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Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage

Primary Purpose

Hemorrhage

Status

Completed

Phase

Phase 3

Locations

United Kingdom

Study Type

Interventional

Intervention

Tranexamic acid

Sodium Chloride 0.9%

About this trial

This is an interventional treatment trial for Hemorrhage focused on measuring Adult trauma patients with ongoing significant haemorrhage or at risk of significant haemorrhage

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

All trauma patients with ongoing significant haemorrhage (systolic blood pressure less than 90 mmHg and/or heart rate more than 110 beats per minute), or who are considered to be at risk of significant haemorrhage, and are within 8 hours of the injury, are eligible for trial entry if they appear to be at least 16 years old. Although entry is allowed up to 8 hours from injury, the earlier that patients can be treated the better.

Exclusion Criteria:

The fundamental eligibility criterion is the responsible doctor's 'uncertainty' as to whether or not to use an antifibrinolytic agent in a particular adult with traumatic haemorrhage. Patients for whom the responsible doctor considers there is a clear indication for antifibrinolytic therapy should not be randomised. Likewise, patients for whom there is considered to be a clear contraindication to antifibrinolytic therapy (such as, perhaps, those who have clinical evidence of a thrombotic disseminated intravascular coagulation) should not be randomised. Where the responsible doctor is substantially uncertain as to whether or not to use an antifibrinolytic, all these patients are eligible for randomisation and should be considered for the trial. There are no other pre-specified exclusion criteria

Sites / Locations

Over 50 countries Worldwide

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm Description

Active

Outcomes

Primary Outcome Measures

Death in hospital within four weeks of injury (causes of death will be described to assess whether deaths were due to haemorrhage or vascular occlusion).

Secondary Outcome Measures

Receipt of a blood products transfusion, the number of units of blood products transfused, surgical intervention, and the occurrence of thrombo-embolic episodes

Full Information

NCT ID

NCT00375258

First Posted

September 11, 2006

Last Updated

June 29, 2011

Sponsor

London School of Hygiene and Tropical Medicine

1. Study Identification

Unique Protocol Identification Number

NCT00375258

Brief Title

Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage

Official Title

A Large Randomised Placebo Controlled Trial Among Trauma Patients With, or at Risk of, Significant Haemorrhage, of the Effects of Antifibrinolytic Treatment on Death and Transfusion Requirement

Study Type

Interventional

2. Study Status

Record Verification Date

June 2011

Overall Recruitment Status

Completed

Study Start Date

May 2005 (undefined)

Primary Completion Date

February 2010 (Actual)

Study Completion Date

March 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

London School of Hygiene and Tropical Medicine

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

CRASH 2 is a large pragmatic randomised placebo controlled trial of the effects of the early administration of the antifibrinolytic agent tranexamic acid on death, vascular events and transfusion requirements. Adults with trauma who are within 8 hours of injury and have either significant haemorrhage, or who are considered to be at risk of significant haemorrhage, are eligible if the responsible doctor is for any reason substantially uncertain whether or not to use an antifibrinolytic agent. Numbered drug or placebo packs will be available in each participating emergency department. Randomisation will involve calling a 24-hour freecall randomisation service. The call should last only a minute or two and at the end of it the randomisation service will specify which numbered treatment pack to use. For hospitals where telephone randomisation is not feasible, randomisation will be by taking the next consecutively numbered treatment pack. No extra tests are required but a short form must be completed one month later or on discharge or on death (whichever occurs first).

Detailed Description

See trial website for full protocol. This is an international trial with over 300 hospitals in about 40 countries worldwide.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hemorrhage

Keywords

Adult trauma patients with ongoing significant haemorrhage or at risk of significant haemorrhage

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

20211 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

Active

Arm Title

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

Tranexamic acid

Intervention Description

Loading dose of 1 gram then 1 gram by infusion over 8 hours

Intervention Type

Drug

Intervention Name(s)

Sodium Chloride 0.9%

Intervention Description

Visual matched placebo

Primary Outcome Measure Information:

Title

Death in hospital within four weeks of injury (causes of death will be described to assess whether deaths were due to haemorrhage or vascular occlusion).

Time Frame

Death, discharge or four weeks post randomisation whichever occurs first.

Secondary Outcome Measure Information:

Title

Receipt of a blood products transfusion, the number of units of blood products transfused, surgical intervention, and the occurrence of thrombo-embolic episodes

Time Frame

Death, discharge or four weeks post randomisation whichever occurs first.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

16 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: All trauma patients with ongoing significant haemorrhage (systolic blood pressure less than 90 mmHg and/or heart rate more than 110 beats per minute), or who are considered to be at risk of significant haemorrhage, and are within 8 hours of the injury, are eligible for trial entry if they appear to be at least 16 years old. Although entry is allowed up to 8 hours from injury, the earlier that patients can be treated the better. Exclusion Criteria: The fundamental eligibility criterion is the responsible doctor's 'uncertainty' as to whether or not to use an antifibrinolytic agent in a particular adult with traumatic haemorrhage. Patients for whom the responsible doctor considers there is a clear indication for antifibrinolytic therapy should not be randomised. Likewise, patients for whom there is considered to be a clear contraindication to antifibrinolytic therapy (such as, perhaps, those who have clinical evidence of a thrombotic disseminated intravascular coagulation) should not be randomised. Where the responsible doctor is substantially uncertain as to whether or not to use an antifibrinolytic, all these patients are eligible for randomisation and should be considered for the trial. There are no other pre-specified exclusion criteria

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ian Roberts, MD

Organizational Affiliation

London School of Hygiene and Tropical Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Over 50 countries Worldwide

City

London

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

15783255

Citation

Coats T, Hunt B, Roberts I, Shakur H. Antifibrinolytic agents in traumatic haemorrhage. PLoS Med. 2005 Mar;2(3):e64. doi: 10.1371/journal.pmed.0020064. Epub 2005 Mar 29.

Results Reference

background

PubMed Identifier

34022937

Citation

Edgar K, Roberts I, Sharples L. Including random centre effects in design, analysis and presentation of multi-centre trials. Trials. 2021 May 22;22(1):357. doi: 10.1186/s13063-021-05266-w.

Results Reference

derived

PubMed Identifier

32492040

Citation

Kolin DA, Shakur-Still H, Bello A, Chaudhri R, Bates I, Roberts I. Risk factors for blood transfusion in traumatic and postpartum hemorrhage patients: Analysis of the CRASH-2 and WOMAN trials. PLoS One. 2020 Jun 3;15(6):e0233274. doi: 10.1371/journal.pone.0233274. eCollection 2020.

Results Reference

derived

PubMed Identifier

30642657

Citation

Nishijima DK, Kuppermann N, Roberts I, VanBuren JM, Tancredi DJ. The Effect of Tranexamic Acid on Functional Outcomes: An Exploratory Analysis of the CRASH-2 Randomized Controlled Trial. Ann Emerg Med. 2019 Jul;74(1):79-87. doi: 10.1016/j.annemergmed.2018.11.018. Epub 2019 Jan 12.

Results Reference

derived

PubMed Identifier

28143564

Citation

Roberts I, Edwards P, Prieto D, Joshi M, Mahmood A, Ker K, Shakur H. Tranexamic acid in bleeding trauma patients: an exploration of benefits and harms. Trials. 2017 Jan 31;18(1):48. doi: 10.1186/s13063-016-1750-1.

Results Reference

derived

PubMed Identifier

25498484

Citation

Roberts I, Prieto-Merino D, Manno D. Mechanism of action of tranexamic acid in bleeding trauma patients: an exploratory analysis of data from the CRASH-2 trial. Crit Care. 2014 Dec 13;18(6):685. doi: 10.1186/s13054-014-0685-8.

Results Reference

derived

PubMed Identifier

24042386

Citation

Meurer WJ. Tranexamic acid reduced mortality in trauma patients who were bleeding or at risk for bleeding. Ann Intern Med. 2013 Sep 17;159(6):JC3. doi: 10.7326/0003-4819-159-6-201309170-02003. No abstract available.

Results Reference

derived

PubMed Identifier

23477634

Citation

Roberts I, Shakur H, Coats T, Hunt B, Balogun E, Barnetson L, Cook L, Kawahara T, Perel P, Prieto-Merino D, Ramos M, Cairns J, Guerriero C. 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. Health Technol Assess. 2013 Mar;17(10):1-79. doi: 10.3310/hta17100.

Results Reference

derived

PubMed Identifier

21702233

Citation

Williams-Johnson JA, McDonald AH, Strachan GG, Williams EW. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2) A randomised, placebo-controlled trial. West Indian Med J. 2010 Dec;59(6):612-24.

Results Reference

derived

PubMed Identifier

21559279

Citation

Guerriero C, Cairns J, Perel P, Shakur H, Roberts I; CRASH 2 trial collaborators. Cost-effectiveness analysis of administering tranexamic acid to bleeding trauma patients using evidence from the CRASH-2 trial. PLoS One. 2011 May 3;6(5):e18987. doi: 10.1371/journal.pone.0018987.

Results Reference

derived

PubMed Identifier

21439633

Citation

CRASH-2 collaborators; Roberts I, Shakur H, Afolabi A, Brohi K, Coats T, Dewan Y, Gando S, Guyatt G, Hunt BJ, Morales C, Perel P, Prieto-Merino D, Woolley T. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet. 2011 Mar 26;377(9771):1096-101, 1101.e1-2. doi: 10.1016/S0140-6736(11)60278-X.

Results Reference

derived

PubMed Identifier

20554319

Citation

CRASH-2 trial collaborators; Shakur H, Roberts I, Bautista R, Caballero J, Coats T, Dewan Y, El-Sayed H, Gogichaishvili T, Gupta S, Herrera J, Hunt B, Iribhogbe P, Izurieta M, Khamis H, Komolafe E, Marrero MA, Mejia-Mantilla J, Miranda J, Morales C, Olaomi O, Olldashi F, Perel P, Peto R, Ramana PV, Ravi RR, Yutthakasemsunt S. Effects 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 Jul 3;376(9734):23-32. doi: 10.1016/S0140-6736(10)60835-5. Epub 2010 Jun 14.

Results Reference

derived

Links:

URL

http://www.crash2.lshtm.ac.uk

Description

Trial website

Learn more about this trial

Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage

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