Clinical trial NCT03044184: Tranexamic Acid for Spontaneous Acute Cerebral Hemorrhage Trial
Official title: Randomized, Double-blind, Placebo-controlled Trial to Investigate the Effectiveness of Early Intravenous Tranexamic Acid in Limiting Hematoma Expansion in Patients With Spontaneous Intracerebral Hemorrhage
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Stroke Hemorrhagic
Intracerebral Haemorrhage
Keywords: Tranexamic Acid
Antifibrinolytic
Lead sponsor: Kwong Wah Hospital
Sponsor class: OTHER
First posted: 2017-02-06
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised placebo-controlled parallel group clinical trial
Primary purpose: TREATMENT

Brief summary: This study aims to explore the effectiveness of tranexamic acid (also known as trans amine or TXA) in reducing hematoma expansion in patients with hemorrhagic stroke when given in the acute phase.

METHODOLOGY

This will be a Phase III, parallel-group double-blind randomised placebo control trial. Patients allocated to the control group will receive standard care for hemorrhagic stroke according to the 2015 American Heart Association guidelines. Patients allocated to the intervention group will receive, in addition to standard care, a loading dose of intravenous TXA 1gm within 3 hours of symptom onset followed by a 1gm maintenance dose over 8 hours. Timing and dosing are in accordance to previous established study protocols. Patients in the intervention group will only receive a single treatment course of TXA.

Study subjects will be identified by either the on-duty clinicians from the Department of Neurosurgery of this institution or by the study investigators. Should the patient meet study eligibility criteria consent will be obtained either from the patient or from his/her next of kin. 1:1 block randomization will be performed by a remote internet randomization service by accessing a website. Patients allocated to the intervention arm will have 1gm of TXA added to 100ml of normal saline (0.9%) infused over 10 minutes as a loading dose. This is then followed by a maintenance dose of 1gm of TXA in 500ml of intravenous isotonic solution infused at 120mg/hour (60ml/hour) for 8 hours. Patient's allocated to the control arm will have an equal volume of normal saline (0.9%) infused as a placebo. The patient and the outcome assessor will be blinded to study group allocation.

The primary endpoint of this study will be to assess the percentage change in brain blood clot volume by computed tomography brain scans on admission, 6 hours later, at 24 hours and at 1 week.

Detailed description: INTRODUCTION

There are very few treatment options for patients with spontaneous intracerebral hemorrhage, a type of hemorrhagic stroke especially prevalent among Chinese, during the acute phase. Blood clot expansion in the brain (hematoma expansion; HE) is one of the most significant predictors for poor outcome in such patients.

Tranexamic acid (TXA) is a commonly used medication available in all acute Hospital Authority hospitals prescribed for a variety of conditions when bleeding occurs, for example epistaxis and menorrhagia. Intravenous administration of TXA has been proven to benefit severe trauma patients by reducing mortality and also preventing the recurrent rupture of brain aneurysms in another type of hemorrhagic stroke. The medication is safe and has been proven to improve outcomes in these patients.

A previously performed pilot study exploring the safety and feasibility of administrating intravenous TXA to patients with hemorrhagic stroke was recently performed and concluded the medication's safety. There was also a trend to significance for reducing the percentage change of hematoma volume in patients who received TXA.

This study aims to explore the effectiveness of TXA in reducing hematoma expansion in patients with hemorrhagic stroke when given in the acute phase.

METHODOLOGY

This will be a Phase III, parallel-group double-blind randomised placebo control trial. Patients allocated to the control group will receive standard care for hemorrhagic stroke according to the 2015 American Heart Association guidelines. Patients allocated to the intervention group will receive, in addition to standard care, a loading dose of intravenous TXA 1gm within 3 hours of symptom onset followed by a 1gm maintenance dose over 8 hours. Timing and dosing are in accordance to previous established study protocols. Patients in the intervention group will only receive a single treatment course of TXA.

