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Haemorrhage Alleviation With Tranexamic Acid- Intestinal System (HALT-IT)

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ClinicalTrials.gov Identifier: NCT01658124
Recruitment Status : Recruiting
First Posted : August 6, 2012
Last Update Posted : June 21, 2019
Sponsor:
Collaborators:
Rawalpindi Medical University
University of Ibadan
Information provided by (Responsible Party):
London School of Hygiene and Tropical Medicine

Tracking Information
First Submitted Date  ICMJE July 26, 2012
First Posted Date  ICMJE August 6, 2012
Last Update Posted Date June 21, 2019
Actual Study Start Date  ICMJE July 2013
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 24, 2019)
The primary outcome is death from haemorrhage [ Time Frame: within 5 days of randomisation ]
Original Primary Outcome Measures  ICMJE
 (submitted: August 1, 2012)
The primary outcome is death in hospital (cause-specific mortality will also be recorded) [ Time Frame: within 28 days of randomisation ]
Change History Complete list of historical versions of study NCT01658124 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 24, 2019)
  • Death (all cause and cause specific) [ Time Frame: within 28 days of randomisation ]
  • Death from haemorrhage [ Time Frame: within 28 days of randomisation ]
  • Number of Patients with Re-bleeding [ Time Frame: within 5 and 28 days of randomisation ]
  • Number of patients who had Endoscopic, radiological or surgical intervention for gastro intestinal bleeding [ Time Frame: within 28 days of randomisation ]
  • Number of patients who had Blood transfusion [ Time Frame: within 28 days of randomisation ]
    blood or blood component units
  • Number of patients with Thromboembolic events [ Time Frame: within 28 days of randomisation ]
    fatal and non-fatal myocardial infarction, stroke, pulmonary embolism, deep vein thrombosis
  • Number of patients with Other adverse medical events [ Time Frame: within 28 days of randomisation ]
    including renal failure, significant cardiac event, respiratory failure, hepatic failure, sepsis, pneumonia, seizure, other reported events
  • Functional status measured using the Katz Index of Independence in Activities of Daily Living [ Time Frame: within 28 days of randomisation ]
  • Time spent at an intensive care or high dependency unit [ Time Frame: within 28 days of randomisation ]
  • Length of stay in hospital [ Time Frame: within 28 days of randomisation ]
  • Patient status (death, hospital readmission) [ Time Frame: within 12 months of randomisation ]
    Limited to recruiting countries with appropriate databases
Original Secondary Outcome Measures  ICMJE
 (submitted: August 1, 2012)
  • Re-bleeding [ Time Frame: 28 days ]
  • Need for salvage surgery or radiological intervention [ Time Frame: 28 days ]
  • Blood transfusion - blood or blood component units transfused [ Time Frame: 28 days ]
  • Thromboembolic events (myocardial infarction, stroke, pulmonary embolism, deep vein thrombosis) [ Time Frame: 28 days ]
  • Other adverse medical events (including renal failure, significant cardiac event, respiratory failure, hepatic failure, sepsis, pneumonia, seizure) [ Time Frame: 28 days ]
  • Functional status measured using the Katz Index of Independence in Activities of Daily Living [ Time Frame: 28 days ]
  • Time spent at an intensive care unit [ Time Frame: 28 days ]
  • Length of stay in hospital [ Time Frame: 28 days ]
  • Patient status (death, hospital readmission) [ Time Frame: 12 months ]
    Limited to recruiting countries with appropriate databases
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Haemorrhage Alleviation With Tranexamic Acid- Intestinal System
Official Title  ICMJE Tranexamic Acid for the Treatment of Gastrointestinal Haemorrhage: an International Randomised, Double Blind Placebo Controlled Trial
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.
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 from haemorrhage within 5 days of randomisation (all cause and cause-specific mortality will also be recorded).

SECONDARY OUTCOMES:

  1. Re-bleeding
  2. Endoscopic, radiological or surgical 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 and other reported events)
  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 12,000 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Gastrointestinal Bleeding
Intervention  ICMJE
  • Drug: Tranexamic Acid
  • Drug: Placebo
Study Arms  ICMJE
  • Experimental: Tranexamic acid
    (total dose 8 grams)
    Intervention: Drug: Tranexamic Acid
  • Placebo Comparator: Placebo
    (Sodium Chloride 0.9%)
    Intervention: Drug: Placebo
Publications * Roberts I, Coats T, Edwards P, Gilmore I, Jairath V, Ker K, Manno D, Shakur H, Stanworth S, Veitch A. HALT-IT--tranexamic acid for the treatment of gastrointestinal bleeding: study protocol for a randomised controlled trial. Trials. 2014 Nov 19;15:450. doi: 10.1186/1745-6215-15-450.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 29, 2017)
12000
Original Estimated Enrollment  ICMJE
 (submitted: August 1, 2012)
8000
Estimated Study Completion Date  ICMJE October 2020
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Haleema Shakur-Still ++44(0)20 7958 8113 haltit@lshtm.ac.uk
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01658124
Other Study ID Numbers  ICMJE ISRCTN11225767
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party London School of Hygiene and Tropical Medicine
Study Sponsor  ICMJE London School of Hygiene and Tropical Medicine
Collaborators  ICMJE
  • Rawalpindi Medical University
  • University of Ibadan
Investigators  ICMJE
Study Director: Haleema Shakur-Still LSHTM
PRS Account London School of Hygiene and Tropical Medicine
Verification Date December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP