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

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

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.

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.

2024-04-2026 citations

10.1016/s1474-4422(24)00128-5

Tranexamic Acid for Intracerebral Hemorrhage in Patients on Non-Vitamin K Antagonist Oral Anticoagulants (TICH-NOAC): A Multicenter, Randomized, Placebo-Controlled, Phase 2 Trial

Alexandros A. Polymeris, Grzegorz Marek Karwacki, Bernhard Siepen, Sabine Schaedelin, Dimitrios A. Tsakiris et al. (59 authors)

Stroke2023-07-1934 citations

10.1161/strokeaha.123.042866

Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial.

Sprigg N, Flaherty K, Appleton JP, Al-Shahi Salman R, Bereczki D, Beridze M, Christensen H, Ciccone A, Collins R, Czlonkowska A, Dineen RA, Duley L, Egea-Guerrero JJ, England TJ, Krishnan K, Laska AC, Law ZK, Ozturk S, Pocock SJ, Roberts I, Robinson TG, Roffe C, Seiffge D, Scutt P, Thanabalan J, Werring D, Whynes D, Bath PM, TICH-2 Investigators.

2018-05-16323 citations

10.1016/s0140-6736(18)31033-x

Interventions

DRUGTranexamic Acid

Investigational product given within 2 hours of symptom onset

DRUGNormal saline

Placebo given within 2 hours of symptom onset

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

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.

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

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.

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
The number of patients with mRS 0-3 or back to pre-stroke level at 3 months	90 days ± 7 days	mRS 0-3 or back to pre-stroke level at 3 months
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	24 hours ±6 hours	ICH or IVH growth at 24 hours ±6 hours from baseline
Absolute haematoma growth by 24±6 hours	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	24 hour ±6 hours	Relative ICH growth volume, adjusted for baseline ICH volume
Absolute intraventricular haematoma growth by 24 hours ±6 hours	24 hours ±6 hours	IVH growth at 24 hours ±6 hours from baseline
Absolute intracerebral plus intraventricular haematoma growth by 24±6 hours	24 hours ±6 hours	ICH plus IVH growth from baseline
Categorical shift in mRS at 3 months	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	3 months from baseline	Safety outcome
Death within 3 months	3 months from baseline	Safety outcome
Death within 7 days	7 days from baseline	Safety outcome
The number of patients with mRS 0-4 or back to pre-stroke level at 3 months	90 days ± 7 days	mRS 0-4 or back to pre-stroke level at 3 months

Countries

Australia, Finland, New Zealand, Taiwan, Vietnam

Outcome results

None listed