. 2022 Apr;7(2):158-165.

doi: 10.1136/svn-2021-001070. Epub 2021 Nov 30.

Tranexamic acid for intracerebral haemorrhage within 2 hours of onset: protocol of a phase II randomised placebo-controlled double-blind multicentre trial

Nawaf Yassi^{1

2}, Henry Zhao^{3

4}, Leonid Churilov^{3

5}, Bruce C V Campbell^{3

6}, Teddy Wu⁷, Henry Ma⁸, Andrew Cheung⁹, Timothy Kleinig¹⁰, Helen Brown¹¹, Philip Choi¹², Jiann-Shing Jeng¹³, Annemarei Ranta¹⁴, Hao-Kuang Wang¹⁵, Geoffrey C Cloud^{16

17}, Rohan Grimley¹⁸, Darshan Shah¹⁹, Neil Spratt²⁰, Der-Yang Cho²¹, Karim Mahawish²², Lauren Sanders²³, John Worthington²⁴, Ben Clissold²⁵, Atte Meretoja²⁶, Vignan Yogendrakumar³, Mai Duy Ton²⁷, Duc Phuc Dang²⁸, Nguyen Thai My Phuong²⁹, Huy-Thang Nguyen³⁰, Chung Y Hsu³¹, Gagan Sharma³, Peter J Mitchell³², Bernard Yan³, Mark W Parsons^{3

33}, Christopher Levi²⁰, Geoffrey A Donnan^#³, Stephen M Davis^#³

Affiliations

¹ Department of Medicine and Neurology, Melbourne Brain Centre at The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia nawaf.yassi@unimelb.edu.au.
² Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
³ Department of Medicine and Neurology, Melbourne Brain Centre at The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia.
⁴ Ambulance Victoria, Melbourne, Victoria, Australia.
⁵ Melbourne Medical School, The University of Melbourne, Melbourne, Victoria, Australia.
⁶ Stroke Division, The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.
⁷ Department of Neurology, Christchurch Hospital, Christchurch, New Zealand.
⁸ Department of Neurology, Monash Medical Centre, Monash University, Clayton, Victoria, Australia.
⁹ Department of Interventional Neuroradiology, Liverpool Hospital, Liverpool, New South Wales, Australia.
¹⁰ Department of Neurology, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
¹¹ Department of Neurology, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia.
¹² Department of Neurology, Box Hill Hospital, Eastern Health, Box Hill, Victoria, Australia.
¹³ Stroke Centre and Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
¹⁴ Department of Medicine, Dunedin School of Medicine, University of Otago, Wellington, New Zealand.
¹⁵ Department of Neurosurgery, E-Da Hospital, Yanchao, Kaohsiung, Taiwan.
¹⁶ Department of Neurology, Alfred Hospital, Melbourne, Victoria, Australia.
¹⁷ Department of Clinical Neuroscience, Monash University Central Clinical School, Melbourne, Victoria, Australia.
¹⁸ Department of Medicine, Sunshine Coast University Hospital, Nambour, Queensland, Australia.
¹⁹ Department of Neurology, Gold Coast University Hospital, Southport, Queensland, Australia.
²⁰ Department of Neurology, John Hunter Hospital, The University of Newcastle, Newcastle, New South Wales, Australia.
²¹ Department of Neurosurgery, China Medical University Hospital, Taichung, Taiwan.
²² Department of Internal Medicine, Palmerston North Hospital, Palmerston North, New Zealand.
²³ Department of Neurology, St Vincent's Hospital, Fitzroy, Victoria, Australia.
²⁴ Department of Neurology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
²⁵ Department of Neurology, Geelong Hospital, Geelong, Victoria, Australia.
²⁶ Department of Neurology, Helsinki University Hospital, Helsinki, Finland.
²⁷ Stroke Center, Bach Mai Hospital, Hanoi, Viet Nam.
²⁸ Stroke Department, 103 Military Hospital, Hanoi, Hanoi, Viet Nam.
²⁹ Department of Neurology, Nguyen Tri Phuong Hospital, Ho Chi Minh City, Viet Nam.
³⁰ Department of Cerebrovascular Disease, 115 Hospital, Ho Chi Minh City, Viet Nam.
³¹ Department of Neurology, China Medical University, Taichung, Taiwan.
³² Department of Radiology, Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.
³³ Department of Neurology, Liverpool Hospital, Ingham Institute for Applied Medical Research, University of New South Wales South Western Sydney Clinical School, Sydney, New South Wales, Australia.

^# Contributed equally.

PMID: 34848566
PMCID: PMC9067256
DOI: 10.1136/svn-2021-001070

Tranexamic acid for intracerebral haemorrhage within 2 hours of onset: protocol of a phase II randomised placebo-controlled double-blind multicentre trial

Nawaf Yassi et al. Stroke Vasc Neurol. 2022 Apr.

. 2022 Apr;7(2):158-165.

doi: 10.1136/svn-2021-001070. Epub 2021 Nov 30.

Authors

Affiliations

¹ Department of Medicine and Neurology, Melbourne Brain Centre at The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia nawaf.yassi@unimelb.edu.au.
² Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
³ Department of Medicine and Neurology, Melbourne Brain Centre at The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia.
⁴ Ambulance Victoria, Melbourne, Victoria, Australia.
⁵ Melbourne Medical School, The University of Melbourne, Melbourne, Victoria, Australia.
⁶ Stroke Division, The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.
⁷ Department of Neurology, Christchurch Hospital, Christchurch, New Zealand.
⁸ Department of Neurology, Monash Medical Centre, Monash University, Clayton, Victoria, Australia.
⁹ Department of Interventional Neuroradiology, Liverpool Hospital, Liverpool, New South Wales, Australia.
¹⁰ Department of Neurology, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
¹¹ Department of Neurology, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia.
¹² Department of Neurology, Box Hill Hospital, Eastern Health, Box Hill, Victoria, Australia.
¹³ Stroke Centre and Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
¹⁴ Department of Medicine, Dunedin School of Medicine, University of Otago, Wellington, New Zealand.
¹⁵ Department of Neurosurgery, E-Da Hospital, Yanchao, Kaohsiung, Taiwan.
¹⁶ Department of Neurology, Alfred Hospital, Melbourne, Victoria, Australia.
¹⁷ Department of Clinical Neuroscience, Monash University Central Clinical School, Melbourne, Victoria, Australia.
¹⁸ Department of Medicine, Sunshine Coast University Hospital, Nambour, Queensland, Australia.
¹⁹ Department of Neurology, Gold Coast University Hospital, Southport, Queensland, Australia.
²⁰ Department of Neurology, John Hunter Hospital, The University of Newcastle, Newcastle, New South Wales, Australia.
²¹ Department of Neurosurgery, China Medical University Hospital, Taichung, Taiwan.
²² Department of Internal Medicine, Palmerston North Hospital, Palmerston North, New Zealand.
²³ Department of Neurology, St Vincent's Hospital, Fitzroy, Victoria, Australia.
²⁴ Department of Neurology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
²⁵ Department of Neurology, Geelong Hospital, Geelong, Victoria, Australia.
²⁶ Department of Neurology, Helsinki University Hospital, Helsinki, Finland.
²⁷ Stroke Center, Bach Mai Hospital, Hanoi, Viet Nam.
²⁸ Stroke Department, 103 Military Hospital, Hanoi, Hanoi, Viet Nam.
²⁹ Department of Neurology, Nguyen Tri Phuong Hospital, Ho Chi Minh City, Viet Nam.
³⁰ Department of Cerebrovascular Disease, 115 Hospital, Ho Chi Minh City, Viet Nam.
³¹ Department of Neurology, China Medical University, Taichung, Taiwan.
³² Department of Radiology, Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.
³³ Department of Neurology, Liverpool Hospital, Ingham Institute for Applied Medical Research, University of New South Wales South Western Sydney Clinical School, Sydney, New South Wales, Australia.

^# Contributed equally.

PMID: 34848566
PMCID: PMC9067256
DOI: 10.1136/svn-2021-001070

Abstract

Rationale: Haematoma growth is common early after intracerebral haemorrhage (ICH), and is a key determinant of outcome. Tranexamic acid, a widely available antifibrinolytic agent with an excellent safety profile, may reduce haematoma growth.

Methods and design: Stopping intracerebral haemorrhage with tranexamic acid for hyperacute onset presentation including mobile stroke units (STOP-MSU) is a phase II double-blind, randomised, placebo-controlled, multicentre, international investigator-led clinical trial, conducted within the estimand statistical framework.

Hypothesis: In patients with spontaneous ICH, treatment with tranexamic acid within 2 hours of onset will reduce haematoma expansion compared with placebo.

Sample size estimates: A sample size of 180 patients (90 in each arm) would be required to detect an absolute difference in the primary outcome of 20% (placebo 39% vs treatment 19%) under a two-tailed significance level of 0.05. An adaptive sample size re-estimation based on the outcomes of 144 patients will allow a possible increase to a prespecified maximum of 326 patients.

Intervention: Participants will receive 1 g intravenous tranexamic acid over 10 min, followed by 1 g intravenous tranexamic acid over 8 hours; or matching placebo.

Primary efficacy measure: The primary efficacy measure is the proportion of patients with haematoma growth by 24±6 hours, defined as either ≥33% relative increase or ≥6 mL absolute increase in haematoma volume between baseline and follow-up CT scan.

Discussion: We describe the rationale and protocol of STOP-MSU, a phase II trial of tranexamic acid in patients with ICH within 2 hours from onset, based in participating mobile stroke units and emergency departments.

Keywords: CT; hemorrhage; stroke.

PubMed Disclaimer

Conflict of interest statement

Competing interests: Henry Zhao has received grant funding from the Medical Research Future Fund (Commonwealth Government of Australia). Leonid Churilov is co-chairperson of the Australasian Stroke Trials Network (unpaid). Andrew Cheung has received honoraria for lectures/presentations from Medtronic and Stryker and support for attending meetings and/or travel from Stryker. Rohan Grimley is a member of the Clinical Council, Stroke Foundation (Australia). Chung Hsu has received grants from the Ministry of Health and Welfare in Taiwan. Peter Mitchell has received institutional research grants from Stryker and Medtronic, travel support for attendance of international conferences and honoraria for speaking at symposia from Stryker, and is an executive member and immediate past president of the Australian and New Zealand Society of Neuroradiology (ANZSNR).

Figures

**Figure 1**
Haematoma growth occurring between baseline (A, C) CT and follow-up CT (B, D) in a patient with a right basal ganglia haemorrhage. Panel C and D reflect the region of interest planimetric analysis used to measure haematoma volume (intraventricular segment measured separately).

**Figure 2**
Key trial timepoints and activities. ICH, intracerebral haemorrhage; mRS, Modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; TXA, tranexamic acid.

See this image and copyright information in PMC

References

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Tranexamic acid for intracerebral haemorrhage within 2 hours of onset: protocol of a phase II randomised placebo-controlled double-blind multicentre trial

Affiliations

Tranexamic acid for intracerebral haemorrhage within 2 hours of onset: protocol of a phase II randomised placebo-controlled double-blind multicentre trial

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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LinkOut - more resources

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