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

• ClinicalTrials.gov Identifier: NCT03385928
• Recruitment Status: Recruiting
• First Posted: December 29, 2017
• Last Update Posted: April 1, 2022
• Sponsor: Neuroscience Trials Australia
• Collaborator: The Florey Institute of Neuroscience and Mental Health
• Information provided by (Responsible Party): Neuroscience Trials Australia

Tracking Information

• First Submitted Date: December 13, 2017
• First Posted Date: December 29, 2017
• Last Update Posted Date: April 1, 2022
• Actual Study Start Date: March 19, 2018
• Estimated Primary Completion Date: December 1, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 10, 2021)

Haematoma growth by 24±6 hours as defined by either ≥33%or ≥6ml increase from baseline ICH volume (mls) [ Time Frame: 24 hours(plus or minus 6 hours) ]

Relative ICH haematoma growth

Original Primary Outcome Measures (submitted: December 20, 2017)

Relative ICH haematoma growth at 24±3 hours, adjusted for baseline ICH volume (mls) [ Time Frame: 24 hours(plus or minus 3 hours) ]

Relative ICH haematoma growth

Current Secondary Outcome Measures (submitted: July 27, 2021)

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

Original Secondary Outcome Measures (submitted: December 20, 2017)

• ICH growth [ Time Frame: 24 hours (plus or minus 3 hours) ]
  ICH growth as defined by either 33% or 6ml increase from baseline, adjusted for baseline ICH volume
• Absolute ICH growth (mls) [ Time Frame: 24 hours (plus or minus 3 hours) ]
  Absolute ICH growth
• Relative ICH growth volume (mls) [ Time Frame: 1 hour after baseline CT ]
  Relative and absolute ICH growth volume, adjusted for baseline ICH volume
• Major thromboembolic events [ Time Frame: 3 months ]
  Major thromboembolic events (myocardial infarction, ischaemic stroke, pulmonary embolism) or death
• Intraventricular haematoma growth [ Time Frame: 24 hours (plus or minus 3 hours) ]
  Absolute intraventricular haematoma (IVH) growth volume adjusted for baseline IVH volume
• Modified Rankin Scale (mRS) [ Time Frame: 3 months ]
  mRS 0-4 or back to pre-stroke level, or mRS 0-3 or back to pre-stroke level
• mRS [ Time Frame: 3 months ]
  Categorical shift in mRS

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: STOP-MSU: Stopping Haemorrhage With Tranexamic Acid for Hyperacute Onset Presentation Including Mobile Stroke Units
• Official Title: 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
• Brief Summary: 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.
• 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
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

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.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

• Condition: Intracerebral Haemorrhage

Intervention

• Drug: Tranexamic Acid
  Investigational product given within 2 hours of symptom onset
• Drug: Normal saline
  Placebo given within 2 hours of symptom onset
  Other Name: 0.9%NaCl

Study Arms

• 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.
  Intervention: Drug: Tranexamic Acid
• 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.
  Intervention: Drug: Normal saline

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 10, 2021): 326
• Original Estimated Enrollment (submitted: December 20, 2017): 62
• Estimated Study Completion Date: March 1, 2024
• Estimated Primary Completion Date: December 1, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Henry Zhao, MD; +61 3 9342 7000; henry.zhao@mh.org.au

Contact: Michele Sallaberger; 0438 471 423; michele.sallaberger@florey.edu.au

• Listed Location Countries: Australia, Finland, New Zealand, Taiwan, Vietnam

Administrative Information

• NCT Number: NCT03385928
• Other Study ID Numbers: NTA1702
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Neuroscience Trials Australia
• Original Responsible Party: Same as current
• Current Study Sponsor: Neuroscience Trials Australia
• Original Study Sponsor: Same as current
• 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

• PRS Account: Neuroscience Trials Australia
• Verification Date: March 2022