STOP-MSU: Stopping Haemorrhage With Tranexamic Acid for Hyperacute Onset Presentation Including Mobile Stroke Units

STOP-MSU: Stopping Haemorrhage With Tranexamic Acid for Hyperacute Onset Presentation Including Mobile Stroke Units. A Phase II Randomised, Placebo-controlled, Investigator-driven Trial of Tranexamic Acid Within 2 Hours of Intracerebral Haemorrhage

The study is a prospective phase II randomised, double-blind, placebo-controlled investigator-driven trial in acute intracerebral haemorrhage patients. The study has 2 arms with 1:1 randomisation to either intravenous tranexamic acid or placebo and will test the hypothesis that in patients with spontaneous ICH, treatment with tranexamic acid within 2 hours of onset will reduce haematoma expansion compared to placebo.

Study Overview

• Status: Completed
• Conditions: Intracerebral Haemorrhage
• Intervention / Treatment: Drug: Tranexamic Acid; Drug: Normal saline

Detailed Description

The trial will include patients with acute spontaneous ICH, who are ≥18 years of age and are eligible for treatment within 2 hours of stroke onset. A sample size of 326 patients is calculated to give 80% power to detect a large effect size assuming mean relative ICH haematoma growth of 38% in the placebo arm compared to 19% in the active treatment arm and standard deviation of 19%, inflated for nonparametric analysis. Adaptive increase in sample size will be performed if the result of interim analysis of the first 144 patients is promising, using the methodology of Mehta and Pocock. The maximum sample size is capped at 326. Standard CT for initial diagnosis of suspected stroke patients will be performed. Neurological impairment and functional scores will be measured by a neurologist or health care professional trained in their administration. The assessors will be blinded to the treatment group. Patients eligible for the RCT will be randomised in a 1:1 ratio to receive either tranexamic acid or placebo stratified by treating centre and utilising randomly permuted blocks of random size.

• Study Type: Interventional
• Enrollment (Actual): 201
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital
    • New Lambton Heights, New South Wales, Australia, 2305
      • John Hunter Hospital
  • Queensland
    • Birtinya, Queensland, Australia, 4575
      • Sunshine Coast University Hospital
    • Southport, Queensland, Australia, 4215
      • Gold Coast University Hospital
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre
    • Fitzroy, Victoria, Australia, 3065
      • St Vincent's Hospital Melbourne
    • Geelong, Victoria, Australia, 3220
      • University Hospital Geelong
    • Heidelberg, Victoria, Australia, 3084
      • Austin Hospital
    • Melbourne, Victoria, Australia, 3004
      • Alfred Hospital
    • Melbourne, Victoria, Australia
      • Royal Melbourne Hospital
    • Parkville, Victoria, Australia, 3050
      • Mobile Stroke Unit
• Finland
  • Helsinki, Finland
    • Helsinki University Hospital
• New Zealand
  • Christchurch, New Zealand, 8140
    • CDHB Christchurch Hospital
  • Palmerston North, New Zealand, 4442
    • Palmerston North Hospital
  • Wellington, New Zealand, 6021
    • Wellington Hospital
• Taiwan
  • Taichung City, Taiwan, 40447
    • China Medical University Hospital
  • Taipei City, Taiwan, 100
    • National Taiwan University Hospital
  • Yanchao District
    • Kaohsiung City, Yanchao District, Taiwan
      • E-DA Hospital
• Vietnam
  • Hanoi, Vietnam
    • Bach Mai hospital
  • Hanoi, Vietnam
    • Military 103 Hospital
  • Ho Chi Minh City, Vietnam
    • Nguyen Tri Phuong Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients presenting with an acute ICH
2. Age ≥18 years
3. Treatment can commence within 2 hours of symptom onset (or in patients with unknown time of symptom onset, the time patient was last known to be well)
4. Consent can be obtained from participant or person responsible. When emergency treatment procedures have been followed the participant or person responsible will be asked for consent to continue in the study.

Exclusion Criteria:

1. Glasgow coma scale (GCS) total score of <8
2. Brainstem ICH
3. ICH volume >70 ml as measured by the ABC/2 method
4. ICH known or suspected by study investigator to be secondary to trauma, aneurysm, vascular malformation, haemorrhagic transformation of ischaemic stroke, cerebral venous thrombosis, thrombolytic therapy, tumour, or infection
5. Any history or current evidence suggestive of venous or arterial thrombotic events within the previous 12 months, including clinical, ECG, laboratory, or imaging findings. Clinically silent chance findings of old ischemia are not considered exclusion.
6. Hereditary or acquired haemorrhagic diathesis or coagulation factor deficiency.
7. Use of heparin, low-molecular weight heparin, GPIIb/IIIa antagonist, or oral anticoagulation (e.g. warfarin, factor Xa inhibitor, thrombin inhibitor) within the previous 72 hours.
8. Pregnancy (women of childbearing potential must be tested)
9. Planned surgery for ICH within 24 hours
10. Concurrent or planned treatment with haemostatic agents (e.g. prothrombin complex concentrate, vitamin K, fresh frozen plasma, or platelet transfusion)
11. Participation in any investigational study in the last 30 days
12. Known terminal illness or planned withdrawal of care or comfort care measures
13. Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tranexamic acid; Intravenous tranexamic acid 1000 mg in 100 mL 0.9% NaCl (or in 50ml syringe with 0.9% NaCl) over 10 minutes followed by 1000 mg in 500 mL 0.9% NaCl infusion over 8 hours.	Drug: Tranexamic Acid; Investigational product given within 2 hours of symptom onset
Placebo Comparator: Normal Saline (0.9% NaCl); 100 mls (or in 50ml syringe) intravenous 0.9%NaCl over 10 minutes followed by 500 ml intravenous 0.9% NaCl infusion over 8 hours.	Drug: Normal saline; Placebo given within 2 hours of symptom onset; Other Names: 0.9%NaCl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Haematoma growth by 24±6 hours as defined by either ≥33%or ≥6ml increase from baseline ICH volume (mls)	Relative ICH haematoma growth	24 hours(plus or minus 6 hours)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Haematoma growth by 24±6 hours as defined by ≥33%or ≥6ml increase from baseline in intracerebral haematoma volume, or any increase intraventricular haematoma volume	ICH or IVH growth at 24 hours ±6 hours from baseline	24 hours ±6 hours
Absolute haematoma growth by 24±6 hours	ICH growth as defined by either ≥33%or ≥6ml increase from baseline from baseline, adjusted for baseline ICH volume	24 hours ±6 hours
Relative haematoma growth by 24±6 hours	Relative ICH growth volume, adjusted for baseline ICH volume	24 hour ±6 hours
Absolute intraventricular haematoma growth by 24 hours ±6 hours	IVH growth at 24 hours ±6 hours from baseline	24 hours ±6 hours
Absolute intracerebral plus intraventricular haematoma growth by 24±6 hours	ICH plus IVH growth from baseline	24 hours ±6 hours
The number of patients with mRS 0-3 or back to pre-stroke level at 3 months	mRS 0-3 or back to pre-stroke level at 3 months	90 days ± 7 days
The number of patients with mRS 0-4 or back to pre-stroke level at 3 months	mRS 0-4 or back to pre-stroke level at 3 months	90 days ± 7 days
Categorical shift in mRS at 3 months	mRS 0-4 or back to pre-stroke level, or mRS 0-3 or back to pre-stroke level (with lowest mRS score being the better outcome)	90 days ± 7 days
Major thromboembolic events (myocardial infarction, ischaemic stroke, or pulmonary embolism) within 3 months	Safety outcome	3 months from baseline
Death within 3 months	Safety outcome	3 months from baseline
Death within 7 days	Safety outcome	7 days from baseline

Collaborators and Investigators

• Sponsor: Neuroscience Trials Australia
• Collaborators: The Florey Institute of Neuroscience and Mental Health
• Investigators: Principal Investigator: Geoffrey Donnan, MD, The Florey Institute of Neuroscience and Mental Health; Principal Investigator: Stephen Davis, MD, Melbourne Health Dept of Neurology & The University of Melbourne Dept of Medicine; Principal Investigator: Henry Zhao, MD, Melbourne Health Dept of Neurology & The University of Melbourne Dept of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2018
• Primary Completion (Actual): May 28, 2023
• Study Completion (Actual): May 28, 2023

Study Registration Dates

• First Submitted: December 13, 2017
• First Submitted That Met QC Criteria: December 20, 2017
• First Posted (Actual): December 29, 2017

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 25, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Stroke; Vascular Diseases; Cardiovascular Diseases; Nervous System Diseases; ICH; Central Nervous System Diseases; Tomography, X-Ray Computed; Pharmacologic Actions; Contrast Media; Brain Diseases; Therapeutic Uses; Tranexamic Acid; Angiography; Cerebrovascular Disorders; Cardiovascular Agents; Hemostatics; Antifibrinolytic Agents; Hematologic Agents; Fibrin Modulating Agents; Cerebral Angiography
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Cerebral Hemorrhage; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: NTA1702

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No