scholarly journals Tranexamic acid to improve functional status in adults with spontaneous intracerebral haemorrhage: the TICH-2 RCT

2019 ◽  
Vol 23 (35) ◽  
pp. 1-48 ◽  
Author(s):  
Nikola Sprigg ◽  
Katie Flaherty ◽  
Jason P Appleton ◽  
Rustam Al-Shahi Salman ◽  
Daniel Bereczki ◽  
...  
Keyword(s):  
Tranexamic Acid ◽  
Functional Status ◽  
Intracerebral Haemorrhage ◽  
Primary Outcome ◽  
Exclusion Criteria ◽  
Treatment Groups ◽  
Haematoma Expansion ◽  
The Uk ◽  
Future Work ◽  
Spontaneous Intracerebral Haemorrhage

Background Tranexamic acid reduces death due to bleeding after trauma and postpartum haemorrhage. Objective The aim of the study was to assess if tranexamic acid is safe, reduces haematoma expansion and improves outcomes in adults with spontaneous intracerebral haemorrhage (ICH). Design The TICH-2 (Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage) study was a pragmatic, Phase III, prospective, double-blind, randomised placebo-controlled trial. Setting Acute stroke services at 124 hospitals in 12 countries (Denmark, Georgia, Hungary, Ireland, Italy, Malaysia, Poland, Spain, Sweden, Switzerland, Turkey and the UK). Participants Adult patients (aged ≥ 18 years) with ICH within 8 hours of onset. Exclusion criteria Exclusion criteria were ICH secondary to anticoagulation, thrombolysis, trauma or a known underlying structural abnormality; patients for whom tranexamic acid was thought to be contraindicated; prestroke dependence (i.e. patients with a modified Rankin Scale [mRS] score > 4); life expectancy < 3 months; and a Glasgow Coma Scale score of < 5. Interventions Participants, allocated by randomisation, received 1 g of an intravenous tranexamic acid bolus followed by an 8-hour 1-g infusion or matching placebo (i.e. 0.9% saline). Main outcome measure The primary outcome was functional status (death or dependency) at day 90, which was measured by the shift in the mRS score, using ordinal logistic regression, with adjustment for stratification and minimisation criteria. Results A total of 2325 participants (tranexamic acid, n = 1161; placebo, n = 1164) were recruited from 124 hospitals in 12 countries between 2013 and 2017. Treatment groups were well balanced at baseline. The primary outcome was determined for 2307 participants (tranexamic acid, n = 1152; placebo, n = 1155). There was no statistically significant difference between the treatment groups for the primary outcome of functional status at day 90 [adjusted odds ratio (aOR) 0.88, 95% confidence interval (CI) 0.76 to 1.03; p = 0.11]. Although there were fewer deaths by day 7 in the tranexamic acid group (aOR 0.73, 95% CI 0.53 to 0.99; p = 0.041), there was no difference in case fatality at 90 days (adjusted hazard ratio 0.92, 95% CI 0.77 to 1.10; p = 0.37). Fewer patients experienced serious adverse events (SAEs) after treatment with tranexamic acid than with placebo by days 2 (p = 0.027), 7 (p = 0.020) and 90 (p = 0.039). There was no increase in thromboembolic events or seizures. Limitations Despite attempts to enrol patients rapidly, the majority of participants were enrolled and treated > 4.5 hours after stroke onset. Pragmatic inclusion criteria led to a heterogeneous population of participants, some of whom had very large strokes. Although 12 countries enrolled participants, the majority (82.1%) were from the UK. Conclusions Tranexamic acid did not affect a patient’s functional status at 90 days after ICH, despite there being significant modest reductions in early death (by 7 days), haematoma expansion and SAEs, which is consistent with an antifibrinolytic effect. Tranexamic acid was safe, with no increase in thromboembolic events. Future work Future work should focus on enrolling and treating patients early after stroke and identify which participants are most likely to benefit from haemostatic therapy. Large randomised trials are needed. Trial registration Current Controlled Trials ISRCTN93732214. Funding This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 35. See the NIHR Journals Library website for further project information. The project was also funded by the Pragmatic Trials, UK, funding call and the Swiss Heart Foundation in Switzerland.

scholarly journals Tranexamic acid for acute intracerebral haemorrhage growth based on imaging assessment (TRAIGE): a multicentre, randomised, placebo-controlled trial

2021 ◽  
pp. svn-2021-000942
Author(s):  
Jingyi Liu ◽  
Ximing Nie ◽  
Hongqiu Gu ◽  
Qi Zhou ◽  
Haixin Sun ◽  
...  
Keyword(s):  
Placebo Group ◽  
Tranexamic Acid ◽  
Intracerebral Haemorrhage ◽  
Intracranial Haemorrhage ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Intracerebral Haematoma ◽  
Spot Sign ◽  
Double Blind ◽  
Risk Of Death

BackgroundStudies show tranexamic acid can reduce the risk of death and early neurological deterioration after intracranial haemorrhage. We aimed to assess whether tranexamic acid reduces haematoma expansion and improves outcome in intracerebral haemorrhage patients susceptible to haemorrhage expansion.MethodsWe did a prospective, double-blind, randomised, placebo-controlled trial at 10 stroke centres in China. Acute supratentorial intracerebral haemorrhage patients were eligible if they had indication of haemorrhage expansion on admission imaging (eg, spot sign, black hole sign or blend sign), and were treatable within 8 hours of symptom onset. Patients were randomly assigned (1:1) to receive either tranexamic acid or a matching placebo. The primary outcome was intracerebral haematoma growth (>33% relative or >6 mL absolute) at 24 hours. Clinical outcomes were assessed at 90 days.ResultsOf the 171 included patients, 124 (72.5%) were male, and the mean age was 55.9±11.6 years. 89 patients received tranexamic acid and 82 received placebo. The primary outcome did not differ significantly between the groups: 36 (40.4%) patients in the tranexamic acid group and 34 (41.5%) patients in the placebo group had intracranial haemorrhage growth (OR 0.96, 95% CI 0.52 to 1.77, p=0.89). The proportion of death was lower in the tranexamic acid treatment group than placebo group (8.1% vs 10.0%), but there were no significant differences in secondary outcomes including absolute intracranial haemorrhage growth, death and dependency.ConclusionsAmong patients susceptible to haemorrhage expansion treated within 8 hours of stroke onset, tranexamic acid did not significantly prevent intracerebral haemorrhage growth. Larger studies are needed to assess safety and efficacy of tranexamic acid in intracerebral haemorrhage patients.

scholarly journals Does tranexamic acid lead to changes in MRI measures of brain tissue health in patients with spontaneous intracerebral haemorrhage? Protocol for a MRI substudy nested within the double-blind randomised controlled TICH-2 trial

BMJ Open ◽  
2018 ◽  
Vol 8 (2) ◽  
pp. e019930 ◽  
Author(s):  
Rob A Dineen ◽  
Stefan Pszczolkowski ◽  
Katie Flaherty ◽  
Zhe K Law ◽  
Paul S Morgan ◽  
...  
Keyword(s):  
Tranexamic Acid ◽  
Intracerebral Haemorrhage ◽  
Lesion Volume ◽  
Imaging Data ◽  
Double Blind ◽  
Link Type ◽  
Diffusion Weighted ◽  
Primary Hypothesis ◽  
Randomised Controlled ◽  
Spontaneous Intracerebral Haemorrhage

ObjectivesTo test whether administration of the antifibrinolytic drug tranexamic acid (TXA) in patients with spontaneous intracerebral haemorrhage (SICH) leads to increased prevalence of diffusion-weighted MRI-defined hyperintense ischaemic lesions (primary hypothesis) or reduced perihaematomal oedema volume, perihaematomal diffusion restriction and residual MRI-defined SICH-related tissue damage (secondary hypotheses).DesignMRI substudy nested within the double-blind randomised controlled Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage (TICH)-2 trial (ISRCTN93732214).SettingInternational multicentre hospital-based study.ParticipantsEligible adults consented and randomised in the TICH-2 trial who were also able to undergo MRI scanning. To address the primary hypothesis, a sample size of n=280 will allow detection of a 10% relative increase in prevalence of diffusion-weighted imaging (DWI) hyperintense lesions in the TXA group with 5% significance, 80% power and 5% imaging data rejection.InterventionsTICH-2 MRI substudy participants will undergo MRI scanning using a standardised protocol at day ~5 and day ~90 after randomisation. Clinical assessments, randomisation to TXA or placebo and participant follow-up will be performed as per the TICH-2 trial protocol.ConclusionThe TICH-2 MRI substudy will test whether TXA increases the incidence of new DWI-defined ischaemic lesions or reduces perihaematomal oedema or final ICH lesion volume in the context of SICH.Ethics and disseminationThe TICH-2 trial obtained ethical approval from East Midlands - Nottingham 2 Research Ethics Committee (12/EM/0369) and an amendment to allow the TICH-2 MRI sub study was approved in April 2015 (amendment number SA02/15). All findings will be published in peer-reviewed journals. The primary outcome results will also be presented at a relevant scientific meeting.Trial registration numberISRCTN93732214; Pre-results.

051 Systematic review of CT angiographic ‘spot sign’ for predicting mortality

2018 ◽  
Vol 89 (6) ◽  
pp. A21.2-A21
Author(s):  
Natasha Krishnadas ◽  
Thanh G Phan ◽  
Vivian WY Lai ◽  
Michael J Batt ◽  
Ronil V Chandra ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Outcome Measures ◽  
Intracerebral Haemorrhage ◽  
Clinical Utility ◽  
Limited Data ◽  
Likelihood Ratios ◽  
Spot Sign ◽  
Haematoma Expansion ◽  
Available Information ◽  
Spontaneous Intracerebral Haemorrhage

IntroductionTo study whether presence of the CT angiographic ‘spot sign’ for spontaneous intracerebral haemorrhage (ICH) expansion is predictive of mortality.MethodPubMed, Medline, conference proceedings and manuscript references up to June 2017 were searched for studies reporting “computed tomography angiography” and “spot sign” or “intracerebral haemorrhage” and “spot sign”. Positive (PLR) and negative (NLR) likelihood ratios were calculated using MetaDisc. The PLR needs to be ≥5 and NLR ≤0.1 for a test to be clinically useful.ResultsThere have not been previous systematic reviews correlating the spot sign to clinical outcome. There were 36 studies describing 6888 patients and 32 clinical outcome measures. However, there were only three outcome measures with sufficient comparability across the studies. PLR, and NLR for in-hospital mortality by spot sign were 2.47 (95% CI 1.59–3.82) and 0.62 (95%CI 0.46–0.82) with a plateau of 2.7 and 0.6 respectively across 10 studies. PLR and NLR for 3 month mortality by haematoma expansion were 0.41 (95%CI 0.35–0.47) and 0.8 (95%CI 0.78–0.83) with a plateau of 2.0 and 0.8 respectively across 8 studies.ConclusionOverall, there is limited data available on clinical outcomes stratified by the ‘spot sign’. Based on the available information, the PLR and NLR did not meet respective thresholds of 5 and 0.1 required to have clinical utility.

scholarly journals Risks of recurrent stroke and all serious vascular events after spontaneous intracerebral haemorrhage: pooled analyses of two population-based studies

2021 ◽  
Vol 20 (6) ◽  
pp. 437-447 ◽  
Author(s):  
Linxin Li ◽  
Michael T C Poon ◽  
Neshika E Samarasekera ◽  
Luke A Perry ◽  
Tom J Moullaali ◽  
...  
Keyword(s):  
Intracerebral Haemorrhage ◽  
Recurrent Stroke ◽  
Population Based ◽  
Vascular Events ◽  
Spontaneous Intracerebral Haemorrhage

scholarly journals Exenatide once weekly over 2 years as a potential disease-modifying treatment for Parkinson’s disease: protocol for a multicentre, randomised, double blind, parallel group, placebo controlled, phase 3 trial: The ‘Exenatide-PD3’ study

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e047993
Author(s):  
Nirosen Vijiaratnam ◽  
Christine Girges ◽  
Grace Auld ◽  
Marisa Chau ◽  
Kate Maclagan ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Primary Outcome ◽  
Phase 3 ◽  
Double Blind ◽  
Treatment Groups ◽  
Link Type ◽  
South Central ◽  
Disease Modifying ◽  
Secondary Outcomes

IntroductionParkinson’s disease (PD) is a common neurodegenerative disorder with substantial morbidity. No disease-modifying treatments currently exist. The glucagon like peptide-1 receptor agonist exenatide has been associated in single-centre studies with reduced motor deterioration over 1 year. The aim of this multicentre UK trial is to confirm whether these previous positive results are maintained in a larger number of participants over 2 years and if effects accumulate with prolonged drug exposure.Methods and analysisThis is a phase 3, multicentre, double-blind, randomised, placebo-controlled trial of exenatide at a dose of 2 mg weekly in 200 participants with mild to moderate PD. Treatment duration is 96 weeks. Randomisation is 1:1, drug to placebo. Assessments are performed at baseline, week 12, 24, 36, 48, 60, 72, 84 and 96 weeks.The primary outcome is the comparison of Movement Disorders Society Unified Parkinson’s Disease Rating Scale part 3 motor subscore in the practically defined OFF medication state at 96 weeks between participants according to treatment allocation. Secondary outcomes will compare the change between groups among other motor, non-motor and cognitive scores. The primary outcome will be reported using descriptive statistics and comparisons between treatment groups using a mixed model, adjusting for baseline scores. Secondary outcomes will be summarised between treatment groups using summary statistics and appropriate statistical tests to assess for significant differences.Ethics and disseminationThis trial has been approved by the South Central-Berkshire Research Ethics Committee and the Health Research Authority. Results will be disseminated in peer-reviewed journals, presented at scientific meetings and to patients in lay-summary format.Trial registration numbersNCT04232969, ISRCTN14552789.

scholarly journals Validation of the BATT score for prehospital risk stratification of traumatic haemorrhagic death: usefulness for tranexamic acid treatment criteria

2021 ◽  
Vol 29 (1) ◽  
Author(s):  
Francois-Xavier Ageron ◽  
Timothy J. Coats ◽  
Vincent Darioli ◽  
Ian Roberts
Keyword(s):  
Tranexamic Acid ◽  
Acid Treatment ◽  
Injury Severity ◽  
External Validation ◽  
Research Network ◽  
Brier Score ◽  
Trauma Patients ◽  
Using Data ◽  
The Uk ◽  
The Impact

Abstract Background Tranexamic acid reduces surgical blood loss and reduces deaths from bleeding in trauma patients. Tranexamic acid must be given urgently, preferably by paramedics at the scene of the injury or in the ambulance. We developed a simple score (Bleeding Audit Triage Trauma score) to predict death from bleeding. Methods We conducted an external validation of the BATT score using data from the UK Trauma Audit Research Network (TARN) from 1st January 2017 to 31st December 2018. We evaluated the impact of tranexamic acid treatment thresholds in trauma patients. Results We included 104,862 trauma patients with an injury severity score of 9 or above. Tranexamic acid was administered to 9915 (9%) patients. Of these 5185 (52%) received prehospital tranexamic acid. The BATT score had good accuracy (Brier score = 6%) and good discrimination (C-statistic 0.90; 95% CI 0.89–0.91). Calibration in the large showed no substantial difference between predicted and observed death due to bleeding (1.15% versus 1.16%, P = 0.81). Pre-hospital tranexamic acid treatment of trauma patients with a BATT score of 2 or more would avoid 210 bleeding deaths by treating 61,598 patients instead of avoiding 55 deaths by treating 9915 as currently. Conclusion The BATT score identifies trauma patient at risk of significant haemorrhage. A score of 2 or more would be an appropriate threshold for pre-hospital tranexamic acid treatment.

scholarly journals National survey of feasibility of NIV trials for management of children with bronchiolitis

2020 ◽  
Vol 4 (1) ◽  
pp. e000780
Author(s):  
Anna Rosala-Hallas ◽  
Ashley P Jones ◽  
Emma Bedson ◽  
Vanessa Compton ◽  
Ricardo M Fernandes ◽  
...  
Keyword(s):  
National Survey ◽  
Controlled Trial ◽  
Management Strategies ◽  
Eligibility Criteria ◽  
Training Requirements ◽  
Non Invasive Ventilation ◽  
Respiratory Management ◽  
Randomised Controlled ◽  
The Uk ◽  
Future Work

BackgroundBronchiolitis is a major cause of admission to hospital in children. Non-invasive ventilation (NIV) support with continuous positive airway pressure (CPAP) or high-flow nasal cannula (HFNC) oxygen is routinely used for infants in the UK with bronchiolitis.ObjectiveTo establish UK paediatric practice regarding management of bronchiolitis, and to explore issues pertinent to the design of a potential future randomised controlled trial of NIV.DesignScreening logs were completed in hospitals in England capturing information on paediatric bronchiolitis admissions. An online national survey of clinical practice was disseminated to healthcare professionals (HCPs) across the UK to ascertain current management strategies.ResultsScreening logs captured data on 393 infants from 8 hospitals. Reasons for admission were most commonly respiratory distress and/or poor fluid intake. Oxygen was administered for 54% of admissions. Respiratory (CPAP and HFNC) and non-respiratory support administered varied considerably. The national survey was completed by 111 HCPs from 76 hospitals. Data were obtained on criteria used to commence and wean NIV, responsibilities for altering NIV settings, minimum training requirements for staff managing a child on NIV, and numbers of trained staff. Most centres were interested in and capable of running a trial of NIV, even out of normal office hours.ConclusionsRespiratory and non-respiratory management of bronchiolitis in UK centres varies widely. A trial of HFNC oxygen therapy in this group of patients is feasible and HCPs would be willing to randomise patients into such a trial. Future work should focus on defining trial eligibility criteria.

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