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

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

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.

Study Overview

• Status: Completed
• Conditions: Stroke; Intracerebral Haemorrhage
• Intervention / Treatment: Drug: Placebo; Drug: Tranexamic Acid

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kanwal, New South Wales, Australia, 2259
      • Gosford Hospital
    • Newcastle, New South Wales, Australia, 2310
      • John Hunter Hospital
    • Sydney, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • Sydney, New South Wales, Australia, 2010
      • St. Vincent's Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital
    • Footscray, Victoria, Australia, 3011
      • Western Hospital
    • Frankston, Victoria, Australia, 3199
      • Frankston Hospital
    • Melbourne, Victoria, Australia, 3050
      • The Royal Melbourne Hospital
• Finland
  • Helsinki, Finland
    • Helsinki University Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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:

  1. Serpiginous or spot-like appearance within the margin of a parenchymal haematoma without connection to an outside vessel;
  2. The density (in Hounsfield units) should be greater than that of the background haematoma (site investigators are not required to document the density); and
  3. 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

Exclusion Criteria:

• 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)
• 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.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tranexamic Acid; 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 Comparator: Placebo; Intravenous placebo in 100 mL 0.9% NaCl over 10 minutes followed by 500 mL 0.9% NaCl infusion over 8 hours.	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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
Categorical shift in mRS at 3 months, subject to the validity of proportional odds assumption	90+/-7 days
Death due to any cause by 3 months	within 90+/-7 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICH growth	Exploratory analyses will be run with adjustments for baseline variables such as age, Glasgow Coma Scale (GCS), presence of IVH, and ICH location, and in the following subgroups: onset-to-treatment time (<3 vs. >3 hours); baseline ICH volume (<30 vs. >30 ml); anatomical location (deep, lobar, or cerebellar); IVH (absent vs. present); GCS (>12 vs. 8-12) and age (<70 vs. >70). These analyses will be hypothesis generating, as the trial is not powered for them.	24+/-3 hours
modified Rankin Scale (mRS)	Exploratory analyses will be run with adjustments for baseline variables such as age, Glasgow Coma Scale (GCS), presence of IVH, and ICH location, and in the following subgroups: onset-to-treatment time (<3 vs. >3 hours); baseline ICH volume (<30 vs. >30 ml); anatomical location (deep, lobar, or cerebellar); IVH (absent vs. present); GCS (>12 vs. 8-12) and age (<70 vs. >70). These analyses will be hypothesis generating, as the trial is not powered for them.	90+/-7 days

Collaborators and Investigators

• Sponsor: Neuroscience Trials Australia
• Investigators: Principal Investigator: 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

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2012
• Primary Completion (Actual): August 14, 2019
• Study Completion (Actual): December 1, 2019

Study Registration Dates

• First Submitted: October 3, 2012
• First Submitted That Met QC Criteria: October 4, 2012
• First Posted (Estimate): October 8, 2012

Study Record Updates

• Last Update Posted (Actual): February 26, 2020
• Last Update Submitted That Met QC Criteria: February 24, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Stroke; Vascular Diseases; Cardiovascular Diseases; Nervous System Diseases; ICH; Central Nervous System Diseases; Tomography, X-Ray Computed; Pharmacologic Actions; Contrast Media; Brain Diseases; Therapeutic Uses; Tranexamic Acid; Angiography; Cerebrovascular Disorders; Intracerebral Hemorrhage; Cardiovascular Agents; Hemostatics; Antifibrinolytic Agents; Hematologic Agents; Fibrin Modulating Agents; Cerebral Angiography
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Cerebral Hemorrhage; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: NTA1201