ClinicalTrials.gov

History of Changes for Study: NCT01658124
Haemorrhage Alleviation With Tranexamic Acid- Intestinal System (HALT-IT)
Latest version (submitted April 16, 2020) on ClinicalTrials.gov
  • A study version is represented by a row in the table.
  • Select two study versions to compare. One each from columns A and B.
  • Choose either the "Merged" or "Side-by-Side" comparison format to specify how the two study versions are to be displayed. The Side-by-Side format only applies to the Protocol section of the study.
  • Click "Compare" to do the comparison and show the differences.
  • Select a version's Submitted Date link to see a rendering of the study for that version.
  • The yellow A/B choices in the table indicate the study versions currently compared below. A yellow table row indicates the study version currently being viewed.
  • Hover over the "Recruitment Status" to see how the study's recruitment status changed.
  • Study edits or deletions are displayed in red.
  • Study additions are displayed in green.
Study Record Versions
Version A B Submitted Date Changes
1 August 1, 2012 None (earliest Version on record)
2 December 19, 2013 Recruitment Status, Study Status, Contacts/Locations and Oversight
3 January 7, 2015 Arms and Interventions and Study Status
4 September 7, 2015 Study Status
5 September 8, 2016 Study Status
6 December 19, 2016 Study Status
7 November 29, 2017 Study Status, Outcome Measures, References and Study Design
8 December 10, 2018 Study Status
9 May 24, 2019 Outcome Measures, Study Status, Contacts/Locations and Study Description
10 June 19, 2019 Sponsor/Collaborators and Study Status
11 April 8, 2020 Recruitment Status, Study Status and Contacts/Locations
12 April 16, 2020 Recruitment Status, Study Status and Study Design
Comparison Format:

Scroll up to access the controls

Changes (Side-by-Side) for Study: NCT01658124
August 1, 2012 (v1) -- November 29, 2017 (v7)

Changes in: Study Status, Outcome Measures, Contacts/Locations, References, Arms and Interventions, Study Design and Oversight

Study Identification
Unique Protocol ID: ISRCTN11225767 ISRCTN11225767
Brief Title: Haemorrhage Alleviation With Tranexamic Acid- Intestinal System (HALT-IT)Haemorrhage Alleviation With Tranexamic Acid- Intestinal System (HALT-IT)
Official Title: Tranexamic Acid for the Treatment of Gastrointestinal Haemorrhage: an International Randomised, Double Blind Placebo Controlled Trial Tranexamic Acid for the Treatment of Gastrointestinal Haemorrhage: an International Randomised, Double Blind Placebo Controlled Trial
Secondary IDs:
Study Status
Record Verification: August 2012 December 2016
Overall Status: Not yet recruiting Recruiting
Study Start: January 2013 January 2013
Primary Completion: October 2016 [Anticipated ] June 2019 [Anticipated ]
Study Completion: October 2017 [Anticipated ] September 2020 [Anticipated ]
First Submitted: July 26, 2012 July 26, 2012
First Submitted that
Met QC Criteria:
August 1, 2012 August 1, 2012
First Posted: August 6, 2012 [Estimate ] August 6, 2012 [Estimate ]
Last Update Submitted that
Met QC Criteria:
August 1, 2012 November 29, 2017
Last Update Posted: August 6, 2012 [Estimate ] December 2, 2017 [Actual ]
Sponsor/Collaborators
Sponsor: London School of Hygiene and Tropical Medicine London School of Hygiene and Tropical Medicine
Responsible Party: Sponsor Sponsor
Collaborators: Global trial which will include about 40 countries and over 200 hospitals Global trial which will include about 40 countries and over 200 hospitals
Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: Yes Yes
Study Description
Brief Summary: Severe bleeding in the digestive system is a common symptom of many diseases. Each year, about 50,000 people end up in British hospitals because of this problem and about 5,000 of them die. The most common cause of this bleeding is stomach ulcers. In sub-Saharan Africa, schistosomiasis (parasitic worms) is responsible for about 130,000 deaths from stomach bleeding each year. From previous research in other bleeding conditions such as surgery and trauma, we know that a drug called tranexamic acid can reduce bleeding and save lives. We now want to do the HALT-IT trial to see if giving tranexamic acid can save lives and if there are any complications in people with severe bleeding from the digestive system. Severe bleeding in the digestive system is a common symptom of many diseases. Each year, about 50,000 people end up in British hospitals because of this problem and about 5,000 of them die. The most common cause of this bleeding is stomach ulcers. In sub-Saharan Africa, schistosomiasis (parasitic worms) is responsible for about 130,000 deaths from stomach bleeding each year. From previous research in other bleeding conditions such as surgery and trauma, we know that a drug called tranexamic acid can reduce bleeding and save lives. We now want to do the HALT-IT trial to see if giving tranexamic acid can save lives and if there are any complications in people with severe bleeding from the digestive system.
Detailed Description:

