeding and risk of vascular occlusive events. There were 20,127 trauma patients with outcome data including 204 (1.01%) patients with a venous event (pulmonary embolism or deep vein thrombosis) and 200 (0.99%) with an arterial event (myocardial infarction or stroke). There were 81 deaths due to vascular occlusive events. Increasing age, decreasing systolic blood pressure, increased respiratory rates, longer central capillary refill times, higher heart rates and lower Glasgow Coma Scores (all p<0.02) were strong risk factors for venous and arterial vascular occlusive events. Patients with more severe bleeding as assessed by predicted risk of haemorrhage death had a greatly increased risk for all types of vascular occlusive event (all p<0.001).ConclusionsPatients with severe traumatic bleeding are at greatly increased risk of venous and arterial vascular occlusive events. Older age and blunt trauma are also risk factors for vascular occlusive events. Effective treatment of bleeding may reduce venous and arterial vascular occlusive complications in trauma patients.

Military medical revolution

Abstract : The battlefield has seen tremendous revolutions in military medical affairs (RMMAs) as a result of the last decade of continuous combat operations. The advances in deployed and en route combat casualty care are categorized as individual RMMAs shown in Table 1. As with prehospital advances, the basis for many of the RMMAs in the deployed hospital care environment as well as en route care was translated from civilian trauma practice but is realistic and relevant to the battlefield context. As the conflict evolved, the substantive data from the battlefield led to many new paradigms of treatment and evacuation. The successful implementation of many of these battlefield practices was then effectively translated back into the civilian injury care environment as has been typical of medical advances developed subsequent to previous conflicts of antiquity. The RMMAs that occurred during the last 10 years of combat casualty care are in the realm of deployed hospital care and en route care and are discussed in detail in this article.

Tranexamic Acid Lowers Risk of Death from Traumatic Bleeding

Results of the CRASH-2 trial suggest that tranexamic acid reduces mortality without increasing risk of thrombosis in adult patients with traumatic

Effect of tranexamic acid on mortality in patients with traumatic bleeding: prespecified analysis of data from randomised controlled trial

Objectives To examine whether the effect of tranexamic acid on the risk of death and thrombotic events in patients with traumatic bleeding varies according to baseline risk of death. To...

Predicting early death in patients with traumatic bleeding: development and validation of prognostic model

Objective To develop and validate a prognostic model for early death in patients with traumatic bleeding.Design Multivariable logistic regression of a large international cohort of trauma patients.Setting 274 hospitals in...

CRASH-3 - tranexamic acid for the treatment of significant traumatic brain injury: study protocol for an international randomized, double-blind, placebo-controlled trial

BackgroundWorldwide, over 10 million people are killed or hospitalized because of traumatic brain injury each year. About 90% of deaths occur in low- and middle-income countries. The condition mostly affects young adults, and many experience long lasting or permanent disability. The social and economic burden is considerable. Tranexamic acid (TXA) is commonly given to surgical patients to reduce bleeding and the need for blood transfusion. It has been shown to reduce the number of patients receiving a blood transfusion by about a third, reduces the volume of blood transfused by about one unit, and halves the need for further surgery to control bleeding in elective surgical patients.Methods/designThe CRASH-3 trial is an international, multicenter, pragmatic, randomized, double-blind, placebo-controlled trial to quantify the effects of the early administration of TXA on death and disability in patients with traumatic brain injury. Ten thousand adult patients who fulfil the eligibility criteria will be randomized to receive TXA or placebo. Adults with traumatic brain injury, who are within 8 h of injury and have any intracranial bleeding on computerized tomography (CT scan) or Glasgow Coma Score (GCS) of 12 or less can be included if the responsible doctor is substantially uncertain as to whether or not to use TXA in this patient. Patients with significant extracranial bleeding will be excluded since there is evidence that TXA improves outcome in these patients. Treatment will entail a 1 g loading dose followed by a 1 g maintenance dose over 8 h.The main analyses will be on an ‘intention-to-treat’ basis, irrespective of whether the allocated treatment was received. Results will be presented as appropriate effect estimates with a measure of precision (95% confidence intervals). Subgroup analyses for the primary outcome will be based on time from injury to randomization, the severity of the injury, location of the bleeding, and baseline risk. Interaction tests will be used to test whether the effect of treatment differs across these subgroups. A study with 10,000 patients will have approximately 90% power to detect a 15% relative reduction from 20% to 17% in all-cause mortality.Trial registrationCurrent Controlled Trials ISRCTN15088122; Clinicaltrials.gov NCT01402882

Avoidable mortality from giving tranexamic acid to bleeding trauma patients: an estimation based on WHO mortality data, a systematic literature review and data from the CRASH-2 trial

BackgroundThe CRASH-2 trial showed that early administration of tranexamic acid (TXA) safely reduces mortality in bleeding in trauma patients. Based on data from the CRASH-2 trial, global mortality data and a systematic literature review, we estimated the number of premature deaths that might be averted every year worldwide through the use of TXA.MethodsWe used CRASH-2 trial data to examine the effect of TXA on death due to bleeding by geographical region. We used WHO mortality data (2008) and data from a systematic review of the literature to estimate the annual number of in-hospital trauma deaths due to bleeding. We then used the relative risk estimates from the CRASH-2 trial to estimate the number of premature deaths that could be averted if all hospitalised bleeding trauma patients received TXA within one hour of injury, and within three hours of injury. Sensitivity analyses were used to explore the effect of uncertainty in the parameter estimates and the assumptions made in the model.ResultsThere is no evidence that the effect of TXA on death due to bleeding varies by geographical region (heterogeneity p = 0.70). Based on WHO data and our systematic literature review, we estimate that each year worldwide there are approximately 400,000 in-hospital trauma deaths due to bleeding. If patients received TXA within one hour of injury then approximately 128,000 (uncertainty range [UR] ≈ 72,000 to 172,000) deaths might be averted. If patients received TXA within three hours of injury then approximately 112,000 (UR ≈ 68,000 to 148,000) deaths might be averted. Country specific estimates show that the largest numbers of deaths averted would be in India and China.ConclusionsThe use of TXA in the treatment of traumatic bleeding has the potential to prevent many premature deaths every year. A large proportion of the potential health gains are in low and middle income countries.

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.

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). 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. 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. 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 Tobón Uribe, Hospital Universitario San José de Popayán and Fundación Valle del Lili. 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. Participants were randomly allocated to receive either a loading dose of 1 g of TXA infused over 10 minutes followed by an intravenous infusion of 1 g over 8 hours or matching placebo. 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. 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). 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. Current Controlled Trials ISRCTN86750102. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 13. See the HTA programme website for further project information.

Cost-Effectiveness Analysis of Administering Tranexamic Acid to Bleeding Trauma Patients Using Evidence from the CRASH-2 Trial

ObjectiveTo assess the cost effectiveness of giving tranexamic acid (TXA) to bleeding trauma patients in low, middle and high income settings.MethodsThe 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 ($) per LY. Both deterministic and probabilistic sensitivity analyses were performed to test the robustness of the results to model assumptions.FindingsAdministering TXA to bleeding trauma patients within three hours of injury saved an estimated 372, 315 and 755 LYs per 1,000 trauma patients in Tanzania, India and the UK respectively. The cost of giving TXA to 1,000 patients was $17,483 in Tanzania, $19,550 in India and $30,830 in the UK. The incremental cost of giving TXA versus not giving TXA was $18,025 in Tanzania, $20,670 in India and $48,002 in the UK. The estimated incremental cost per LY gained of administering TXA is $48, $66 and $64 in Tanzania, India and the UK respectively.ConclusionEarly administration of TXA to bleeding trauma patients is likely to be highly cost effective in low, middle and high income settings.Trial RegistrationThis paper uses data collected by the CRASH 2 trial: Controlled-Trials.com ISRCTN86750102, Clinicaltrials.gov NCT00375258 and South African Clinical Trial Register DOH-27-0607-1919.

Tranexamic Acid for Traumatic Hemorrhage: Best Given Within 1 Hour

In the CRASH-2 trial (JW Emerg Med Jun 15 2010), of 20,211 adult trauma patients with (or at risk for) hemorrhage who were randomized to receive

The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial

The aim of the CRASH-2 trial was to assess the effects of early administration of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage. Tranexamic acid significantly reduced all-cause mortality. Because tranexamic acid is thought to exert its effect through inhibition of fibrinolysis, we undertook exploratory analyses of its effect on death due to bleeding. The CRASH-2 trial was undertaken in 274 hospitals in 40 countries. 20,211 adult trauma patients with, or at risk of, significant bleeding were randomly assigned within 8 h of injury to either tranexamic acid (loading dose 1 g over 10 min followed by infusion of 1 g over 8 h) or placebo. Patients were randomly assigned by selection of the lowest numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Both participants and study staff (site investigators and trial coordinating centre staff ) were masked to treatment allocation. We examined the effect of tranexamic acid on death due to bleeding according to time to treatment, severity of haemorrhage as assessed by systolic blood pressure, Glasgow coma score (GCS), and type of injury. All analyses were by intention to treat. The trial is registered as ISRCTN86750102, ClinicalTrials.gov NCT00375258, and South African Clinical Trial Register/Department of Health DOH-27-0607-1919. 10,096 patients were allocated to tranexamic acid and 10,115 to placebo, of whom 10,060 and 10,067, respectively, were analysed. 1063 deaths (35%) were due to bleeding. We recorded strong evidence that the effect of tranexamic acid on death due to bleeding varied according to the time from injury to treatment (test for interaction p<0.0001). Early treatment (≤1 h from injury) significantly reduced the risk of death due to bleeding (198/3747 [5.3%] events in tranexamic acid group vs 286/3704 [7.7%] in placebo group; relative risk [RR] 0.68, 95% CI 0.57-0.82; p<0.0001). Treatment given between 1 and 3 h also reduced the risk of death due to bleeding (147/3037 [4.8%] vs 184/2996 [6.1%]; RR 0.79, 0.64-0.97; p=0.03). Treatment given after 3 h seemed to increase the risk of death due to bleeding (144/3272 [4.4%] vs 103/3362 [3.1%]; RR 1.44, 1.12-1.84; p=0.004). We recorded no evidence that the effect of tranexamic acid on death due to bleeding varied by systolic blood pressure, Glasgow coma score, or type of injury. Tranexamic acid should be given as early as possible to bleeding trauma patients. For trauma patients admitted late after injury, tranexamic acid is less effective and could be harmful. UK NIHR Health Technology Assessment programme, Pfizer, BUPA Foundation, and J P Moulton Charitable Foundation.

Tranexamic acid for trauma

After its publication in July, 2010, the CRASH-2 study 1 CRASH-2 trial collaboratorsEffects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010; 376: 23-32 Summary Full Text Full Text PDF PubMed Scopus (2053) Google Scholar generated widespread interest in the early administration of the antifibrinolytic agent tranexamic acid to patients with traumatic bleeding. Tranexamic acid is an inexpensive, easily used, and relatively safe drug, and it seemed to have saved lives. However, how it did so was unclear—the blood-transfusion requirements of the tranexamic acid and placebo groups were similar and, survival bias notwithstanding, the mortality benefit might have been attributable to an effect of tranexamic acid on something other than acute traumatic coagulopathy. 2 Levy J Antifibrinolytic therapy: new data and new concepts. Lancet. 2010; 376: 3-4 Summary Full Text Full Text PDF PubMed Scopus (86) Google Scholar Effect of consent rituals on mortality in emergency care researchClinical trials are important in improving the safety and effectiveness of emergency care. Many such trials seek to assess the effects of time-critical treatments for life-threatening disorders such as traumatic brain injury, severe haemorrhage, or respiratory distress. In general, before patients can be enrolled in such trials, current regulations require that they or their legal representatives provide written informed consent.1,2 Although the requirement for written informed consent can sometimes be waived3—eg, if the patient is unconscious, treatment is urgent, and no relative is available—written consent is usually required in emergency-care research, despite the delays to treatment that this will usually entail. Full-Text PDF The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trialTranexamic acid should be given as early as possible to bleeding trauma patients. For trauma patients admitted late after injury, tranexamic acid is less effective and could be harmful. Full-Text PDF

