EBQ:CRASH-2 Trial - Revision history

Kxl328: /* Criticisms & Further Discussion */

2019-04-21T18:12:36Z

Criticisms & Further Discussion

← Revisión anterior		Revisión del 18:12 21 abr 2019
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	*The fact that less blood was transfused in [[TXA]] administered groups raises questions regarding questions regarding the mechanism of action of antifibrinolysis as beneficial to mortality as well as the difficulty in parsing out survivor bias<ref>Kenji Inaba. Antifibrinolytics in Trauma Patients: Does It MATTER? Comment on “Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study” Arch Surg. 2012;147(2):119</ref>		*The fact that less blood was transfused in [[TXA]] administered groups raises questions regarding questions regarding the mechanism of action of antifibrinolysis as beneficial to mortality as well as the difficulty in parsing out survivor bias<ref>Kenji Inaba. Antifibrinolytics in Trauma Patients: Does It MATTER? Comment on “Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study” Arch Surg. 2012;147(2):119</ref>

	*The MATTERs study showed that rates of PE and [[DVT]]among patients who received [[TXA]] were, respectively, 9 and 12 times the rates among those who did not<ref>[[EBQ:MATTERs Study\|MATTERs Study]]</ref>		*The MATTERs study showed that rates of PE and [[DVT]] among patients who received [[TXA]] were, respectively, 9 and 12 times the rates among those who did not<ref>[[EBQ:MATTERs Study\|MATTERs Study]]</ref>

	==Funding==		==Funding==

Ostermayer: Text replacement - " DVT " to " DVT"

2017-01-27T16:30:04Z

Text replacement - " DVT " to " DVT"

← Revisión anterior		Revisión del 16:30 27 ene 2017
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	*The fact that less blood was transfused in [[TXA]] administered groups raises questions regarding questions regarding the mechanism of action of antifibrinolysis as beneficial to mortality as well as the difficulty in parsing out survivor bias<ref>Kenji Inaba. Antifibrinolytics in Trauma Patients: Does It MATTER? Comment on “Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study” Arch Surg. 2012;147(2):119</ref>		*The fact that less blood was transfused in [[TXA]] administered groups raises questions regarding questions regarding the mechanism of action of antifibrinolysis as beneficial to mortality as well as the difficulty in parsing out survivor bias<ref>Kenji Inaba. Antifibrinolytics in Trauma Patients: Does It MATTER? Comment on “Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study” Arch Surg. 2012;147(2):119</ref>

	*The MATTERs study showed that rates of PE and DVT among patients who received [[TXA]] were, respectively, 9 and 12 times the rates among those who did not<ref>[[EBQ:MATTERs Study\|MATTERs Study]]</ref>		*The MATTERs study showed that rates of PE and [[DVT]]among patients who received [[TXA]] were, respectively, 9 and 12 times the rates among those who did not<ref>[[EBQ:MATTERs Study\|MATTERs Study]]</ref>

	==Funding==		==Funding==

Neil.m.young at 16:56, 6 March 2016

2016-03-06T16:56:04Z

← Revisión anterior		Revisión del 16:56 6 mar 2016
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	[[EBQ:MATTERs Study\|MATTERs Study]]		[[EBQ:MATTERs Study\|MATTERs Study]]

	==~~Sources~~==		==References==
	<references/>		<references/>

Rossdonaldson1 at 15:41, 10 December 2014

2014-12-10T15:41:55Z

← Revisión anterior		Revisión del 15:41 10 dic 2014
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	==Clinical Question==		==Clinical Question==

	'''Does administration of tranexamic acid reduce the risk of death if administered early in severe trauma?'''		'''Does administration of [[tranexamic acid]] reduce the risk of death if administered early in severe trauma?'''

	==Conclusion==		==Conclusion==
	'''Tranexamic acid improves survival when administered in less than 3 hrs after injury in patients with significant hemorrhage.'''		'''[[Tranexamic acid]] improves survival when administered in less than 3 hrs after injury in patients with significant hemorrhage.'''