BACKGROUND: Acute gastrointestinal (GI) haemorrhage is one of the most common gastrointestinal emergencies. It is an important cause of mortality and morbidity in high, middle and low income countries. The most common causes of upper GI haemorrhage are peptic ulcer, oesophageal varices and erosive mucosal disease, although the relative frequency of the different causes varies in different countries. Acute upper GI haemorrhage accounts for around 50,000 hospital admissions each year in the UK and has a case fatality of about 10%. The incidence is highest among the most disadvantaged social groups. Lower GI haemorrhage accounts for a further 15,000 hospital admissions each year and has a case fatality of between 10% and 20%. Upper GI haemorrhage is also a common medical emergency in low and middle income countries. Patients are usually young and poor and the source of bleeding is more often oesophageal varices. Fibrinolysis may play an important pathological role in GI haemorrhage due to premature breakdown of haemostatic plugs at sites of mucosal injury. Tranexamic acid (TXA) is a synthetic derivative of the amino acid lysine which inhibits fibrinolysis by blocking the lysine binding sites on plasminogen. It is a widely used treatment with a known safety profile. There is reliable evidence that TXA reduces blood transfusion in surgical patients. A systematic review including 65 trials shows that TXA reduces the probability of blood transfusion by 39% (RR=0.61, 95% CI 0.53 to 0.70) compared to control. The effect of TXA on the risk of thromboembolic events in surgical patients remains uncertain, although there is no evidence of any increase in risk. The CRASH-2 trial showed that administration of TXA significantly reduces deaths due to bleeding (RR=0.85, 95% CI 0.76 to 0.96), and all-cause mortality (RR=0.91, 95% CI 0.85 to 0.97) in trauma patients with significant extra-cranial bleeding, with no increase in vascular occlusive events. A systematic review conducted by the investigators of TXA in GI bleeding identified nine randomised trials including a total of 1721 patients. Although there was a statistically significant reduction in the risk of death in patients treated with TXA (RR=0.66, 95% CI 0.47 to 0.93), the estimate is imprecise and the overall quality of trials was poor. Furthermore, all but three of the trials were conducted before the widespread use of therapeutic endoscopy and proton pump inhibitors and even in aggregate the trials were too small to assess the effects of TXA on other clinical important outcomes such as thromboembolic events. For these reasons, the effectiveness and safety of TXA for GI haemorrhage is uncertain and there are currently no formal recommendations for its use as a treatment for GI bleeding.

AIM: The HALT-IT trial will determine the effect of TXA on mortality, morbidity (re-bleeding, non-fatal vascular events), blood transfusion, surgical intervention and health status in patients with acute gastrointestinal haemorrhage.

PRIMARY OUTCOME: The primary outcome is death in hospital within 28 days of randomisation (cause-specific mortality will also be recorded).

SECONDARY OUTCOMES:

  1. Re-bleeding
  2. Need for salvage surgery or radiological intervention
  3. Blood transfusion - blood or blood component units transfused
  4. Thromboembolic events (myocardial infarction, stroke, pulmonary embolism, deep vein thrombosis)
  5. Other adverse medical events (including renal failure, significant cardiac event, respiratory failure, hepatic failure, sepsis, pneumonia, seizure)
  6. Functional status measured using the Katz Index of Independence in Activities of Daily Living
  7. Time spent at an intensive care unit
  8. Length of stay in hospital
  9. Patient status (death, hospital readmission) at 12 months will be ascertained if appropriate databases are available in the recruiting country

TRIAL DESIGN:

A pragmatic, randomised, double blind, placebo controlled trial among 8,000 patients with clinically significant gastrointestinal bleeding

DIAGNOSIS AND INCLUSION/EXCLUSION CRITERIA:

Adults with acute significant upper or lower gastrointestinal bleeding. The diagnosis of significant bleeding is clinical but may include patients with hypotension, tachycardia, or those likely to need transfusion, urgent endoscopy or surgery. The fundamental eligibility criterion is the responsible clinician's 'uncertainty' as to whether or not to use tranexamic acid in a particular patient with gastrointestinal bleeding. If the clinician believes there is a clear indication for, or clear contraindication to, tranexamic acid use, the particular patient should not be randomised. There are no other pre-specified exclusion criteria.

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 followed by an intravenous infusion of 3 grams over 24 hours or placebo (sodium chloride 0.9%).

SETTING:

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

DURATION OF TREATMENT AND PARTICIPATION:

The first dose will be given immediately after randomisation and the maintenance dose will be given immediately after the loading dose over 24 hours. Participation will end at discharge from randomising hospital, death or at 28 days post randomisation whichever occurs first.

CRITERIA FOR EVALUATION:

All patients randomly assigned to one of the treatments will be analysed together (regardless of whether or not they completed or received that treatment) on an intention to treat basis.

BACKGROUND: Acute gastrointestinal (GI) haemorrhage is one of the most common gastrointestinal emergencies. It is an important cause of mortality and morbidity in high, middle and low income countries. The most common causes of upper GI haemorrhage are peptic ulcer, oesophageal varices and erosive mucosal disease, although the relative frequency of the different causes varies in different countries. Acute upper GI haemorrhage accounts for around 50,000 hospital admissions each year in the UK and has a case fatality of about 10%. The incidence is highest among the most disadvantaged social groups. Lower GI haemorrhage accounts for a further 15,000 hospital admissions each year and has a case fatality of between 10% and 20%. Upper GI haemorrhage is also a common medical emergency in low and middle income countries. Patients are usually young and poor and the source of bleeding is more often oesophageal varices. Fibrinolysis may play an important pathological role in GI haemorrhage due to premature breakdown of haemostatic plugs at sites of mucosal injury. Tranexamic acid (TXA) is a synthetic derivative of the amino acid lysine which inhibits fibrinolysis by blocking the lysine binding sites on plasminogen. It is a widely used treatment with a known safety profile. There is reliable evidence that TXA reduces blood transfusion in surgical patients. A systematic review including 65 trials shows that TXA reduces the probability of blood transfusion by 39% (RR=0.61, 95% CI 0.53 to 0.70) compared to control. The effect of TXA on the risk of thromboembolic events in surgical patients remains uncertain, although there is no evidence of any increase in risk. The CRASH-2 trial showed that administration of TXA significantly reduces deaths due to bleeding (RR=0.85, 95% CI 0.76 to 0.96), and all-cause mortality (RR=0.91, 95% CI 0.85 to 0.97) in trauma patients with significant extra-cranial bleeding, with no increase in vascular occlusive events. A systematic review conducted by the investigators of TXA in GI bleeding identified nine randomised trials including a total of 1721 patients. Although there was a statistically significant reduction in the risk of death in patients treated with TXA (RR=0.66, 95% CI 0.47 to 0.93), the estimate is imprecise and the overall quality of trials was poor. Furthermore, all but three of the trials were conducted before the widespread use of therapeutic endoscopy and proton pump inhibitors and even in aggregate the trials were too small to assess the effects of TXA on other clinical important outcomes such as thromboembolic events. For these reasons, the effectiveness and safety of TXA for GI haemorrhage is uncertain and there are currently no formal recommendations for its use as a treatment for GI bleeding.

AIM: The HALT-IT trial will determine the effect of TXA on mortality, morbidity (re-bleeding, non-fatal vascular events), blood transfusion, surgical intervention and health status in patients with acute gastrointestinal haemorrhage.

PRIMARY OUTCOME: The primary outcome is death in hospital within 28 days of randomisation (cause-specific mortality will also be recorded).

SECONDARY OUTCOMES:

  1. Re-bleeding
  2. Need for salvage surgery or radiological intervention
  3. Blood transfusion - blood or blood component units transfused
  4. Thromboembolic events (myocardial infarction, stroke, pulmonary embolism, deep vein thrombosis)
  5. Other adverse medical events (including renal failure, significant cardiac event, respiratory failure, hepatic failure, sepsis, pneumonia, seizure)
  6. Functional status measured using the Katz Index of Independence in Activities of Daily Living
  7. Time spent at an intensive care unit
  8. Length of stay in hospital
  9. Patient status (death, hospital readmission) at 12 months will be ascertained if appropriate databases are available in the recruiting country

TRIAL DESIGN:

A pragmatic, randomised, double blind, placebo controlled trial among 8,000 patients with clinically significant gastrointestinal bleeding

DIAGNOSIS AND INCLUSION/EXCLUSION CRITERIA:

Adults with acute significant upper or lower gastrointestinal bleeding. The diagnosis of significant bleeding is clinical but may include patients with hypotension, tachycardia, or those likely to need transfusion, urgent endoscopy or surgery. The fundamental eligibility criterion is the responsible clinician's 'uncertainty' as to whether or not to use tranexamic acid in a particular patient with gastrointestinal bleeding. If the clinician believes there is a clear indication for, or clear contraindication to, tranexamic acid use, the particular patient should not be randomised. There are no other pre-specified exclusion criteria.

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 followed by an intravenous infusion of 3 grams over 24 hours or placebo (sodium chloride 0.9%).

SETTING:

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

DURATION OF TREATMENT AND PARTICIPATION:

The first dose will be given immediately after randomisation and the maintenance dose will be given immediately after the loading dose over 24 hours. Participation will end at discharge from randomising hospital, death or at 28 days post randomisation whichever occurs first.

CRITERIA FOR EVALUATION:

All patients randomly assigned to one of the treatments will be analysed together (regardless of whether or not they completed or received that treatment) on an intention to treat basis.

Conditions
Conditions: Gastrointestinal Bleeding Gastrointestinal Bleeding
Keywords: haemorrhage,antifibrinolytic, clinical trial, haemorrhage,antifibrinolytic, clinical trial,
Study Design
Study Type: InterventionalInterventional
Primary Purpose: TreatmentTreatment
Study Phase: Phase 3Phase 3
Interventional Study Model: Parallel Assignment Parallel Assignment
Number of Arms: 22
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation: RandomizedRandomized
Enrollment: 8000 [Anticipated ] 12000 [Anticipated ]
Arms and Interventions
Arms Assigned Interventions
Experimental: Tranexamic acid
(total dose 2 8 grams)
Drug: Tranexamic Acid
Placebo Comparator: Placebo
(Sodium Chloride 0.9%)
Drug: Placebo
Outcome Measures
Primary Outcome Measures:
1. The primary outcome is death in hospital (cause-specific mortality will also be recorded)
within 28 days of randomisation
The primary outcome is death in hospital (cause-specific mortality will also be recorded - haemorrhage, myocardial infarction, stroke, pulmonary embolism, pneumonia, malignancy, other)
within 28 days of randomisation
Secondary Outcome Measures:
2. Re-bleeding
28 days
Re-bleeding
within 28 days of randomisation
3. Need for salvage surgery or radiological intervention
28 days
Need for salvage surgery or radiological intervention
within 28 days of randomisation
4. Blood transfusion - blood or blood component units transfused
28 days
Blood transfusion - blood or blood component units transfused
within 28 days of randomisation
5. Thromboembolic events (myocardial infarction, stroke, pulmonary embolism, deep vein thrombosis)
28 days
Thromboembolic events (myocardial infarction, stroke, pulmonary embolism, deep vein thrombosis)
within 28 days of randomisation
6. Other adverse medical events (including renal failure, significant cardiac event, respiratory failure, hepatic failure, sepsis, pneumonia, seizure)
28 days
Other adverse medical events (including renal failure, significant cardiac event, respiratory failure, hepatic failure, sepsis, pneumonia, seizure)
within 28 days of randomisation
7. Functional status measured using the Katz Index of Independence in Activities of Daily Living
28 days
Functional status measured using the Katz Index of Independence in Activities of Daily Living
within 28 days of randomisation
8. Time spent at an intensive care unit
28 days
Time spent at an intensive care unit
within 28 days of randomisation
9. Length of stay in hospital
28 days
Length of stay in hospital
within 28 days of randomisation
10. Patient status (death, hospital readmission)
Limited to recruiting countries with appropriate databases

[Time Frame: 12 months ]
Patient status (death, hospital readmission)
Limited to recruiting countries with appropriate databases

[Time Frame: within 12 months of randomisation ]
11. Death from haemorrhage
within 28 days of randomisation
Eligibility
Minimum Age: 16 Years 16 Years
Maximum Age:
Sex: All All
Gender Based:
Accepts Healthy Volunteers: NoNo
Criteria:

Inclusion Criteria:

  • adult patients
  • with acute significant upper or lower gastrointestinal bleeding
  • where the responsible clinician is substantially uncertain as to the appropriateness of antifibrinolytic agents in the patient

Exclusion Criteria:

  • The fundamental eligibility criterion is the responsible clinician's 'uncertainty' as to whether or not to use an antifibrinolytic agent in a particular patient with upper or lower gastrointestinal bleeding.
  • There are no other exclusions.

Inclusion Criteria:

  • adult patients
  • with acute significant upper or lower gastrointestinal bleeding
  • where the responsible clinician is substantially uncertain as to the appropriateness of antifibrinolytic agents in the patient

Exclusion Criteria:

  • The fundamental eligibility criterion is the responsible clinician's 'uncertainty' as to whether or not to use an antifibrinolytic agent in a particular patient with upper or lower gastrointestinal bleeding.
  • There are no other exclusions.
Contacts/Locations
Central Contact: Haleema Shakur
Telephone: ++44(0)20 7958 8113
Email: haltit@lshtm.ac.uk
Haleema Shakur
Telephone: ++44(0)20 7958 8113
Email: haltit@lshtm.ac.uk
Study Officials: Haleema Shakur
Study Director
LSHTM
Haleema Shakur
Study Director
LSHTM
Locations: United KingdomUnited Kingdom
Over 50 countries Worldwide
London, United Kingdom
Over 50 countries Worldwide
[Recruiting]
London, United Kingdom
Principal Investigator: Tim Harris, MD
IPDSharing
Plan to Share IPD:
References
Citations:
Links:
Description: Related Info
Description: Trial website
Available IPD/Information:

Scroll up to access the controls Scroll to the Study top

U.S. National Library of Medicine | U.S. National Institutes of Health | U.S. Department of Health & Human Services