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

NCT ID: NCT03385928

Last Updated: 2023-09-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 201 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-19
• Study Completion Date: 2023-05-28

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.

Conditions

Intracerebral Haemorrhage

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Tranexamic Acid

Intervention Type: DRUG

Investigational product given within 2 hours of symptom onset

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.

Group Type: PLACEBO_COMPARATOR

Normal saline

Intervention Type: DRUG

Placebo given within 2 hours of symptom onset

Interventions

Tranexamic Acid

Investigational product given within 2 hours of symptom onset

Intervention Type: DRUG

Normal saline

Placebo given within 2 hours of symptom onset

Intervention Type: DRUG

Other Intervention Names

0.9%NaCl

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Florey Institute of Neuroscience and Mental Health

OTHER

Sponsor Role: collaborator

Neuroscience Trials Australia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Geoffrey Donnan, MD

Role: PRINCIPAL_INVESTIGATOR

The Florey Institute of Neuroscience and Mental Health

Stephen Davis, MD

Role: PRINCIPAL_INVESTIGATOR

Melbourne Health Dept of Neurology & The University of Melbourne Dept of Medicine

Henry Zhao, MD

Role: PRINCIPAL_INVESTIGATOR

Melbourne Health Dept of Neurology & The University of Melbourne Dept of Medicine

Locations

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Liverpool Hospital

Liverpool, New South Wales, Australia

John Hunter Hospital

New Lambton Heights, New South Wales, Australia

Sunshine Coast University Hospital

Birtinya, Queensland, Australia

Gold Coast University Hospital

Southport, Queensland, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Box Hill Hospital

Box Hill, Victoria, 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

Alfred Hospital

Melbourne, Victoria, Australia

Royal Melbourne Hospital

Melbourne, Victoria, Australia

Mobile Stroke Unit

Parkville, Victoria, Australia

Helsinki University Hospital

Helsinki, , Finland

CDHB Christchurch Hospital

Christchurch, , New Zealand

Palmerston North Hospital

Palmerston North, , New Zealand

Wellington Hospital

Wellington, , New Zealand

E-DA Hospital

Kaohsiung City, Yanchao District, Taiwan

China Medical University Hospital

Taichung, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Bach Mai Hospital

Hanoi, , Vietnam

Military 103 Hospital

Hanoi, , Vietnam

Nguyen Tri Phuong Hospital

Ho Chi Minh City, , Vietnam

Countries

Australia; Finland; New Zealand; Taiwan; Vietnam

References

Yassi N, Zhao H, Churilov L, Wu TY, Ma H, Nguyen HT, Cheung A, Meretoja A, Mai DT, Kleinig T, Jeng JS, Choi PMC, Duc PD, Brown H, Ranta A, Spratt N, Cloud GC, Wang HK, Grimley R, Mahawish K, Cho DY, Shah D, Nguyen TMP, Sharma G, Yogendrakumar V, Yan B, Harrison EL, Devlin M, Cordato D, Martinez-Majander N, Strbian D, Thijs V, Sanders LM, Anderson D, Parsons MW, Campbell BCV, Donnan GA, Davis SM; STOP-MSU Trial Investigators. Tranexamic acid versus placebo in individuals with intracerebral haemorrhage treated within 2 h of symptom onset (STOP-MSU): an international, double-blind, randomised, phase 2 trial. Lancet Neurol. 2024 Jun;23(6):577-587. doi: 10.1016/S1474-4422(24)00128-5. Epub 2024 Apr 20.

Reference Type: DERIVED

PMID: 38648814 (View on PubMed)

Eilertsen H, Menon CS, Law ZK, Chen C, Bath PM, Steiner T, Desborough MJ, Sandset EC, Sprigg N, Al-Shahi Salman R. Haemostatic therapies for stroke due to acute, spontaneous intracerebral haemorrhage. Cochrane Database Syst Rev. 2023 Oct 23;10(10):CD005951. doi: 10.1002/14651858.CD005951.pub5.

Reference Type: DERIVED

PMID: 37870112 (View on PubMed)

Other Identifiers

NTA1702

Identifier Type: -

Identifier Source: org_study_id