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Prehospital use of plasma in traumatic hemorrhage (The PUPTH Trial): study protocol for a randomised controlled trial.

ABSTRACT: Severe traumatic injury and haemorrhagic shock are frequently associated with disruptions of coagulation function (such as trauma-induced coagulopathy TIC) and activation of inflammatory cascades. These pathologies may be exacerbated by current standard of care resuscitation protocols. Observational studies suggest early administration of plasma to severely-injured haemorrhaging patients may correct TIC, minimise inflammation, and improve survival. The proposed randomised clinical trial will evaluate the clinical effectiveness of pre-hospital plasma administration compared with standard- of-care crystalloid resuscitation in severely-injured patients with major traumatic haemorrhage.This is a prospective, randomized, open-label, non-blinded trial to determine the effect of pre-hospital administration of thawed plasma (TP) on mortality, morbidity, transfusion requirements, coagulation, and inflammatory response in severely-injured bleeding trauma patients. Two hundred and ten eligible adult trauma patients will be randomised to receive either two units of plasma, to be administered in-field, vs standard of care normal saline (NS). Main analyses will compare subjects allocated to TP to those allocated to NS, on an intention-to-treat basis. Primary outcome measure is all-cause 30-day mortality. Secondary outcome measures include coagulation and lipidomic/pro-inflammatory marker responses, volume of resuscitation fluids (crystalloid, colloid) and blood products administered, and major hospital outcomes (e.g. incidence of MSOF, length of ICU stay, length of hospital stay).This study is part of a US Department of Defense (DoD)-funded multi-institutional investigation, conducted independently of, but in parallel with, the University of Pittsburgh and University of Denver. Demonstration of significant reductions in mortality and coagulopathic/inflammatory-related morbidities as a result of pre-hospital plasma administration would be of considerable clinical importance for the management of haemorrhagic shock in both civilian and military populations.ClinicalTrials.gov: NCT02303964 on 28 November 2014.

SUBMITTER: Reynolds PS

PROVIDER: S-EPMC4518517 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Prehospital use of plasma in traumatic hemorrhage (The PUPTH Trial): study protocol for a randomised controlled trial.

Reynolds Penny S PS Michael Mary Jane MJ Cochran Emily D ED Wegelin Jacob A JA Spiess Bruce D BD

Trials 20150730

<h4>Background</h4>Severe traumatic injury and haemorrhagic shock are frequently associated with disruptions of coagulation function (such as trauma-induced coagulopathy TIC) and activation of inflammatory cascades. These pathologies may be exacerbated by current standard of care resuscitation protocols. Observational studies suggest early administration of plasma to severely-injured haemorrhaging patients may correct TIC, minimise inflammation, and improve survival. The proposed randomised clin ...[more]

PMID: 26220293

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Project description:BackgroundIntracranial hemorrhage occurs in over 60% of severe head injuries in one of three types: extradural (EDH); subdural (SDH); and intraparenchymal (TICH). Prompt surgical removal of significant SDH and EDH is established and widely accepted. However, TICH is more common and is found in more than 40% of severe head injuries. It is associated with a worse outcome but the role for surgical removal remains undefined. Surgical practice in the treatment of TICHs differs widely around the world. The aim of early surgery in TICH removal is to prevent secondary brain injury. There have been trials of surgery for spontaneous ICH (including the STICH II trial), but none so far of surgery for TICH.Methods/designThe UK National Institutes of Health Research has funded STITCH(Trauma) to determine whether a policy of early surgery in patients with TICH improves outcome compared to a policy of initial conservative treatment. It will include a health economics component and carry out a subgroup analysis of patients undergoing invasive monitoring. This is an international multicenter pragmatic randomized controlled trial.Patients are eligible if: they are within 48 h of injury; they have evidence of TICH on CT scan with a confluent volume of attenuation significantly raised above that of the background white and grey matter that has a total volume >10 mL; and their treating neurosurgeon is in equipoise.Patients will be ineligible if they have: a significant surface hematoma (EDH or SDH) requiring surgery; a hemorrhage/contusion located in the cerebellum; three or more separate hematomas fulfilling inclusion criteria; or severe pre-existing physical or mental disability or severe co-morbidity which would lead to poor outcome even if the patient made a full recovery from the head injury.Patients will be randomized via an independent service. Patients randomized to surgery receive surgery within 12 h. Both groups will be monitored according to standard neurosurgical practice. All patients have a CT scan at 5 days (+/-2 days) to assess changes in hematoma size. Follow-up is by postal questionnaire at 6 and 12 months. The recruitment target is 840 patients.Trial registrationCurrent Controlled Trials ISRCTN19321911.

Project description:BackgroundTraumatic brain injury is a leading cause of death and disability worldwide. Laboratory and clinical studies demonstrate a possible beneficial effect of erythropoietin in improving outcomes in the traumatic brain injury cohort. However, there are concerns regarding the association of erythropoietin and thrombosis in the critically ill. A large-scale, multi-centre, blinded, parallel-group, placebo-controlled, randomised trial is currently underway to address this hypothesis.Methods/designThe erythropoietin in traumatic brain injury trial is a stratified prospective, multi-centre, randomised, blinded, parallel-group, placebo-controlled phase III trial. It aims to determine whether the administration of erythropoietin compared to placebo improves neurological outcome in patients with moderate or severe traumatic brain injury at six months after injury. The trial is designed to recruit 606 patients between 15 and 65 years of age with severe (Glasgow Coma Score: 3 to 8) or moderate (Glasgow Coma Score: 9 to 12) traumatic brain injury in Australia, New Zealand, Kingdom of Saudi Arabia, France, Finland, Germany and Ireland. Trial patients will receive either subcutaneous erythropoietin or placebo within 24 hours of injury, and weekly thereafter for up to three doses during the intensive care unit admission. The primary outcome will be the combined proportion of unfavourable neurological outcomes at six months: severe disability or death. Secondary outcomes will include the rate of proximal deep venous thrombosis detected by compression Doppler ultrasound, six-month mortality, the proportion of patients with composite vascular events (deep venous thrombosis, pulmonary embolism, myocardial infarction, cardiac arrest and cerebrovascular events) at six months and quality of life with health economic evaluations.DiscussionWhen completed, the trial aims to provide evidence on the efficacy and safety of erythropoietin in traumatic brain injury patients, and to provide clear guidance for clinicians in their management of this devastating condition.Trial registrationAustralian New Zealand Clinical Trials registry: ACTRN12609000827235 (registered on 22 September 2009). Clinicaltrials.gov: NCT00987454 (registered on 29 September 2009). European Drug Regulatory Authorities Clinical Trials: 2011-005235-22 (registered on 18 January 2012).

Project description:IntroductionIndividuals with moderate-severe traumatic brain injury (m-sTBI) experience progressive brain and behavioural declines in the chronic stages of injury. Longitudinal studies found that a majority of patients with m-sTBI exhibit significant hippocampal atrophy from 5 to 12 months post-injury, associated with decreased cognitive environmental enrichment (EE). Encouragingly, engaging in EE has been shown to lead to neural improvements, suggesting it is a promising avenue for offsetting hippocampal neurodegeneration in m-sTBI. Allocentric spatial navigation (ie, flexible, bird's eye view approach), is a good candidate for EE in m-sTBI because it is associated with hippocampal activation and reduced ageing-related volume loss. Efficacy of EE requires intensive daily training, prohibitive within most current health delivery systems. The present protocol is a novel, remotely delivered and self-administered intervention designed to harness principles from EE and allocentric spatial navigation to offset hippocampal atrophy and potentially improve hippocampal functions such as navigation and memory for patients with m-sTBI.Methods and analysisEighty-four participants with chronic m-sTBI are being recruited from an urban rehabilitation hospital and randomised into a 16-week intervention (5?hours/week; total: 80?hours) of either targeted spatial navigation or an active control group. The spatial navigation group engages in structured exploration of different cities using Google Street View that includes daily navigation challenges. The active control group watches and answers subjective questions about educational videos. Following a brief orientation, participants remotely self-administer the intervention on their home computer. In addition to feasibility and compliance measures, clinical and experimental cognitive measures as well as MRI scan data are collected pre-intervention and post-intervention to determine behavioural and neural efficacy.Ethics and disseminationEthics approval has been obtained from ethics boards at the University Health Network and University of Toronto. Findings will be presented at academic conferences and submitted to peer-reviewed journals.Trial registration numberVersion 3, ClinicalTrials.gov Registry (NCT04331392).

Project description:IntroductionHaemorrhage causes most preventable prehospital trauma deaths and about a third of in-hospital trauma deaths. Tranexamic acid (TXA), administered soon after hospital arrival in certain trauma systems, is an effective therapy in preventing or managing acute traumatic coagulopathy. However, delayed administration of TXA appears to be ineffective or harmful. The effectiveness of prehospital TXA, incidence of thrombotic complications, benefit versus risk in advanced trauma systems and the mechanism of benefit remain uncertain.Methods and analysisThe Pre-hospital Anti-fibrinolytics for Traumatic Coagulopathy and Haemorrhage (The PATCH-Trauma study) is comparing TXA, initiated prehospital and continued in hospital over 8 hours, with placebo in patients with severe trauma at risk of acute traumatic coagulopathy. We present the trial protocol and an overview of the statistical analysis plan. There will be 1316 patients recruited by prehospital clinicians in Australia, New Zealand and Germany. The primary outcome will be the eight-level Glasgow Outcome Scale Extended (GOSE) at 6 months after injury, dichotomised to favourable (GOSE 5-8) and unfavourable (GOSE 1-4) outcomes, analysed using an intention-to-treat (ITT) approach. Secondary outcomes will include mortality at hospital discharge and at 6 months, blood product usage, quality of life and the incidence of predefined adverse events.Ethics and disseminationThe study was approved by The Alfred Hospital Research and Ethics Committee in Victoria and also approved in New South Wales, Queensland, South Australia, Tasmania and the Northern Territory. In New Zealand, Northern A Health and Disability Ethics Committee provided approval. In Germany, Witten/Herdecke University has provided ethics approval. The PATCH-Trauma study aims to provide definitive evidence of the effectiveness of prehospital TXA, when used in conjunction with current advanced trauma care, in improving outcomes after severe injury.Trial registration numberNCT02187120.

Project description:BackgroundTraumatic brain injury (TBI) is a major public health concern and many people develop long-lasting physical and neuropsychiatric consequences following a TBI. Despite the emphasis on physical rehabilitation, it is the emotional and behavioural consequences that have greater impact on people with TBI and their families. One such problem behaviour is aggression which can be directed towards others, towards property or towards the self. Aggression is reported to be common after TBI (37-71%) and causes major stress for patients and their families. Both drug and non-drug interventions are used to manage this challenging behaviour, but the evidence-base for these interventions is poor and no drugs are currently licensed for the treatment of aggression following TBI. The most commonly used drugs for this purpose are antipsychotics, particularly second-generation drugs such as risperidone. Despite this widespread use, randomised controlled trials (RCTs) of antipsychotic drugs, including risperidone, have not been conducted. We have, therefore, set out to test the feasibility of conducting an RCT of this drug for people who have aggressive behaviour following TBI.Methods/designWe will examine the feasibility of conducting a placebo-controlled, double-blind RCT of risperidone for the management of aggression in adults with TBI and also assess participants' views about their experience of taking part in the study. We will randomise 50 TBI patients from secondary care services in four centres in London and Kent to up to 4 mg of risperidone orally or an inert placebo and follow them up 12 weeks later. Participants will be randomised to active or control treatment in a 1:1 ratio via an external and remote web-based randomisation service. Participants will be assessed at baseline and 12-week follow-up using a battery of assessment scales to measure changes in aggressive behaviour (MOAS, IRQ) as well as global functioning (GOS-E, CGI), quality of life (EQ-5D-5L, SF-12) and mental health (HADS). We will also assess the adverse effect profile with a standard scale (UKU) and collect available data from medical records on blood tests (serum glucose/HbA1c, lipid profile, prolactin), and check body weight and blood pressure. In addition completion of the MOAS and a check for any new or worsening side-effect will be completed weekly and used by the prescribing clinician to determine continuing dosage. Family carers' wellbeing will be assessed with CWSQ. Service use will be recorded using CSRI. A process evaluation will be carried out at the end of the trial using both qualitative and quantitative methodology.DiscussionAggressive behaviour causes immense distress among some people with TBI and their families. By examining the feasibility of a double-blind, placebo-controlled RCT, we aim to discover whether this approach can successfully be used to test the effects of risperidone for the treatment of aggressive behaviour among people with aggression following TBI and improve the evidence base for the treatment of these symptoms. Our criteria for demonstrating success of the feasibility study are: (1) recruitment of at least 80% of the study sample, (2) uptake of intervention by at least 80% of participants in the active arm of the trial and (3) completion of follow-up interviews at 12 weeks by at least 75% of the study participants.Trial registrationISRCTN30191436 . Registered on 19 December 2016.

Project description:BACKGROUND:Despite evidence from clinical trials that intravenous (IV) thrombolysis is a cost-effective treatment for selected acute ischaemic stroke patients, there remain large variations in the rate of IV thrombolysis delivery between stroke services. This study is evaluating whether an enhanced care pathway delivered by paramedics (the Paramedic Acute Stroke Treatment Assessment (PASTA)) could increase the number of patients who receive IV thrombolysis treatment. METHODS:Study design: Cluster randomised trial with economic analysis and parallel process evaluation. SETTING:National Health Service ambulance services, emergency departments and hyper-acute stroke units within three geographical regions of England and Wales. Randomisation: Ambulance stations within each region are the units of randomisation. According to station allocation, paramedics based at a station deliver the PASTA pathway (intervention) or continue with standard stroke care (control). Study intervention: The PASTA pathway includes structured pre-hospital information collection, prompted pre-notification, structured handover of information in hospital and assistance with simple tasks during the initial hospital assessment. Study-trained intervention group paramedics deliver this pathway to adults within 4 h of suspected stroke onset. Study control: Standard stroke care according to national and local guidelines for the pre-hospital and hospital assessment of suspected stroke. PARTICIPANTS:Participants enrolled in the study are adults with confirmed stroke who were assessed by a study paramedic within 4 h of symptom onset. PRIMARY OUTCOME:Proportion of participants receiving IV thrombolysis. SAMPLE SIZE:1297 participants provide 90% power to detect a 10% difference in the proportion of patients receiving IV thrombolysis. DISCUSSION:The results from this trial will determine whether an enhanced care pathway delivered by paramedics can increase thrombolysis delivery rates. TRIAL REGISTRATION:ISRCTN registry, ISRCTN12418919 . Registered on 5 November 2015.

Project description:IntroductionStroke is the leading cause of death and disability in China. The median time of stroke pre-hospital delay is more than 15 hours, mainly due to the lack of awareness on stroke symptoms and calling emergency services. We developed Stroke 1-2-0 recognition tool in China, by adapting Face, Arm, Speech and Time. Our preliminary findings suggested that Stroke 1-2-0 can improve public's knowledge of the stroke symptoms, but its impact on the prehospital delay is still unclear. Furthermore, these findings were mainly obtained from Shanghai, one of the largest metropolises in China. However, more than half of population in China lives in the rural area. Given the striking disparities in socioeconomic status and quality of stroke care across the nation, a multicentre trial is warranted.Methods and analysisStroke 1-2-0 education programme will adopt a multicentre, cluster-randomised controlled design. We aimed to recruit 32 communities from 16 counties across China. Each county includes two communities having more than 100 000 residents. The two communities sampled in the same county will be randomly assigned to receive either Stroke 1-2-0 education programme or usual care. The primary objective of this study is to evaluate the impact of Stroke 1-2-0 public education programme in reducing stroke prehospital delay among adults residing in the community, compared with the usual care. The intervention will be implemented for 1 year. The primary outcomes are the symptom onset to hospital arrival time ('onset-to-door time', ODT) and 3-hour hospital arriving rate. We will use an intention-to-treat approach. A linear mixed model will be used to control for potential cluster effects.Ethics and disseminationThis study is approved by the Shanghai Minhang District Central Hospital Institutional Review Board (Shanghai, China). The findings will be disseminated via peer-reviewed publications and conference presentations.Trial registration numberChiCTR2000040782.

Project description:BackgroundMild traumatic brain injury (mTBI) is an acknowledged public health problem. Up to 25% of adult with mTBI present persistent symptoms. Headache, dizziness, nausea and neck pain are the most commonly reported symptoms and are frequently associated with cervical spine and vestibular impairments. The most recent international consensus statement (2017 Berlin consensus) recommends the addition of an individualized rehabilitation approach for mTBI with persistent symptoms. The addition of an individualized rehabilitation approach including the evaluation and treatment of cervical and vestibular impairments leading to symptoms such as neck pain, headache and dizziness is, however, recommended based only on limited scientific evidence. The benefit of such intervention should therefore be further investigated.ObjectiveTo compare the addition of a 6-week individualized cervicovestibular rehabilitation program to a conventional approach of gradual sub-threshold physical activation (SPA) alone in adults with persistent headache, neck pain and/or dizziness-related following a mTBI on the severity of symptoms and on other indicators of clinical recovery. We hypothesize that such a program will improve all outcomes faster than a conventional approach (between-group differences at 6-week and 12-week).MethodsIn this single-blind, parallel-group randomized controlled trial, 46 adults with subacute (3 to12 weeks post-injury) persistent mTBI symptoms will be randomly assigned to: 1) a 6-week SPA program or 2) SPA combined with a cervicovestibular rehabilitation program. The cervicovestibular rehabilitation program will include education, cervical spine manual therapy and exercises, vestibular rehabilitation and home exercises. All participants will take part in 4 evaluation sessions (baseline, week 6, 12 and 26) performed by a blinded evaluator. The primary outcome will be the Post-Concussion Symptoms Scale. The secondary outcomes will be time to clearance to return to function, number of recurrent episodes, Global Rating of Change, Numerical Pain Rating Scale, Neck Disability Index, Headache Disability Inventory and Dizziness Handicap Inventory. A 2-way ANOVA and an intention-to-treat analysis will be used.DiscussionControlled trials are needed to determine the best rehabilitation approach for mTBI with persistent symptoms such as neck pain, headache and dizziness. This RCT will be crucial to guide future clinical management recommendations.Trial registrationClinicalTrials.gov Identifier - NCT03677661, Registered on September, 15th 2018.

Dataset Information

Prehospital use of plasma in traumatic hemorrhage (The PUPTH Trial): study protocol for a randomised controlled trial.

Publications

Prehospital use of plasma in traumatic hemorrhage (The PUPTH Trial): study protocol for a randomised controlled trial.

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