Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage

NCT00375258 | Completed Phase 3 DMC

• 1 other identifier: ISRCTN86750102
• Study Type: interventional
• Target: 20,211
• Locations: 1 country
• Sites: 1

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).

Conditions

Hemorrhage

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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).

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

Secondary Outcomes (1)

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

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

Study Arms (2)

1

EXPERIMENTAL

Active

Drug: Tranexamic acid

2

PLACEBO COMPARATOR

Drug: Sodium Chloride 0.9%

Interventions

Tranexamic acid DRUG

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

1

Sodium Chloride 0.9% DRUG

Visual matched placebo

2

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead

Study Sites (1)

Over 50 countries Worldwide

London, United Kingdom

Location

Related Publications (12)

• 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.

  PMID: 15783255 BACKGROUND

• 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.

  PMID: 34022937 DERIVED

• 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.

  PMID: 32492040 DERIVED

• 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.

  PMID: 30642657 DERIVED

• 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.

  PMID: 28143564 DERIVED

• 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.

  PMID: 25498484 DERIVED

• 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.

  PMID: 24042386 DERIVED

• 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.

  PMID: 23477634 DERIVED

• 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.

  PMID: 21702233 DERIVED

• 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.

  PMID: 21559279 DERIVED

• 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.

  PMID: 21439633 DERIVED

• 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.

  PMID: 20554319 DERIVED

Related Links

• Trial website

MeSH Terms

Conditions

Hemorrhage

Interventions

Tranexamic Acid; Sodium Chloride

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Ian Roberts, MD

  London School of Hygiene and Tropical Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 11, 2006
• First Posted: September 12, 2006
• Study Start: May 1, 2005
• Primary Completion: February 1, 2010
• Study Completion: March 1, 2010
• Last Updated: June 30, 2011

Record last verified: 2011-06

Locations

GB (1)