Does tranexamic acid lead to changes in MRI measures of brain tissue health in patients with spontaneous intracerebral haemorrhage? Protocol for a MRI substudy nested within the double-blind randomised controlled TICH-2 trial

Rob A. Dineen, Stefan Pszczolkowski, Katie Flaherty, Zhe Kang Law, Paul S. Morgan, Ian Roberts, David J. Werring, Rustam Al Shahi Salman, Tim England, Philip M. Bath, Nikola Sprigg

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Objectives To test whether administration of the antifibrinolytic drug tranexamic acid (TXA) in patients with spontaneous intracerebral haemorrhage (SICH) leads to increased prevalence of diffusion-weighted MRI-defined hyperintense ischaemic lesions (primary hypothesis) or reduced perihaematomal oedema volume, perihaematomal diffusion restriction and residual MRI-defined SICH-related tissue damage (secondary hypotheses). Design MRI substudy nested within the double-blind randomised controlled Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage (TICH)-2 trial (ISRCTN93732214). Setting International multicentre hospital-based study. Participants Eligible adults consented and randomised in the TICH-2 trial who were also able to undergo MRI scanning. To address the primary hypothesis, a sample size of n=280 will allow detection of a 10% relative increase in prevalence of diffusion-weighted imaging (DWI) hyperintense lesions in the TXA group with 5% significance, 80% power and 5% imaging data rejection. Interventions TICH-2 MRI substudy participants will undergo MRI scanning using a standardised protocol at day ∼5 and day ∼90 after randomisation. Clinical assessments, randomisation to TXA or placebo and participant follow-up will be performed as per the TICH-2 trial protocol. Conclusion The TICH-2 MRI substudy will test whether TXA increases the incidence of new DWI-defined ischaemic lesions or reduces perihaematomal oedema or final ICH lesion volume in the context of SICH. Ethics and dissemination The TICH-2 trial obtained ethical approval from East Midlands - Nottingham 2 Research Ethics Committee (12/EM/0369) and an amendment to allow the TICH-2 MRI sub study was approved in April 2015 (amendment number SA02/15). All findings will be published in peer-reviewed journals. The primary outcome results will also be presented at a relevant scientific meeting. Trial registration number ISRCTN93732214; Pre-results.

Original languageEnglish
Article numbere019930
JournalBMJ Open
Volume8
Issue number2
DOIs
Publication statusPublished - 1 Feb 2018

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Tranexamic Acid
Cerebral Hemorrhage
Health
Brain
Random Allocation
Edema
Antifibrinolytic Agents
Diffusion Magnetic Resonance Imaging
Research Ethics Committees
Clinical Protocols
Ethics
Sample Size
Placebos
Incidence
Pharmaceutical Preparations

Keywords

  • diffusion weighted imaging
  • hyperacute primary intracerebral haemorrhage
  • magnetic resonance imaging
  • perihaematomal oedema
  • tranexamic acid

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Does tranexamic acid lead to changes in MRI measures of brain tissue health in patients with spontaneous intracerebral haemorrhage? Protocol for a MRI substudy nested within the double-blind randomised controlled TICH-2 trial. / Dineen, Rob A.; Pszczolkowski, Stefan; Flaherty, Katie; Law, Zhe Kang; Morgan, Paul S.; Roberts, Ian; Werring, David J.; Salman, Rustam Al Shahi; England, Tim; Bath, Philip M.; Sprigg, Nikola.

In: BMJ Open, Vol. 8, No. 2, e019930, 01.02.2018.

Research output: Contribution to journalArticle

Dineen, Rob A. ; Pszczolkowski, Stefan ; Flaherty, Katie ; Law, Zhe Kang ; Morgan, Paul S. ; Roberts, Ian ; Werring, David J. ; Salman, Rustam Al Shahi ; England, Tim ; Bath, Philip M. ; Sprigg, Nikola. / Does tranexamic acid lead to changes in MRI measures of brain tissue health in patients with spontaneous intracerebral haemorrhage? Protocol for a MRI substudy nested within the double-blind randomised controlled TICH-2 trial. In: BMJ Open. 2018 ; Vol. 8, No. 2.
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abstract = "Objectives To test whether administration of the antifibrinolytic drug tranexamic acid (TXA) in patients with spontaneous intracerebral haemorrhage (SICH) leads to increased prevalence of diffusion-weighted MRI-defined hyperintense ischaemic lesions (primary hypothesis) or reduced perihaematomal oedema volume, perihaematomal diffusion restriction and residual MRI-defined SICH-related tissue damage (secondary hypotheses). Design MRI substudy nested within the double-blind randomised controlled Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage (TICH)-2 trial (ISRCTN93732214). Setting International multicentre hospital-based study. Participants Eligible adults consented and randomised in the TICH-2 trial who were also able to undergo MRI scanning. To address the primary hypothesis, a sample size of n=280 will allow detection of a 10{\%} relative increase in prevalence of diffusion-weighted imaging (DWI) hyperintense lesions in the TXA group with 5{\%} significance, 80{\%} power and 5{\%} imaging data rejection. Interventions TICH-2 MRI substudy participants will undergo MRI scanning using a standardised protocol at day ∼5 and day ∼90 after randomisation. Clinical assessments, randomisation to TXA or placebo and participant follow-up will be performed as per the TICH-2 trial protocol. Conclusion The TICH-2 MRI substudy will test whether TXA increases the incidence of new DWI-defined ischaemic lesions or reduces perihaematomal oedema or final ICH lesion volume in the context of SICH. Ethics and dissemination The TICH-2 trial obtained ethical approval from East Midlands - Nottingham 2 Research Ethics Committee (12/EM/0369) and an amendment to allow the TICH-2 MRI sub study was approved in April 2015 (amendment number SA02/15). All findings will be published in peer-reviewed journals. The primary outcome results will also be presented at a relevant scientific meeting. Trial registration number ISRCTN93732214; Pre-results.",
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AU - Flaherty, Katie

AU - Law, Zhe Kang

AU - Morgan, Paul S.

AU - Roberts, Ian

AU - Werring, David J.

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