	==Major Points==		==Major Points==
	Tranexamic acid is a synthetic derivative of the aminoacid lysine that inhibits fibrinolysis by blocking the lysine binding sites on plasminogen.<ref> Okamoto S, Hijikata-Okunomiya A, Wanaka K, Okada Y,Okamoto U. Enzyme controlling medicines: introduction.		[[Tranexamic acid]] is a synthetic derivative of the aminoacid lysine that inhibits fibrinolysis by blocking the lysine binding sites on plasminogen.<ref> Okamoto S, Hijikata-Okunomiya A, Wanaka K, Okada Y,Okamoto U. Enzyme controlling medicines: introduction.
	Semin Thromb Hemost1997;23: 493–501</ref> Prior systemic review showed a third decrease in blood transfusions but no mortality benefit.<ref>Henry DA, Carless PA, Moxey AJ, et al. Anti-fi brinolytic use for minimising perioperative allogeneic blood transfusion.		Semin Thromb Hemost1997;23: 493–501</ref> Prior systemic review showed a third decrease in blood transfusions but no mortality benefit.<ref>Henry DA, Carless PA, Moxey AJ, et al. Anti-fi brinolytic use for minimising perioperative allogeneic blood transfusion.
	Cochrane Database Syst Rev 2007; 4: CD001886.</ref> In this study, however, the risk of death due to bleeding was significantly reduced (489 [4·9%] vs 574 [5·7%] as well as all-cause mortality (1463 [14.5%] tranexamic acid group vs 1613 [16.0%] placebo group).		Cochrane Database Syst Rev 2007; 4: CD001886.</ref> In this study, however, the risk of death due to bleeding was significantly reduced (489 [4·9%] vs 574 [5·7%] as well as all-cause mortality (1463 [14.5%] tranexamic acid group vs 1613 [16.0%] placebo group).
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	*Multicenter, randomized, placebo-controlled trial involving 274 hospitals in 40 countries		*Multicenter, randomized, placebo-controlled trial involving 274 hospitals in 40 countries
	*20,207 trauma patients with or at risk of significant hemorrhage		*20,207 trauma patients with or at risk of significant hemorrhage
	**Tranexamic acid (n=10,093)		**[[Tranexamic acid]] (n=10,093)
	**Placebo (n=10,114)		**Placebo (n=10,114)
	*Intention-to-treat analysis with 4 week followup		*Intention-to-treat analysis with 4 week followup
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	===Exclusion Criteria===		===Exclusion Criteria===
	#Clear contraindication to tranexamic acid		#Clear contraindication to [[tranexamic acid]]

	===Patient Characteristics===		===Patient Characteristics===
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	==Interventions==		==Interventions==
	#Loading dose of 1 g of tranexamic acid infused over 10 min, followed by an intravenous infusion of 1 g over 8 h, or placebo (0·9% saline).		#Loading dose of 1 g of [[tranexamic acid]] infused over 10 min, followed by an intravenous infusion of 1 g over 8 h, or placebo (0·9% saline).
	==Outcome==		==Outcome==

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	===Primary Outcomes===		===Primary Outcomes===
	*Primary outcome was death in hospital within 4 weeks of injury		*Primary outcome was death in hospital within 4 weeks of injury
	**TXA Group (n=10060) 1463 -- 14.5%		**[[TXA]] Group (n=10060) 1463 -- 14.5%
	**Placebo Group (n=1613) -- 16.0%		**Placebo Group (n=1613) -- 16.0%
	::RR (95%CI) 0.91 (0.85–0.97) pvalue - 0.0035		::RR (95%CI) 0.91 (0.85–0.97) pvalue - 0.0035
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	Vascular occlusive events (MI, CVA, PE, DVT)		Vascular occlusive events (MI, CVA, PE, DVT)
	:TXA: 1.7%		:[[TXA]]: 1.7%
	:Placebo: 2.0% (P=0.084)		:Placebo: 2.0% (P=0.084)

	Surgical intervention		Surgical intervention
	:TXA: 47.9%		:[[TXA]]: 47.9%
	:Placebo: 48.0% (P=0.79)		:Placebo: 48.0% (P=0.79)

	Blood transfusion		Blood transfusion
	:TXA: 50.4%		:[[TXA]]: 50.4%
	:Placebo: 51.3% (P=0.21)		:Placebo: 51.3% (P=0.21)

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	==Criticisms & Further Discussion==		==Criticisms & Further Discussion==
	*In 2012 the [[EBQ:MATTERs\|MATTERS Trial]] demonstrated the benefits of TXA in military trauma, particularly massive transfusion outcomes.<ref>[http://www.ncbi.nlm.nih.gov/pubmed/22006852 Morrison JJ, et al. "Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study." ''Arch Surg.'' 2012;147(2):113-9.]</ref>		*In 2012 the [[EBQ:MATTERs\|MATTERS Trial]] demonstrated the benefits of [[TXA]] in military trauma, particularly massive transfusion outcomes.<ref>[http://www.ncbi.nlm.nih.gov/pubmed/22006852 Morrison JJ, et al. "Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study." ''Arch Surg.'' 2012;147(2):113-9.]</ref>