Reducing the environmental impact of trials: a comparison of the carbon footprint of the CRASH-1 and CRASH-2 clinical trials

BackgroundAll 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.MethodsWe 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.ResultsThe 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).ConclusionsFaster 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 NumbersCRASH-1: ISRCTN74459797CRASH-2: ISRCTN86750102

Ensayo clínico Prágmatico en trauma: el estudio Crash-2 en el Perú

CRASH-2 is a pragmatic clinical trial which evaluates the efficacy of a widely available, low cost antifibrinolytic for the prevention of mortality and bleeding in patients with trauma. In this article we present some issues related to the magnitude of the problem as well as the need for research in trauma relevant to the Peruvian context. The rationale for the CRASH-2 trial and the Peruvian experience up to date are also discussed.

Improving the evidence base for trauma care: progress in the international CRASH-2 trial.

Improving the evidence base for trauma care: progress in the international CRASH-2 trial.

Antifibrinolytic agents in traumatic haemorrhage.

This article is an invitation to doctors around the world to participate in the CRASH-2 trial (Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage), a large, multi-centre, randomised controlled trial of a simple and widely practicable treatment for traumatic hemorrhage. The rationale for the trial and contact details for those who would like to take part are given below. Evidence from randomised controlled trials is essential for improving health care. In the case of widely practicable treatments for common health problems, even modest treatment effects can result in substantial health gains. However, to detect such modest effects requires large multi-centre randomised trials involving hundreds of collaborating health professionals internationally. Many health professionals would be pleased to collaborate in such trials if they knew that they were underway, but at present there is no easy way to bring these trials to their attention. Three years ago, in the context of the CRASH-1 trial (Corticosteroid Randomisation After Significant Head Injury), the trial investigators sent a message to the electronic mailing list of the World Association of Medical Editors, asking them to consider publishing an editorial about the CRASH-1 trial that invited doctors around the world to participate. In response to this request, many medical journals around the world published the CRASH-1 trial editorial in various different languages, and as a result, many more doctors joined the CRASH-1 trial. The trial was completed in May 2004 and involved around 400 hospitals in almost 50 countries, and because of its size provided a reliable answer to an important question (see www.crash.lshtm.ac.uk). This current article is being published as the result of a similar such request to medical editors in the context of the CRASH-2 trial.

Antifibrinolytic agents in traumatic haemorrhage

This article is an invitation to doctors around the world to participate in the CRASH-2 trial (Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage), a large, multi-centre, randomised controlled trial of a simple and widely practicable treatment for traumatic hemorrhage. The rationale for the trial and contact details for those who would like to take part are given below. Evidence from randomised controlled trials is essential for improving health care. In the case of widely practicable treatments for common health problems, even modest treatment effects can result in substantial health gains. However, to detect such modest effects requires large multi-centre randomised trials involving hundreds of collaborating health professionals internationally. Many health professionals would be pleased to collaborate in such trials if they knew that they were underway, but at present there is no easy way to bring these trials to their attention. Three years ago, in the context of the CRASH-1 trial (Corticosteroid Randomisation After Significant Head Injury), the trial investigators sent a message to the electronic mailing list of the World Association of Medical Editors, asking them to consider publishing an editorial about the CRASH-1 trial that invited doctors around the world to participate. In response to this request, many medical journals around the world published the CRASH-1 trial editorial in various different languages, and as a result, many more doctors joined the CRASH-1 trial. The trial was completed in May 2004 and involved around 400 hospitals in almost 50 countries, and because of its size provided a reliable answer to an important question (see www.crash.lshtm.ac.uk). This current article is being published as the result of a similar such request to medical editors in the context of the CRASH-2 trial.