Study subjects will be identified by either the on-duty clinicians from the Department of Neurosurgery of this institution or by the study investigators. Should the patient meet study eligibility criteria consent will be obtained either from the patient or from his/her next of kin. 1:1 block randomization will be performed by a remote internet randomization service by accessing a website. Patients allocated to the intervention arm will have 1gm of TXA added to 100ml of normal saline (0.9%) infused over 10 minutes as a loading dose. This is then followed by a maintenance dose of 1gm of TXA in 500ml of intravenous isotonic solution infused at 120mh/hour (60ml/hour) for 8 hours. Patient's allocated to the control arm will have an equal volume of isotonic solution infused as a placebo. The patient and the outcome assessor will be blinded to study group allocation.

The primary endpoint of this study will be to assess the percentage change in brain blood clot volume by computed tomography brain scans on admission, 6 hours later, at 24 hours and at 1 week. Volumetric analysis of the brain scans will be performed by two radiologists blinded to the patient's study group allocation..

Secondary endpoints will be assessed by a research assistant blinded to the patient's study group allocation. One such endpoint is functional outcome in terms of the Glasgow Outcome Scale and modified Rankin scale at 3 months and 6 months after stroke. Another secondary endpoint is quality of life at 3 months and 6 months by adopting the Stroke-specific Quality of Life Scale. Other secondary endpoints include death within 30 days of admission, vascular occlusive events (myocardial infarction, pulmonary embolism, deep vein thrombosis), ischemic stroke, seizures and other TXA-associated adverse effects.

Eligibility criteria: Inclusion Criteria:

1. Patients with CT evidence of supratentorial intracerebral hemorrhage
2. Initiation of trial medication within 3 hours from the time of symptoms onset.
3. Ethnic Chinese
4. Reasonable expectation of completion of outcome measures at follow-up
5. Written informed consent from either the patient or next-of-kin or legal guardian.

Exclusion Criteria:

1. Patients not expected to survive 24 hours after admission.
2. Patients with brainstem herniation syndrome on admission.
3. Patients who need immediate neurosurgical intervention.
4. GCS of of 5 or less on admission i.e. a GCS score of 2 according to the Hemphil ICH score1.
5. Previous antiplatelet and anticoagulant medication use.
6. Known thrombocytopenia or coagulopathy.
7. Disseminated intravascular coagulation on admission.
8. Acute sepsis on admission.
9. Intracerebral hemorrhage (ICH) secondary to intracranial vascular lesion: aneurysm, arteriovenous malformation, neoplasm or dural venous sinus thrombosis.
10. Previous venous thromboembolic disease : deep venous thrombosis.
11. History of ischemic stroke or transient ischemic attack within 12 months.
12. History of ischemic heart disease or myocardial infarction.
13. History of peripheral vascular disease.
14. Patients with previous disability (prestroke modified Rankin scale score \>2)
15. Pregnancy or breast feeding.
16. History of allergy to tranexamic acid

Primary outcomes:
measure: Intracerebral hematoma volume (by computed tomography brain scan) at 6 hours
timeFrame: At 6 hours
measure: Intracerebral hematoma volume (by computed tomography brain scan) at 24 hours
timeFrame: At 24 hours
measure: Intracerebral hematoma volume (by computed tomography brain scan) at 1 week
timeFrame: At 1 week
Secondary outcomes:
measure: Glasgow outcome score
timeFrame: At 3-months and 6 months after stroke
measure: Modified Rankin score
timeFrame: At 3-months and 6 months after stroke
measure: Stroke-specific quality of life scale
timeFrame: At 3-months and 6 months after stroke
measure: 30-day mortality
timeFrame: At 30 days after admission or until time of death within 30 days
measure: Vascular occlusive events
timeFrame: At 30 days after admission
measure: Rate of seizures
timeFrame: At 30 days after stroke
measure: Tranexamic acid-associated adverse effects
timeFrame: At 30 days after admission
measure: Need for neurosurgical intervention
timeFrame: At 30 days after admission
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Kwong Wah Hospital
Study officials:
affiliation: Neurosurgery, Kwong Wah Hospital
name: Peter YM Woo, FRCS
role: PRINCIPAL_INVESTIGATOR
References: