Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR201210000441277 Date of Approval: 24/10/2012
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Clinical Randomisation of an Antifibrinolytic in Significant Head Injury (CRASH-3)
Official scientific title Tranexamic acid for the treatment of significant traumatic brain injury: an international randomised, double blind placebo controlled trial
Brief summary describing the background and objectives of the trial Worldwide, over 10 million people are killed or hospitalised because of traumatic brain injury (TBI) each year. About 90% of deaths from TBI occur in low and middle income countries. The CRASH-3 trial will provide reliable evidence about the effect of tranexamic acid on mortality and disability in patients with traumatic brain injury. The effect of tranexamic acid on the risk of vascular occlusive events and seizures will also be assessed.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) CRASH 3
Disease(s) or condition(s) being studied Injury, Occupational Diseases, Poisoning,Nervous System Diseases,Traumatic Brain Injury
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Other
Anticipated trial start date 01/09/2011
Actual trial start date 20/07/2012
Anticipated date of last follow up 28/01/2017
Actual Last follow-up date
Anticipated target sample size (number of participants) 10000
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32233-0/fulltext?dgcid=raven_jbs_etoc_email
Secondary Ids Issuing authority/Trial register
NCT01402882 CLINICALTRIALS.GOV
2011-003669-14 European Union Drug Regulating Authorities Clinical Trials (EUDRACT )
ISRCTN15088122 International Standard Randomised Controlled Trial Number Register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Permuted block randomisation. Treatment packs containing TXA and placebo will be packed in balanced blocks of 8 (4 TXA: 4 Placebo) into a box in random order Randomisation codes will be generated and secured by an independent statistical consultant from Sealed Envelope Ltd (UK). Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Tranexamic Acid (TXA) A total of 2 grams of tranexamic acid will be used in this trial. A fixed dose of 1 gram loading dose of tranexamic acid followed by a 1 gram maintenance dose. loading dose 1 gram over 10 minutes then infusion of 1 gram over 8 hours 1 gram TXA Added to 100 mL sodium chloride 0.9% and infused over 10 minutes and then 1 gram of TXA Added to 500 mL of any isotonic intravenous solution and infused at 120 mg/hr [60 mL/hr] for about 8 hours 5000 Placebo
Control Group Sodium chloride 0.9% A total of 2 grams of will be used in this trial. A fixed dose of 1 gram loading dose of tranexamic acid followed by a 1 gram maintenance dose. loading dose 1 gram over 10 minutes then infusion of 1 gram over 8 hours 1 gram added to 100 mL sodium chloride 0.9% and infused over 10 minutes and then 1 gram of TXA Added to 500 mL of any isotonic intravenous solution and infused at 120 mg/hr [60 mL/hr] for about 8 hours 5000 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Adult 2. Traumatic brain injury 3. Within 8 hours of injury 4. Any intracranial bleeding on CT scan OR a GCS of 12 or less 5. No significant extra-cranial haemorrhage 6. Where the responsible clinician is substantially uncertain as to the appropriateness of antifibrinolytic agents in the patient The fundamental eligibility criterion is the responsible clinician's 'uncertainty' as to whether or not to use an antifibrinolytic agent in a particular patient with traumatic brain injury 16 Year(s) 150 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 17/11/2011 London School of Hygiene and Tropical Medicine Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Keppel Street London WC1E 7HT United Kingdom
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Death in hospital within 28 days of injury (cause of death will be described) 28 days post randomisation
Secondary Outcome 1. Vascular occlusive events (myocardial infarction, stroke, pulmonary embolism, clinical evidence of deep vein thrombosis) 2. Disability assessed using the Disability Rating Scale and Patient Orientated Outcomes 3. Seizures 4. Neurosurgical intervention 5. Days in intensive care The outcome is collected at death, discharge or 28 days after randomisation, whichever occurs first.
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Obafemi Awolowo University Teaching Hospitals Complex Ile-Ife Nigeria
University of Nigeria Teaching Hospital Ituku-Ozalla Enugu, Enugu State Nigeria
National Coordinator University College Hospital Ibadan Ibadan, Oyo State, Nigeria
CRASH-3 is an international trial. Please see http://crash3.lshtm.ac.uk/index.php/collaborators/ for a full list of collaborators
FUNDING SOURCES
Name of source Street address City Postal code Country
1. London School of Hygiene and Tropical Medicine (United Kingdom) Keppel Street London WC1E 7HT United Kingdom
2. J P Moulton Charitable Foundation United Kingdom
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor 1. London School of Hygiene and Tropical Medicine (United Kingdom) Keppel Street London WC1E 7HT United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
Professor Temitayo Shokunbi Ibadan, Oyo State, Nigeria
Dr Tamar Gogichaishvili High Technology Medical Center, University Clinic Tbilisi 0144 Georgia
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Ian Roberts crash@lshtm.ac.uk +44 (0)20 7299 4684 Keppel Street
City Postal code Country Position/Affiliation
London WC1E 7HT United Kingdom Professor of Epidemiology
Role Name Email Phone Street address
Public Enquiries Haleema Shakur crash@lshtm.ac.uk +44 (0)20 7299 4684 Keppel Street
City Postal code Country Position/Affiliation
London WC1E 7HT United Kingdom Project Director
Role Name Email Phone Street address
Scientific Enquiries Haleema Shakur crash@lshtm.ac.uk +44 (0)20 7299 4684 Keppel Street
City Postal code Country Position/Affiliation
London WC1E 7HT United Kingdom Project Director
REPORTING
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URL Results Available Results Summary Result Posting Date First Journal Publication Date
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Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information