Indian Trial of Tranexamic Acid in Spontaneous Intracerebral Haemorrhage

Study Overview
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Brief Summary
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This multicenter, pragmatic randomized, open-label clinical trial aims to assess whether Tranexamic Acid improves outcomes in adult patients with spontaneous intracerebral haemorrhage. The participants presenting within 4.5 hours of the onset of symptoms of stroke with intracerebral haemorrhage confirmed on Computed Tomography (CT Scan) will be randomized into two groups in a 1:1 ratio using a central online randomization. The treatment arm will consist of giving intravenously 2 grams of Tranexamic Acid in 100 ml 0.9% sodium chloride administered over 45 minutes. Control arm patients will receive standard of care treatment as per the institutional protocol. In both arms, intensive systolic blood pressure reduction to less than 140 mmHg will be done using antihypertensive medications, which has to be achieved within one hour and will be maintained over next seven days. The choice of antihypertensive drug will depend on the clinician's preference. Both groups will have a repeat CT scan after 24 hours to check for any increase in the haematoma volume. Any deterioration in the neurological status will warrant urgent brain imaging. On day 7, the patient will be assessed for their NIHSS score and mRS score. On day 90, quality of life and the functional outcome will be assessed.

Detailed Description
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Global Burden of Disease, Injury and Risk factors for hemorrhagic stroke 2010 estimated the burden of spontaneous intracranial haemorrhage (sICH) in India is profound (32 -49%) and it is associated with high mortality (up to 63 %) due to haematoma expansion which occurs in 38% of ICH within first few hours of presentation. Early administration of haemostatic drugs has been used in patients with trauma and was associated with improved outcomes. Similarly, if haemostatic drugs are administered early, which can be a simple and cost-effective intervention, may improve the functional outcomes in patients with sICH. Recently, the TICH 2 trial, which was done to see the effectiveness of the administration of tranexamic acid on hematoma expansion and functional outcomes at three months in patients who presented with sICH within 8 hours of presentation of symptoms onset, showed a decrease in haematoma expansion but no improvement in functional outcome at 90 days. Further larger randomized control trials are required to ascertain the effect of early administration of TXA in sICH. In India patients present to hospitals in the early stages that have developed symptoms after sICH and we propose to study the effect of intravenous Tranexamic Acid for hyperacute primary intracerebral haemorrhage within 4.5 hours of sICH. Trial Population: This multi-centric study will be conducted at 50 stroke centres in India associated with the INSTRuCT Network. All patients presenting with symptoms of stroke to the hospital and admitted to the stroke units will be screened for eligibility and if met, will be included in the study. The INTRINSIC trial intends to recruit 3400 patients. Trial Design: INTRINSIC Trial will be a multicenter, randomized, open-label, clinical trial. The participants will be randomized into two groups in a 1:1 ratio using a central database of INSTRuCT central online randomization. The baseline characteristics will be adjusted to stroke severity using the NIHSS score and the volume of haematoma. The treatment arm will consist of giving intravenously 2 grams of Tranexamic Acid in 100 ml sodium chloride 0.9 % administered over 45 minutes. Control arm patients will receive standard of care management as per the institutional protocol. Both groups will have a repeat CT scan after 24 hours to check for any increase in the haematoma volume. Any deterioration in the GCS will warrant urgent brain CT scans. Antihypertensive drugs used and their doses to control BP will be recorded for up to 7 days. On day 7, the patient will be assessed for their NIHSS score and mRS score. On day 90, quality of life and the functional outcome will be assessed. The need for this study: The proportion of ICH is high in India and other LMIC's, particularly in Asia. Currently, there are no effective treatments available for sICH. Moreover, Tranexamic Acid is cheap, easily available and easy to administer.

Official Title
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Indian Trial of Tranexamic Acid in Spontaneous Intracerebral Haemorrhage

Conditions
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Intracerebral Hemorrhagic Stroke

Intervention / Treatment
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* Drug: Tranexamic acid injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients aged more than 18 years, presenting with non- traumatic intracerebral haemorrhage within 4.5 hours of onset of stroke symptoms Exclusion Criteria: Patients with intracerebral haemorrhage secondary to anticoagulation, thrombolysis, known underlying structural abnormality such as arteriovenous malformation, aneurysm, tumour or venous thrombosis or due to known hereditary coagulation disorders. An underlying structural abnormality does not need to be excluded before enrolment, but where known, patients should not be recruited. Known allergies to Tranexamic Acid. Premorbid modified Rankin scale score >4 at the time of enrollment. Concurrent participation in another drug or device trial. Pre stroke life expectancy <3 months (e.g. advanced metastatic cancer). Glasgow coma scale <7. ICH secondary to trauma. Women pregnant, or breastfeeding at randomization. Planned surgery for ICH within 24 hours. Concurrent or planned treatment with any other haemostatic agents. ICH volume > 60 ml as measured by the ABC/2 method on CT Scan

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicentric, randomized, open-label, clinical trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention Arm<br>The treatment arm will consist of giving intravenously 2 grams of Tranexamic Acid in 100 ml sodium chloride 0.9 % adminsitered over 45 minutes. Intensive systolic blood pressure reduction to less than 140 mmHg will be done using antihypertensive agents (intravenous and/or oral) which is to be achieved within one hour and has to be maintained over seven days. BP monitoring is done for every 15 minutes in the first hour and thereafter every hour for the next six hours after the initiation of intensive BP control. The choice of antihypertensive will depend on the clinician's preference. | Drug: Tranexamic acid injection<br>* The treatment arm will consist of giving intravenously 2 grams of Tranexamic Acid in 100 ml sodium chloride 0.9 % administered over 45 minutes.<br>* Other names: Injection Tramix 500 mg/5 ml;|
| No Intervention: Control Arm<br>The control arm will receive a standard of care management as per the institutional practice. Intensive systolic blood pressure reduction to less than 140 mmHg will be done using antihypertensive (intravenous and/or oral) which is to be achieved within one hour and has to be maintained over seven days. BP monitoring is done for every 15 minutes in the first hour and thereafter every hour for the next six hours after the initiation of intensive BP control. The choice of antihypertensive will depend on the clinician's preference. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death | Death at day 7 | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in hematoma volume | Radiological (CT scan): Change in hematoma volume from baseline to 24 hours scan, hematoma location and new infraction | 24 hours | 
| Neurological impairment | Neurological impairment (NIHSS) at day 7 (or discharge if sooner) | 7 days | 
| modified Rankin Scale (mRS) | Dependency using the seven-level modified Rankin Scale (mRS) at day 90 | 90 days | 
| Quality of life EQ-5D | Quality of life (EQ-5D) at day 90 | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stroke, Spontaneous Intracerebral Haemorrhage, Tranexamic acid