STOP-AUST: The Spot Sign and Tranexamic Acid On Preventing ICH Growth - AUStralasia Trial

NCT01702636 | Completed Phase 2 DMC

• 1 other identifier: NTA1201
• Study Type: interventional
• Target: 100
• Locations: 2 countries
• Sites: 11

Brief Summary

The aim of the study is to test if intracerebral haemorrhage (ICH) patients who have contrast extravasation on computed tomography angiography, the "spot sign", have lower rates of haematoma growth when treated with tranexamic acid within 4.5 hours of stroke onset, compared to placebo.

Conditions

Intracerebral Haemorrhage; Stroke

Keywords

Intracerebral Hemorrhage; 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

Outcome Measures

Primary Outcomes (1)

• ICH growth by 24±3 hours as defined by either 33% or 6 ml increase from baseline, adjusted for baseline ICH volume.

  24+/-3 hours

Secondary Outcomes (7)

• Major thromboembolic events (myocardial infarction, ischaemic stroke, pulmonary embolism)

  Within 90+/-7 days

• Absolute ICH growth volume by 24±3 hours, adjusted for baseline ICH volume

  24+/-3 hours

• Absolute intraventricular haematoma (IVH) growth volume by 24±3 hours, adjusted for baseline IVH volume

  24+/-3 hours

• modified Rankin Scale (mRS) score of 0-4 at 3 months

  90+/-7 days

• modified Rankin Scale (mRS) score of 0-3 at 3 months

  90+/-7 days

Other Outcomes (2)

• ICH growth

  24+/-3 hours

• modified Rankin Scale (mRS)

  90+/-7 days

Study Arms (2)

Tranexamic Acid

ACTIVE COMPARATOR

Intravenous tranexamic acid 1000 mg in 100 mL 0.9% NaCl over 10 minutes followed by 1000 mg in 500 mL 0.9% NaCl infusion over 8 hours.

Drug: Tranexamic Acid

Placebo

PLACEBO COMPARATOR

Intravenous placebo in 100 mL 0.9% NaCl over 10 minutes followed by 500 mL 0.9% NaCl infusion over 8 hours.

Drug: Placebo

Interventions

Tranexamic Acid DRUG

Tranexamic Acid

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients presenting with an acute ICH
• Contrast extravasation within the haemorrhage, "spot sign", evaluated from the CTA according to three criteria, all of which must be present:
• Serpiginous or spot-like appearance within the margin of a parenchymal haematoma without connection to an outside vessel;
• The density (in Hounsfield units) should be greater than that of the background haematoma (site investigators are not required to document the density); and
• No hyperdensity at the corresponding location on non-contrast CT.
• Age ≥18 years
• Treatment can commence within 1 hour of initial CT and within 4.5 hours of symptom onset (or in patients with unknown time of symptom onset, the time patient was last known to be well)
• Informed consent has been received in accordance to local ethics committee requirements

You may not qualify if:

• Glasgow coma scale (GCS) total score of \<8
• Brainstem ICH
• ICH volume \>70 ml as measured by the ABC/2 method
• 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, tumor, or infection
• Contrast already administered within 24 hours prior to initial CT or contraindication to imaging with CT contrast agents (e.g. known or suspected iodine allergy or significant renal failure)
• Hereditary or acquired haemorrhagic diathesis or coagulation factor deficiency.
• Use of heparin, low-molecular weight heparin, GPIIb/IIIa antagonist, or oral anticoagulation (e.g. warfarin, factor Xa inhibitor, thrombin inhibitor) within the previous 14 days, irrespective of laboratory values
• Pregnancy (women of childbearing potential must be tested)
• Planned surgery for ICH within 24 hours
• Concurrent or planned treatment with haemostatic agents (e.g. prothrombin complex concentrate, vitamin K, fresh frozen plasma, or platelet transfusion)
• Participation in any investigational study in the last 30 days
• Known terminal illness or planned withdrawal of care or comfort care measures.
• 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.

Sponsors & Collaborators

• Neuroscience Trials Australia: lead

Study Sites (11)

Gosford Hospital

Kanwal, New South Wales, 2259, Australia

Location

John Hunter Hospital

Newcastle, New South Wales, 2310, Australia

Location

St. Vincent's Hospital

Sydney, New South Wales, 2010, Australia

Location

Royal Prince Alfred Hospital

Sydney, New South Wales, 2050, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Box Hill Hospital

Box Hill, Victoria, 3128, Australia

Location

Western Hospital

Footscray, Victoria, 3011, Australia

Location

Frankston Hospital

Frankston, Victoria, 3199, Australia

Location

The Royal Melbourne Hospital

Melbourne, Victoria, 3050, Australia

Location

Helsinki University Central Hospital

Helsinki, Finland

Location

Related Publications (4)

• 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.

  PMID: 37870112 DERIVED

• Yogendrakumar V, Wu TY, Churilov L, Tatlisumak T, Strbian D, Jeng JS, Kleinig TJ, Sharma G, Campbell BC, Zhao H, Hsu CY, Meretoja A, Donnan GA, Davis SM, Yassi N. Does tranexamic acid affect intraventricular hemorrhage growth in acute ICH? An analysis of the STOP-AUST trial. Eur Stroke J. 2022 Mar;7(1):15-19. doi: 10.1177/23969873211072402. Epub 2022 Feb 1.

  PMID: 35300248 DERIVED

• Meretoja A, Yassi N, Wu TY, Churilov L, Sibolt G, Jeng JS, Kleinig T, Spratt NJ, Thijs V, Wijeratne T, Cho DY, Shah D, Cloud GC, Phan T, Bladin C, Moey A, Aviv RI, Barras CD, Sharma G, Hsu CY, Ma H, Campbell BCV, Mitchell P, Yan B, Parsons MW, Tiainen M, Curtze S, Strbian D, Tang SC, Harvey J, Levi C, Donnan GA, Davis SM. Tranexamic acid in patients with intracerebral haemorrhage (STOP-AUST): a multicentre, randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2020 Dec;19(12):980-987. doi: 10.1016/S1474-4422(20)30369-0. Epub 2020 Oct 28.

  PMID: 33128912 DERIVED

• Meretoja A, Churilov L, Campbell BC, Aviv RI, Yassi N, Barras C, Mitchell P, Yan B, Nandurkar H, Bladin C, Wijeratne T, Spratt NJ, Jannes J, Sturm J, Rupasinghe J, Zavala J, Lee A, Kleinig T, Markus R, Delcourt C, Mahant N, Parsons MW, Levi C, Anderson CS, Donnan GA, Davis SM. The spot sign and tranexamic acid on preventing ICH growth--AUStralasia Trial (STOP-AUST): protocol of a phase II randomized, placebo-controlled, double-blind, multicenter trial. Int J Stroke. 2014 Jun;9(4):519-24. doi: 10.1111/ijs.12132. Epub 2013 Aug 26.

  PMID: 23981692 DERIVED

MeSH Terms

Conditions

Cerebral Hemorrhage; Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Interventions

Tranexamic Acid

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Atte Meretoja, MD

  The Florey Institute of Neuroscience and Mental Health

  PRINCIPAL INVESTIGATOR

• Geoffrey A Donnan, MD

  The Florey Institute of Neuroscience and Mental Health

  PRINCIPAL INVESTIGATOR

• Stephen M Davis, MD

  Melbourne Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2012
• First Posted: October 8, 2012
• Study Start: December 1, 2012
• Primary Completion: August 14, 2019
• Study Completion: December 1, 2019
• Last Updated: February 26, 2020

Record last verified: 2020-02

Locations

AU (10); FI (1)