Clinical trial NCT03385928: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Intracerebral Haemorrhage
Keywords: ICH
Stroke
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Tranexamic Acid
Antifibrinolytic Agents
Fibrin Modulating Agents
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Hematologic Agents
Hemostatics
Contrast Media
Angiography
Cerebral Angiography
Tomography, X-Ray Computed
Lead sponsor: Neuroscience Trials Australia
Sponsor class: OTHER
Collaborators: name: The Florey Institute of Neuroscience and Mental Health
First posted: 2017-12-29
Enrollment: 201
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Haematoma growth by 24±6 hours as defined by either ≥33%or ≥6ml increase from baseline ICH volume (mls)
timeFrame: 24 hours(plus or minus 6 hours)
Secondary outcomes:
measure: 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
timeFrame: 24 hours ±6 hours
measure: Absolute haematoma growth by 24±6 hours
timeFrame: 24 hours ±6 hours
measure: Relative haematoma growth by 24±6 hours
timeFrame: 24 hour ±6 hours
measure: Absolute intraventricular haematoma growth by 24 hours ±6 hours
timeFrame: 24 hours ±6 hours
measure: Absolute intracerebral plus intraventricular haematoma growth by 24±6 hours
timeFrame: 24 hours ±6 hours
measure: The number of patients with mRS 0-3 or back to pre-stroke level at 3 months
timeFrame: 90 days ± 7 days
measure: The number of patients with mRS 0-4 or back to pre-stroke level at 3 months
timeFrame: 90 days ± 7 days
measure: Categorical shift in mRS at 3 months
timeFrame: 90 days ± 7 days
measure: Major thromboembolic events (myocardial infarction, ischaemic stroke, or pulmonary embolism) within 3 months
timeFrame: 3 months from baseline
measure: Death within 3 months
timeFrame: 3 months from baseline
measure: Death within 7 days
timeFrame: 7 days from baseline
Other outcomes:
Locations:
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: New Lambton Heights
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: Birtinya
country: Australia
facility: Sunshine Coast University Hospital
state: Queensland
city: Southport
country: Australia
facility: Gold Coast University Hospital
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Fitzroy
country: Australia
facility: St Vincent's Hospital Melbourne
state: Victoria
city: Geelong
country: Australia
facility: University Hospital Geelong
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Parkville
country: Australia
facility: Mobile Stroke Unit
state: Victoria
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Christchurch
country: New Zealand
facility: CDHB Christchurch Hospital
city: Palmerston North
country: New Zealand
facility: Palmerston North Hospital
city: Wellington
country: New Zealand
facility: Wellington Hospital
city: Kaohsiung City
country: Taiwan
facility: E-DA Hospital
state: Yanchao District
city: Taichung City
country: Taiwan
facility: China Medical University Hospital
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
city: Hanoi
country: Vietnam
facility: Bach Mai Hospital
city: Hanoi
country: Vietnam
facility: Military 103 Hospital
city: Ho Chi Minh City
country: Vietnam
facility: Nguyen Tri Phuong Hospital
Study officials:
affiliation: The Florey Institute of Neuroscience and Mental Health
name: Geoffrey Donnan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Melbourne Health Dept of Neurology & The University of Melbourne Dept of Medicine
name: Stephen Davis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Melbourne Health Dept of Neurology & The University of Melbourne Dept of Medicine
name: Henry Zhao, MD
role: PRINCIPAL_INVESTIGATOR
References: