E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Gastrointestinal hemorrhage |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10017960 |
E.1.2 | Term | Gastrointestinal hemorrhage |
E.1.2 | System Organ Class | 100000004856 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The HALT-IT trial will find out whether early administration of tranexamic acid improves outcomes for people who suffered of significant gastrointestinal bleeding. The main outcome is death from haemorrhage within 5 days of randomisation. We will also assess the cause of death. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives will be to assess death from haemorrhage within 28 days of randomisation, all-cause mortality and cause-specific mortality within 28 days of randomisation, and whether tranexamic acid leads to better outcomes such as reducing re-bleeding, need for endoscopy, surgery or radiological intervention, blood transfusion, number of days spent in intensive care. We will also assess whether there is any increase in serious outcomes including heart attack, stroke and blood clots in the legs or lungs, and seizures. In addition, we will evaluate if there is an improvement in patient's ability to perform the activities of daily living at discharge (bathing, dressing, toileting, transferring, continence and feeding) and patients' health status after 1 year. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
• Adult (16 years and over) with significant gastrointestinal bleeding • Where the responsible clinician is substantially uncertain as to whether or not to use tranexamic acid
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E.4 | Principal exclusion criteria |
• Patients for whom the responsible clinician considers there is a clear indication for tranexamic acid. • Patients for whom the responsible clinician considers there is a clear contraindication for tranexamic acid.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome is death from haemorrhage within 5 days after randomisation (all-cause and cause-specific mortality will also be recorded). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
28 days after randomisation, at hospital discharge, or at death whichever occurs first). |
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E.5.2 | Secondary end point(s) |
a) Death from haemorrhage within 28 days of randomisation b) Mortality: all-cause and cause-specific mortality within 28 days of randomisation c) Re-bleeding d) Need for endoscopy, surgery or radiological intervention e) Blood product transfusion f) Thromboembolic events (deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction) g) Other complications (including other significant cardiac event, sepsis, pneumonia, respiratory failure, renal failure, liver failure, seizures) h) Functional status will be measured by the Katz Index of Independence in Activities of Daily Living at discharge from the randomising hospital or in-hospital at 28 days after randomisation. The Index assesses adequacy of performance in six functions of bathing, dressing, toileting, transferring, continence and feeding. Patients are scored ‘yes’ or ‘no’ for independence in each of the functions (score of 6=full function, 4=moderate impairment, and ≤2=severe functional impairment) i) Days spent in intensive care unit or high dependency unit j) Patient status (death, hospital readmission) at 12 months |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
28 days after randomisation, at discharge from the randomising hospital, or at death (whichever occurs first) for all the above secondary outcome, except (j) "Patient status (death, hospital readmission) at 12 months", which will be evaluated at 12 months after randomisation. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 150 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 300 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Albania |
Australia |
Belgium |
Egypt |
Georgia |
India |
Ireland |
Italy |
Jamaica |
Mexico |
Nigeria |
Pakistan |
Romania |
Saudi Arabia |
Spain |
Sudan |
Uganda |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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After 12,000 patients have been recruited (anticipated to be completed by 30/09/2019), the trial will end when follow-up (12 months) of the last patient recruited in the UK is completed.
The trial may be terminated early by the Trial Steering Committee on the recommendation of the Independent Data Monitoring Committee on their interim reviews of the unblinded data. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 31 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 30 |