Clinical trial NCT01702636: STOP-AUST: The Spot Sign and Tranexamic Acid On Preventing ICH Growth - AUStralasia Trial
Official title: STOP-AUST: The Spot Sign and Tranexamic Acid On Preventing ICH Growth - AUStralasia Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Neuroscience Trials Australia
Sponsor class: OTHER
First posted: 2012-10-08
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: ICH growth by 24±3 hours as defined by either 33% or 6 ml increase from baseline, adjusted for baseline ICH volume.
timeFrame: 24+/-3 hours
Secondary outcomes:
measure: Major thromboembolic events (myocardial infarction, ischaemic stroke, pulmonary embolism)
timeFrame: Within 90+/-7 days
measure: Absolute ICH growth volume by 24±3 hours, adjusted for baseline ICH volume
timeFrame: 24+/-3 hours
measure: Absolute intraventricular haematoma (IVH) growth volume by 24±3 hours, adjusted for baseline IVH volume
timeFrame: 24+/-3 hours
measure: modified Rankin Scale (mRS) score of 0-4 at 3 months
timeFrame: 90+/-7 days
measure: modified Rankin Scale (mRS) score of 0-3 at 3 months
timeFrame: 90+/-7 days
measure: Categorical shift in mRS at 3 months, subject to the validity of proportional odds assumption
timeFrame: 90+/-7 days
measure: Death due to any cause by 3 months
timeFrame: within 90+/-7 days
Other outcomes:
measure: ICH growth
timeFrame: 24+/-3 hours
measure: modified Rankin Scale (mRS)
timeFrame: 90+/-7 days
Locations:
city: Kanwal
country: Australia
facility: Gosford Hospital
state: New South Wales
city: Newcastle
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: Sydney
country: Australia
facility: St. Vincent's Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Footscray
country: Australia
facility: Western Hospital
state: Victoria
city: Frankston
country: Australia
facility: Frankston Hospital
state: Victoria
city: Melbourne
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
Study officials:
affiliation: The Florey Institute of Neuroscience and Mental Health
name: Atte Meretoja, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Florey Institute of Neuroscience and Mental Health
name: Geoffrey A Donnan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Melbourne Health
name: Stephen M Davis, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.