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Trial record 1 of 1 for:    NCT01402882
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Clinical Randomisation of an Antifibrinolytic in Significant Head Injury (CRASH-3)

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ClinicalTrials.gov Identifier: NCT01402882
Recruitment Status : Active, not recruiting
First Posted : July 26, 2011
Last Update Posted : March 14, 2019
Sponsor:
Information provided by (Responsible Party):
London School of Hygiene and Tropical Medicine

Tracking Information
First Submitted Date  ICMJE July 25, 2011
First Posted Date  ICMJE July 26, 2011
Last Update Posted Date March 14, 2019
Actual Study Start Date  ICMJE July 2012
Estimated Primary Completion Date September 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 8, 2016)
The primary outcome is death in hospital in patients recruited within 3 hours and cause of death will be described. [ Time Frame: within 28 days of injury ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 25, 2011)
The primary outcome is death in hospital and cause of death will be described. [ Time Frame: within 28 days of injury ]
Change History Complete list of historical versions of study NCT01402882 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 25, 2011)
  • (a) Vascular occlusive events (myocardial infarction, stroke, pulmonary embolism, clinical evidence of deep vein thrombosis) [ Time Frame: Prior death, discharge or 28 days ]
  • (b) In hospital disability assessed using the Disability Rating Scale and Patient Orientated Outcome [ Time Frame: Prior death, discharge or 28 days ]
  • (c) Seizures [ Time Frame: Prior death, discharge or day 28 ]
  • (d) Neurosurgical intervention [ Time Frame: prior death, discharge or day 28 ]
  • (e) Days in intensive care [ Time Frame: prior death, discharge or day 28 ]
  • (f) Other adverse events [ Time Frame: prior death, discharge or day 28 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: December 19, 2016)
  • CRASH-3 IBS: Primary outcome - the total volume of intracranial haemorrhage [ Time Frame: 1) CT scan done before receipt of trial treatment; (2) CT scan done after receipt of trial treatment (up to 28 days after randomisation) ]
  • Frequency of progressive haemorrhage: number of patients with a post-randomisation CT scan with total haemorrhage volume of more than 25% of the volume on the pre-randomisation scan [ Time Frame: 1) CT scan done before receipt of trial treatment; (2) CT scan done after receipt of trial treatment (up to 28 days after randomisation) ]
  • Frequency of delayed haemorrhage: [ Time Frame: 1) CT scan done before receipt of trial treatment; (2) CT scan done after receipt of trial treatment (up to 28 days after randomisation) ]
  • New focal ischaemic lesions: [ Time Frame: 1) CT scan done before receipt of trial treatment; (2) CT scan done after receipt of trial treatment (up to 28 days after randomisation) ]
  • • Total volume of intracranial bleeding in patients who undergo surgical evacuation of haemorrhage after randomisation [ Time Frame: 1) CT scan done before receipt of trial treatment; (2) CT scan done after receipt of trial treatment (up to 28 days after randomisation) ]
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Clinical Randomisation of an Antifibrinolytic in Significant Head Injury
Official Title  ICMJE Tranexamic Acid for the Treatment of Significant Traumatic Brain Injury: an International Randomised, Double Blind Placebo Controlled Trial
Brief Summary 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. Additionally, a nested study will be conducted in a subset of CRASH-3 trial participants. This nested study (CRASH-3 Intracranial Bleeding Sub-Study [CRASH-3 IBS]) will examine the effect of tranexamic acid on intracranial haemorrhage and cerebral ischaemia using CT Scans in approximately 1,000 patients randomised into the CRASH-3 trial.
Detailed Description

BACKGROUND: 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. TBI mostly affects young adults and many experiencing long lasting or permanent disability. The social and economic burden of TBI is considerable. Tranexamic acid (TXA) is commonly given to surgical patients to reduce bleeding and the need for blood transfusion. TXA 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. More recently, the CRASH-2 trial showed that the administration of TXA within 8 hours of injury significantly reduces deaths due to bleeding (RR=0.85, 95% CI 0.76-0.96; p=0.008), and all-cause mortality (RR=0.91, 95% CI 0.85-0.97; p=0.0035), with no apparent increase in vascular occlusive events. A meta-analysis of randomised controlled trials of TXA in TBI showed a significant reduction in haemorrhage growth (OR=0.61, 95%CI 0.41 to 0.91) and mortality (OR=0.59, 95%CI 0.35 to 0.99) with TXA. Although the results from these trials are promising, the estimates are imprecise and there are no data on the effect of TXA on disability. Additionally, a nested study will be conducted in a subset of CRASH-3 trial participants. This nested study (CRASH-3 Intracranial Bleeding Sub-Study [CRASH-3 IBS]) will examine the effect of tranexamic acid on intracranial haemorrhage and cerebral ischaemia using CT Scans in approximately 1,000 patients randomised into the CRASH-3 trial.

AIM: The CRASH-3 trial will provide reliable evidence about the effect of tranexamic acid on mortality and disability in patients with TBI. The effect of TXA on the risk of vascular occlusive events and seizures will also be assessed.

PRIMARY OUTCOME: The primary outcome is death in hospital (within 28 days of injury) of patients randomised within 3 hours of injury (cause of death will be described).

SECONDARY OUTCOMES:

  1. Vascular occlusive events (myocardial infarction, stroke, pulmonary embolism, clinical evidence of deep vein thrombosis)
  2. In hospital disability assessed using the Disability Rating Scale and Patient Orientated Outcome
  3. Seizures
  4. Neurosurgical intervention
  5. Days in intensive care Other adverse events will be described

Other Outcome Measures: CRASH-3 IBS Primary outcome - the total volume of intracranial haemorrhage after randomisation, adjusting for baseline haemorrhage volume.

Secondary outcome -

  • Frequency of progressive haemorrhage: number of patients with a post-randomisation CT scan with total haemorrhage volume of more than 25% of the volume on the pre-randomisation scan;
  • Frequency of delayed haemorrhage: number of patients with haemorrhage on the post-randomisation CT scan when there was not one on the pre-randomisation scan;
  • New focal ischaemic lesions: ischaemic lesions which appear on the post-randomisation CT scan but not on the pre-randomisation scan;
  • Total volume of intracranial bleeding in patients who undergo surgical evacuation of haemorrhage after randomisation, adjusting for volume of baseline bleeding.

TRIAL DESIGN: A large, pragmatic, randomised, double blind, placebo controlled trial among 13,000 traumatic brain injury patients

DIAGNOSIS AND INCLUSION/EXCLUSION CRITERIA:

Adults with traumatic brain injury who

  • are within eight hours of injury
  • with any intracranial bleeding on CT scan or who have a GCS of 12 or less, and
  • have no significant extra-cranial haemorrhage The fundamental eligibility criterion is the responsible clinician's 'uncertainty' as to whether or not to use tranexamic acid in a particular patient with traumatic brain injury.

TEST PRODUCT, REFERENCE THERAPY, DOSE AND MODE OF ADMINISTRATION: A loading dose of tranexamic acid

(1 gram by intravenous injection) or placebo (sodium chloride 0.9%) will be given as soon as possible after randomisation. A maintenance dose of tranexamic acid (1 gram by intravenous injection) or placebo (sodium chloride 0.9%) will be given after the loading dose is finished.

SETTING: This trial will be coordinated from the London School of Hygiene & Tropical Medicine (University of London) and conducted worldwide in hospitals in low, middle and high income countries.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Traumatic Brain Injury
Intervention  ICMJE Drug: Tranexamic Acid
2 grams (1 gram over 10 minutes and 1 gram over 8 hours)
Study Arms  ICMJE
  • Experimental: Tranexamic acid
    Intervention: Drug: Tranexamic Acid
  • Placebo Comparator: Placebo
    (Sodium Chloride 0.9%)
    Intervention: Drug: Tranexamic Acid
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: September 14, 2016)
13000
Original Estimated Enrollment  ICMJE
 (submitted: July 25, 2011)
10000
Estimated Study Completion Date  ICMJE April 2020
Estimated Primary Completion Date September 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Adults with traumatic brain injury who

  • are within eight hours of injury (limited to within 3 hours from September, 2016)
  • with any intracranial bleeding on CT scan or who have a GCS of 12 or less, and
  • have no significant extra-cranial haemorrhage The fundamental eligibility criterion is the responsible clinician's 'uncertainty' as to whether or not to use tranexamic acid in a particular patient with traumatic brain injury

Exclusion Criteria:

The fundamental eligibility criterion is the responsible clinician's 'uncertainty' as to whether or not to use tranexamic acid in a particular patient with traumatic brain injury

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Georgia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01402882
Other Study ID Numbers  ICMJE ISRCTN15088122
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: After all relevant publications are completed, totally anonymised data will be available at https://ctu-app.lshtm.ac.uk/freebird/
Responsible Party London School of Hygiene and Tropical Medicine
Study Sponsor  ICMJE London School of Hygiene and Tropical Medicine
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Haleema Shakur LSHTM
PRS Account London School of Hygiene and Tropical Medicine
Verification Date March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP