Tranexamic Acid for Spontaneous Acute Cerebral Hemorrhage Trial (TRANSACT)

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

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.

Study Overview

• Status: Unknown
• Conditions: Stroke Hemorrhagic; Intracerebral Haemorrhage
• Intervention / Treatment: Drug: Tranexamic Acid

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.

• Study Type: Interventional
• Enrollment (Anticipated): 220
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Peter YM Woo, FRCS; Phone Number: 3517 5052; Email: wym307@ha.org.hk
• Study Contact Backup: Name: Carmen Ho; Email: hoht@ha.org.hk

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • Kwong Wah Hospital
    • Contact: Peter YM Woo, MBBS, FRCS; Phone Number: 3517 5052; Email: wym@ha.org.hk
    • Contact: Ho

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intervention; Standard management for patients with spontaneous intracerebral hemorrhage according to 2015 AHA/ASA Guidelines for the Management of Intracerebral Hemorrhage AND Patients will have 1gram of tranexamic acid (diluted in 100ml of normal saline 0.9%) intravenously infused over 10 minutes within 3 hours of symptom presentation and another 1 gram of tranexamic acid (diluted in 100ml of normal saline 0.9%) infused over 8 hours.	Drug: Tranexamic Acid; Transamine is an antifibrinolytic medication given systemically via the intravenous route; Other Names: Transamine
No Intervention: Control; Standard management for patients with spontaneous intracerebral hemorrhage according to 2015 AHA/ASA Guidelines for the Management of Intracerebral Hemorrhage AND Patients will 100ml of normal saline 0.9% intravenously infused over 10 minutes within 3 hours of symptom presentation and another 100ml of normal saline 0.9% infused over 8 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracerebral hematoma volume (by computed tomography brain scan) at 6 hours	Intracerebral hematoma volume (ml) as assessed by CT brain scan.	At 6 hours
Intracerebral hematoma volume (by computed tomography brain scan) at 24 hours	Intracerebral hematoma volume (ml) as assessed by CT brain scan.	At 24 hours
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glasgow outcome score		At 3-months and 6 months after stroke
Modified Rankin score		At 3-months and 6 months after stroke
Stroke-specific quality of life scale		At 3-months and 6 months after stroke
30-day mortality	All-cause mortality within 30 days of admission	At 30 days after admission or until time of death within 30 days
Vascular occlusive events	Ischemic stroke, myocardial infarction, pulmonary embolism, deep vein thrombosis	At 30 days after admission
Rate of seizures	Rate of seizures within 30 days of stroke	At 30 days after stroke
Tranexamic acid-associated adverse effects	Intolerable gastrointestinal symptoms such as dyspepsia, diarrhea, vomiting.; Allergic reaction to TXA.	At 30 days after admission
Need for neurosurgical intervention	Need for operative management of the hemorrhagic stroke	At 30 days after admission

Collaborators and Investigators

• Sponsor: Kwong Wah Hospital
• Investigators: Principal Investigator: Peter YM Woo, FRCS, Neurosurgery, Kwong Wah Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2017
• Primary Completion (Anticipated): June 30, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: January 26, 2017
• First Submitted That Met QC Criteria: February 2, 2017
• First Posted (Estimate): February 6, 2017

Study Record Updates

• Last Update Posted (Actual): October 17, 2019
• Last Update Submitted That Met QC Criteria: October 15, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Tranexamic Acid; Antifibrinolytic
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Intracranial Hemorrhages; Hemorrhage; Cerebral Hemorrhage; Hemorrhagic Stroke; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Fibrin Modulating Agents; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; Anti-Anxiety Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Monoamine Oxidase Inhibitors; Tranexamic Acid; Tranylcypromine
• Other Study ID Numbers: KwongWH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No