EBQ:Halt It Trial - Revision history

Danbot: Mark as Complete - article has all required sections

2026-03-21T22:10:42Z

Mark as Complete - article has all required sections

← Older revision		Revision as of 22:10, 21 March 2026
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	\| fulltexturl= https://doi.org/10.1016/S0140-6736(20)30848-5		\| fulltexturl= https://doi.org/10.1016/S0140-6736(20)30848-5
	\| pdfurl= https://www.thelancet.com/action/showPdf?pii=S0140-6736%2820%2930848-5		\| pdfurl= https://www.thelancet.com/action/showPdf?pii=S0140-6736%2820%2930848-5
			\| status = Complete
	}}		}}
	==Clinical Question==		==Clinical Question==

Rossdonaldson1: Rossdonaldson1 moved page Halt it to EBQ:Halt It Trial

2020-07-18T12:54:17Z

Rossdonaldson1 moved page Halt it to EBQ:Halt It Trial

← Older revision	Revision as of 12:54, 18 July 2020
(No difference)

Rossdonaldson1: /* Major Points */

2020-07-18T12:52:44Z

Major Points

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	==Major Points==		==Major Points==
	Tranexamic acid (TXA) is a synthetic lysine derivative that decreases fibrinolysis by inhibiting the conversion of plasminogen to plasmin. It has been used broadly in trauma patients with hemodynamically significant bleeding and appears to confer a mortality benefit in this population<ref>Roberts I et al. Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial. The Lancet. 2020; 395(10241):1927-1936</ref>. A prior systematic review of TXA for use in acute gastrointestinal bleeding suggested a mortality benefit, although the review was based on a series of small studies prone to bias<ref>Bennett C, Klingenberg SL, Langholz E, Gluud LL. Tranexamic acid for upper gastrointestinal bleeding. The Cochrane database of systematic reviews. 2014</ref>.		[[Tranexamic acid]] (TXA) is a synthetic lysine derivative that decreases fibrinolysis by inhibiting the conversion of plasminogen to plasmin. It has been used broadly in trauma patients with hemodynamically significant bleeding and appears to confer a mortality benefit in this population<ref>Roberts I et al. Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial. The Lancet. 2020; 395(10241):1927-1936</ref>. A prior systematic review of TXA for use in acute gastrointestinal bleeding suggested a mortality benefit, although the review was based on a series of small studies prone to bias<ref>Bennett C, Klingenberg SL, Langholz E, Gluud LL. Tranexamic acid for upper gastrointestinal bleeding. The Cochrane database of systematic reviews. 2014</ref>.

	HALT-IT is the first large, pragmatic, international, double-blind RCT to systematically evaluate the use of TXA in acute undifferentiated GI bleed. In this study, patients that received TXA 1g IV loading dose followed by a 3g infusion over 24 hours had the same mortality rate from bleeding at five days as patients receiving a matching normal saline placebo (222 [3.7%] intervention group vs 226 [3.8%] placebo, RR 0.99). All-cause mortality at 28 days was also no different between groups. There was a suggestion of increased venous thromboembolic events in the TXA group (48 [0.8%] vs 26 [0.4%], RR 1.85 [CI 1.15-2.98]).		HALT-IT is the first large, pragmatic, international, double-blind RCT to systematically evaluate the use of TXA in acute undifferentiated GI bleed. In this study, patients that received TXA 1g IV loading dose followed by a 3g infusion over 24 hours had the same mortality rate from bleeding at five days as patients receiving a matching normal saline placebo (222 [3.7%] intervention group vs 226 [3.8%] placebo, RR 0.99). All-cause mortality at 28 days was also no different between groups. There was a suggestion of increased venous thromboembolic events in the TXA group (48 [0.8%] vs 26 [0.4%], RR 1.85 [CI 1.15-2.98]).

Rossdonaldson1: /* See Also */

2020-07-18T12:52:29Z

Nate488: /* See Also */

2020-07-17T20:22:24Z

Nate488: A large, double-blind RCT showed no benefit for using tranexamic acid for adults with acute gastrointestinal bleeding, and suggested there may be increased harm from DVT/PE.

2020-07-10T19:55:39Z

A large, double-blind RCT showed no benefit for using tranexamic acid for adults with acute gastrointestinal bleeding, and suggested there may be increased harm from DVT/PE.

New page

{{JC info
| title= Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial
| expansion=
| published= Jun 20, 2020
| author= Roberts I, Shakur-Still H, Afolabi A, et al.
| journal= Lancet
| year= 2020
| volume= 395
| issue= 10241
| pages= 1927-1936
| pmid= 32563378
| fulltexturl= https://doi.org/10.1016/S0140-6736(20)30848-5
| pdfurl= https://www.thelancet.com/action/showPdf?pii=S0140-6736%2820%2930848-5
}}
==Clinical Question==
Does high-dose IV tranexamic acid reduce death due to bleeding within five days in adult patients with acute gastrointestinal bleeding compared to placebo?

==Conclusion==
Tranexamic acid confers no benefit on 5-day mortality due to bleeding in adult patients with acute GI bleed.

==Major Points==
Tranexamic acid (TXA) is a synthetic lysine derivative that decreases fibrinolysis by inhibiting the conversion of plasminogen to plasmin. It has been used broadly in trauma patients with hemodynamically significant bleeding and appears to confer a mortality benefit in this population<ref>Roberts I et al. Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial. The Lancet. 2020; 395(10241):1927-1936</ref>. A prior systematic review of TXA for use in acute gastrointestinal bleeding suggested a mortality benefit, although the review was based on a series of small studies prone to bias<ref>Bennett C, Klingenberg SL, Langholz E, Gluud LL. Tranexamic acid for upper gastrointestinal bleeding. The Cochrane database of systematic reviews. 2014</ref>.

HALT-IT is the first large, pragmatic, international, double-blind RCT to systematically evaluate the use of TXA in acute undifferentiated GI bleed. In this study, patients that received TXA 1g IV loading dose followed by a 3g infusion over 24 hours had the same mortality rate from bleeding at five days as patients receiving a matching normal saline placebo (222 [3.7%] intervention group vs 226 [3.8%] placebo, RR 0.99). All-cause mortality at 28 days was also no different between groups. There was a suggestion of increased venous thromboembolic events in the TXA group (48 [0.8%] vs 26 [0.4%], RR 1.85 [CI 1.15-2.98]).

==Study Design==
Large, pragmatic, multicenter international placebo-controlled RCT, conducted at 164 hospitals in 15 countries
*12,009 patients enrolled with acute GI bleeding
**[[Tranexamic_acid|Tranexamic acid]] (n=5,994)
***Placebo (n=6,015)

==Population==
===Patient Demographics===
*Patients older (mean age 58), male (65%), and mostly upper GI bleeds (90%)
*Mean time to randomization from onset of bleeding 22h
*Most patients (57%) did not display signs of shock on initial presentation
===Inclusion Criteria===
*Adult patients with acute gastrointestinal bleeding
*Clinician defined bleeding as significant, meaning possibility of death from bleeding
**Age of inclusion either 16 or 18 depending on definition of "adult" in home country
*Clinician had to be "uncertain" whether or not to use TXA
===Exclusion Criteria===
*Clinician-determined clear indication for TXA
*Clinician-determined clear contraindication for TXA
==Interventions==
*TXA 1g IV over 10 minloading dose followed by a 3g infusion in NS over 24 hours
==Outcomes==

===Primary Outcome===
*Death from bleeding at 5 days
**No difference between TXA (222, 3.7%)and placebo (226, 3.8%)
===Secondary Outcomes===
*All-cause mortality at 28 days
**Originally was the primary outcome, replaced by the above (see discussion)
**No difference between TXA (9.5%) and placebo (9.2%), RR 1·03, 95% CI 0·92– 1.16
*No difference in rebleeding, need for endoscopy/surgery, transfusion requirement, or mortality from other subgroups (i.e. infection, organ failure, etc)
*Thromboembolic events
**Any: 1.4% in TXA group vs 1.2% in placebo (RR 1.20, 95% CI 0.88-1.64)
**Venous (DVT and PE): 0.8% in TXA group vs 0.4% in placebo (RR 1.85, 95% CI 1.15-2.98)
*Seizures
**0.6% in TXA group vs 0.4% in placebo (RR 1.73, 95% CI 1.03-2.93

===Subgroup analysis===
4 preplanned subgroups within the primary outcome:
*Time from onset of bleeding, greater or less than 3h
*Site of bleed, upper or lower
*Varices and comorbid liver disease vs other causes of bleeding
*Rockall score

TXA showed no benefit in any subgroup.

==Criticisms & Further Discussion==
*Previous positive studies of TXA on GI bleeds have been small or observational and subject to bias
*This large RCT is well-designed, pragmatic, and answers a clinically relevant question
*The study authors changed the original primary outcome from all-cause 28-day mortality to death due to bleeding at 5 days
**During an interim analysis authors noted that >50% of deaths were from non-hemorrhagic causes
**New primary outcome is disease-specific and at the judgment of the clinician
*Patients for whom TXA was thought to be "clearly indicated" were excluded from the trial
**Some sicker patients who could have benefited from TXA may have been excluded
*Time to randomization was long (22 hours on average); CRASH-2 signaled that earlier administration of TXA is better
**However, GI bleed patients tend to present roughly in the timeframe represented in the trial

==External Links==

==See Also==
[[EBQ:CRASH-2_Trial|CRASH-2 Trial]]
[[Tranexamic_acid|Tranexamic Acid]]
[[EBQ:MATTERs_Study|MATTERs Study]]
==Funding==
The UK National Institute for Health Research Health Technology Assessment Programme
==References==
<references/>

[[Category:EBQ]]

← Older revision		Revision as of 12:52, 18 July 2020
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	==See Also==		==See Also==
	[[EBQ:CRASH-2_Trial\|CRASH-2 Trial]]		*[[EBQ:CRASH-2_Trial\|CRASH-2 Trial]]
			*[[Tranexamic acid]]
	[[~~Tranexamic_acid\|~~Tranexamic ~~Acid~~]]		*[[EBQ:MATTERs_Study\|MATTERs Study]]

	[[EBQ:MATTERs_Study\|MATTERs Study]]

	==Funding==		==Funding==

← Older revision		Revision as of 20:22, 17 July 2020
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	==See Also==		==See Also==
	[[EBQ:CRASH-2_Trial\|CRASH-2 Trial]]		[[EBQ:CRASH-2_Trial\|CRASH-2 Trial]]

	[[Tranexamic_acid\|Tranexamic Acid]]		[[Tranexamic_acid\|Tranexamic Acid]]

	[[EBQ:MATTERs_Study\|MATTERs Study]]		[[EBQ:MATTERs_Study\|MATTERs Study]]

	==Funding==		==Funding==
	The UK National Institute for Health Research Health Technology Assessment Programme		The UK National Institute for Health Research Health Technology Assessment Programme