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

Intracerebral Haemorrhage Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03385928
• Other study ID #: NTA1702
• Status: Completed
• Phase: Phase 2
• Start date: March 19, 2018
• Est. completion date: May 28, 2023

Study information

• Verified date: September 2023
• Source: Neuroscience Trials Australia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 201
• Est. completion date: May 28, 2023
• Est. primary completion date: May 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cerebral Hemorrhage
• Hemorrhage
• Intracerebral Haemorrhage

Intervention

Drug:
• Tranexamic Acid
Investigational product given within 2 hours of symptom onset
• Normal saline
Placebo given within 2 hours of symptom onset

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Sunshine Coast University Hospital	Birtinya	Queensland
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Monash Medical Centre	Clayton	Victoria
Australia	St Vincent's Hospital Melbourne	Fitzroy	Victoria
Australia	University Hospital Geelong	Geelong	Victoria
Australia	Austin Hospital	Heidelberg	Victoria
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Alfred Hospital	Melbourne	Victoria
Australia	Royal Melbourne Hospital	Melbourne	Victoria
Australia	John Hunter Hospital	New Lambton Heights	New South Wales
Australia	Mobile Stroke Unit	Parkville	Victoria
Australia	Gold Coast University Hospital	Southport	Queensland
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Finland	Helsinki University Hospital	Helsinki
New Zealand	CDHB Christchurch Hospital	Christchurch
New Zealand	Palmerston North Hospital	Palmerston North
New Zealand	Wellington Hospital	Wellington
Taiwan	E-DA Hospital	Kaohsiung City	Yanchao District
Taiwan	China Medical University Hospital	Taichung City
Taiwan	National Taiwan University Hospital	Taipei City
Vietnam	Bach Mai Hospital	Hanoi
Vietnam	Military 103 Hospital	Hanoi
Vietnam	Nguyen Tri Phuong Hospital	Ho Chi Minh City

Sponsors (2)

Lead Sponsor	Collaborator
Neuroscience Trials Australia	The Florey Institute of Neuroscience and Mental Health

Countries where clinical trial is conducted

Australia,  Finland,  New Zealand,  Taiwan,  Vietnam, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Relative haematoma growth by 24±6 hours	Relative ICH growth volume, adjusted for baseline ICH volume	24 hour ±6 hours
Secondary	Absolute intraventricular haematoma growth by 24 hours ±6 hours	IVH growth at 24 hours ±6 hours from baseline	24 hours ±6 hours
Secondary	Absolute intracerebral plus intraventricular haematoma growth by 24±6 hours	ICH plus IVH growth from baseline	24 hours ±6 hours
Secondary	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
Secondary	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
Secondary	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
Secondary	Major thromboembolic events (myocardial infarction, ischaemic stroke, or pulmonary embolism) within 3 months	Safety outcome	3 months from baseline
Secondary	Death within 3 months	Safety outcome	3 months from baseline
Secondary	Death within 7 days	Safety outcome	7 days from baseline