Tranexamic Acid for Spontaneous Acute Cerebral Hemorrhage Trial

Stroke Hemorrhagic Clinical Trial

— TRANSACT  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03044184
• Other study ID #: KwongWH
• Status: Recruiting
• Phase: Phase 3
• Start date: April 1, 2017
• Est. completion date: December 31, 2020

Study information

• Verified date: October 2019
• Source: Kwong Wah Hospital
• Contact: Peter YM Woo, FRCS
• Phone: 3517 5052
• Email: wym307[@]ha.org.hk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 220
• Est. completion date: December 31, 2020
• Est. primary completion date: June 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Cerebral Hemorrhage
• Hemorrhage
• Intracerebral Haemorrhage
• Stroke Hemorrhagic

Intervention

Drug:
• Tranexamic Acid
Transamine is an antifibrinolytic medication given systemically via the intravenous route

Locations

Country	Name	City	State
Hong Kong	Kwong Wah Hospital	Hong Kong

Sponsors (1)

Lead Sponsor	Collaborator
Kwong Wah Hospital

Country where clinical trial is conducted

Hong Kong, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Intracerebral hematoma volume (by computed tomography brain scan) at 6 hours	Intracerebral hematoma volume (ml) as assessed by CT brain scan.	At 6 hours
Primary	Intracerebral hematoma volume (by computed tomography brain scan) at 24 hours	Intracerebral hematoma volume (ml) as assessed by CT brain scan.	At 24 hours
Primary	Intracerebral hematoma volume (by computed tomography brain scan) at 1 week	Intracerebral hematoma volume (ml) as assessed by CT brain scan.	At 1 week
Secondary	Glasgow outcome score		At 3-months and 6 months after stroke
Secondary	Modified Rankin score		At 3-months and 6 months after stroke
Secondary	Stroke-specific quality of life scale		At 3-months and 6 months after stroke
Secondary	30-day mortality	All-cause mortality within 30 days of admission	At 30 days after admission or until time of death within 30 days
Secondary	Vascular occlusive events	Ischemic stroke, myocardial infarction, pulmonary embolism, deep vein thrombosis	At 30 days after admission
Secondary	Rate of seizures	Rate of seizures within 30 days of stroke	At 30 days after stroke
Secondary	Tranexamic acid-associated adverse effects	Intolerable gastrointestinal symptoms such as dyspepsia, diarrhea, vomiting.; Allergic reaction to TXA.	At 30 days after admission
Secondary	Need for neurosurgical intervention	Need for operative management of the hemorrhagic stroke	At 30 days after admission