	*Significant criticism exists regarding the randomization scheme where doctors could choose to randomize or not randomize based on treatment certainty. Also only approximately 5% of patients had bleeding as a cause of death and the was no data regarding the severity of hemorrhagic shock. There was also no decrease in blood transfusions and the majority of he population in the study had traumatic brain injury.<ref>Napolitano LM, Cohen MJ, Cotton BA, Schreiber MA, Moore EE. Tranexamic acid in trauma: how should we use it? JTrauma Acute Care Surg. 2013; 74:1575-1586.</ref>		*Significant criticism exists regarding the randomization scheme where doctors could choose to randomize or not randomize based on treatment certainty. Also only approximately 5% of patients had bleeding as a cause of death and the was no data regarding the severity of hemorrhagic shock. There was also no decrease in blood transfusions and the majority of he population in the study had traumatic brain injury.<ref>Napolitano LM, Cohen MJ, Cotton BA, Schreiber MA, Moore EE. Tranexamic acid in trauma: how should we use it? JTrauma Acute Care Surg. 2013; 74:1575-1586.</ref>

	*TXA was not included in any protocol associated with massive transfusion which is where the drug is often administered and most patients with acute traumatic coagulopathy were denied the drug in the study. <ref>Gruen RJ, Jacobs IG, Reade MC. Trauma and Tranexamic Acid. Med J Aus. 2013; 199:310-311. </ref>		*[[TXA]] was not included in any protocol associated with massive transfusion which is where the drug is often administered and most patients with acute traumatic coagulopathy were denied the drug in the study. <ref>Gruen RJ, Jacobs IG, Reade MC. Trauma and Tranexamic Acid. Med J Aus. 2013; 199:310-311. </ref>

	*Approximately half of the patients in the trial did not even require a transfusion.		*Approximately half of the patients in the trial did not even require a transfusion.

	*The fact that less blood was transfused in TXA administered groups raises questions regarding questions regarding the mechanism of action of antifibrinolysis as beneficial to mortality as well as the difficulty in parsing out survivor bias<ref>Kenji Inaba. Antifibrinolytics in Trauma Patients: Does It MATTER? Comment on “Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study” Arch Surg. 2012;147(2):119</ref>		*The fact that less blood was transfused in [[TXA]] administered groups raises questions regarding questions regarding the mechanism of action of antifibrinolysis as beneficial to mortality as well as the difficulty in parsing out survivor bias<ref>Kenji Inaba. Antifibrinolytics in Trauma Patients: Does It MATTER? Comment on “Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study” Arch Surg. 2012;147(2):119</ref>

	*The MATTERs study showed that rates of PE and DVT among patients who received ~~TxA~~ were, respectively, 9 and 12 times the rates among those who did not<ref>[[EBQ:MATTERs Study\|MATTERs Study]]</ref>		*The MATTERs study showed that rates of PE and DVT among patients who received [[TXA]] were, respectively, 9 and 12 times the rates among those who did not<ref>[[EBQ:MATTERs Study\|MATTERs Study]]</ref>

	==Funding==		==Funding==

Ostermayer: /* Funding */

2014-03-29T17:21:52Z

Funding

← Revisión anterior		Revisión del 17:21 29 mar 2014
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	==Funding==		==Funding==
	UK NIHR Health Technology Assessment programme, Pfizer, BUPA Foundation, and J P Moulton Charitable Foundation		UK NIHR Health Technology Assessment programme, Pfizer, BUPA Foundation, and J P Moulton Charitable Foundation

			==Further Reading==
			[[EBQ:MATTERs Study\|MATTERs Study]]

	==Sources==		==Sources==
	<references/>		<references/>

Ostermayer: /* Criticisms & Further Discussion */

2014-03-29T17:21:02Z

Criticisms & Further Discussion

← Revisión anterior		Revisión del 17:21 29 mar 2014
Línea 95:		Línea 95:
	*The fact that less blood was transfused in TXA administered groups raises questions regarding questions regarding the mechanism of action of antifibrinolysis as beneficial to mortality as well as the difficulty in parsing out survivor bias<ref>Kenji Inaba. Antifibrinolytics in Trauma Patients: Does It MATTER? Comment on “Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study” Arch Surg. 2012;147(2):119</ref>		*The fact that less blood was transfused in TXA administered groups raises questions regarding questions regarding the mechanism of action of antifibrinolysis as beneficial to mortality as well as the difficulty in parsing out survivor bias<ref>Kenji Inaba. Antifibrinolytics in Trauma Patients: Does It MATTER? Comment on “Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study” Arch Surg. 2012;147(2):119</ref>

	*The MATTERs study showed that rates of PE and DVT among patients who received TxA were, respectively, 9 and 12 times the rates among those who did not<ref>[[EBQ:MATTERs Study]]]</ref>		*The MATTERs study showed that rates of PE and DVT among patients who received TxA were, respectively, 9 and 12 times the rates among those who did not<ref>[[EBQ:MATTERs Study\|MATTERs Study]]</ref>

	==Funding==		==Funding==

Ostermayer: /* Criticisms & Further Discussion */

2014-03-29T17:20:34Z

Criticisms & Further Discussion

← Revisión anterior		Revisión del 17:20 29 mar 2014
Línea 95:		Línea 95:
	*The fact that less blood was transfused in TXA administered groups raises questions regarding questions regarding the mechanism of action of antifibrinolysis as beneficial to mortality as well as the difficulty in parsing out survivor bias<ref>Kenji Inaba. Antifibrinolytics in Trauma Patients: Does It MATTER? Comment on “Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study” Arch Surg. 2012;147(2):119</ref>		*The fact that less blood was transfused in TXA administered groups raises questions regarding questions regarding the mechanism of action of antifibrinolysis as beneficial to mortality as well as the difficulty in parsing out survivor bias<ref>Kenji Inaba. Antifibrinolytics in Trauma Patients: Does It MATTER? Comment on “Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study” Arch Surg. 2012;147(2):119</ref>

	*The MATTERs study showed that rates of PE and DVT among patients who received TxA were, respectively, 9 and 12 times the rates among those who did not<ref>[[EBQ:~~Matters~~ Study]]]</ref>		*The MATTERs study showed that rates of PE and DVT among patients who received TxA were, respectively, 9 and 12 times the rates among those who did not<ref>[[EBQ:MATTERs Study]]]</ref>

	==Funding==		==Funding==

Ostermayer at 17:20, 29 March 2014

2014-03-29T17:20:02Z

← Revisión anterior		Revisión del 17:20 29 mar 2014
Línea 95:		Línea 95:
	*The fact that less blood was transfused in TXA administered groups raises questions regarding questions regarding the mechanism of action of antifibrinolysis as beneficial to mortality as well as the difficulty in parsing out survivor bias<ref>Kenji Inaba. Antifibrinolytics in Trauma Patients: Does It MATTER? Comment on “Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study” Arch Surg. 2012;147(2):119</ref>		*The fact that less blood was transfused in TXA administered groups raises questions regarding questions regarding the mechanism of action of antifibrinolysis as beneficial to mortality as well as the difficulty in parsing out survivor bias<ref>Kenji Inaba. Antifibrinolytics in Trauma Patients: Does It MATTER? Comment on “Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study” Arch Surg. 2012;147(2):119</ref>

	*The MATTERs study showed that rates of PE and DVT among patients who received TxA were, respectively, 9 and 12 times the rates among those who did not<ref>[[EBQ:Matters]]]</ref>		*The MATTERs study showed that rates of PE and DVT among patients who received TxA were, respectively, 9 and 12 times the rates among those who did not<ref>[[EBQ:Matters Study]]]</ref>

	==Funding==		==Funding==

Ostermayer at 17:19, 29 March 2014

2014-03-29T17:19:09Z

← Revisión anterior		Revisión del 17:19 29 mar 2014
Línea 95:		Línea 95:
	*The fact that less blood was transfused in TXA administered groups raises questions regarding questions regarding the mechanism of action of antifibrinolysis as beneficial to mortality as well as the difficulty in parsing out survivor bias<ref>Kenji Inaba. Antifibrinolytics in Trauma Patients: Does It MATTER? Comment on “Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study” Arch Surg. 2012;147(2):119</ref>		*The fact that less blood was transfused in TXA administered groups raises questions regarding questions regarding the mechanism of action of antifibrinolysis as beneficial to mortality as well as the difficulty in parsing out survivor bias<ref>Kenji Inaba. Antifibrinolytics in Trauma Patients: Does It MATTER? Comment on “Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study” Arch Surg. 2012;147(2):119</ref>

	*The MATTERs study showed that rates of PE and DVT among patients who received TxA were, respectively, 9 and 12 times the rates among those who did not<ref>[[EBQ:Matters]]]		*The MATTERs study showed that rates of PE and DVT among patients who received TxA were, respectively, 9 and 12 times the rates among those who did not<ref>[[EBQ:Matters]]]</ref>

	==Funding==		==Funding==

Ostermayer at 17:18, 29 March 2014

2014-03-29T17:18:08Z

← Revisión anterior		Revisión del 17:18 29 mar 2014
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	*The MATTERs study showed that rates of PE and DVT among patients who received TxA were, respectively, 9 and 12 times the rates among those who did not<ref>[[EBQ:Matters]]]		*The MATTERs study showed that rates of PE and DVT among patients who received TxA were, respectively, 9 and 12 times the rates among those who did not<ref>[[EBQ:Matters]]]

			==Funding==
			UK NIHR Health Technology Assessment programme, Pfizer, BUPA Foundation, and J P Moulton Charitable Foundation

			==Sources==
			<references/>