Mannitol for cerebral oedema after acute intracerebral haemorrhage (MACE-ICH): protocol for a prospective, randomised, open-label, blinded-endpoint phase IIb trial
Background Acute intracerebral haemorrhage (ICH) is devastating with a 1 month mortality rate of ~40%. Cerebral oedema can complicate acute ICH and is associated with poor outcome. In patients with large ICH, the accompanying swelling increases mass effect and causes brain herniation. Mannitol, an o...
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BMJ Publishing Group
2025-07-01
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| author | Jesse Dawson David J Werring Nikola Sprigg Christine Roffe Zhe Kang Law Kailash Krishnan Philip Bath Rob A Dineen Diane Havard Timothy J England Mary Joan Macleod Stefan Pszczolkowski Jennifer Craig Amanda Buck David W Hewson Lisa Woodhouse Fergus Doubal Emma Grace Keenan Wells |
| author_facet | Jesse Dawson David J Werring Nikola Sprigg Christine Roffe Zhe Kang Law Kailash Krishnan Philip Bath Rob A Dineen Diane Havard Timothy J England Mary Joan Macleod Stefan Pszczolkowski Jennifer Craig Amanda Buck David W Hewson Lisa Woodhouse Fergus Doubal Emma Grace Keenan Wells |
| author_sort | Jesse Dawson |
| collection | DOAJ |
| description | Background Acute intracerebral haemorrhage (ICH) is devastating with a 1 month mortality rate of ~40%. Cerebral oedema can complicate acute ICH and is associated with poor outcome. In patients with large ICH, the accompanying swelling increases mass effect and causes brain herniation. Mannitol, an osmotic diuretic, is used to treat cerebral oedema after traumatic brain injury, but its safety and efficacy in ICH is unclear. We aim to assess the feasibility of a phase II randomised, controlled trial of mannitol in patients with ICH with, or at risk of, cerebral oedema to inform a definitive trial.Methods The mannitol for cerebral oedema after acute intracerebral haemorrhage trial (MACE-ICH) aims to include 45 ICH participants from 10 UK sites with estimated largest diameter of haematoma volume >2 cm, presenting within 72 hours of onset with, or at risk of, cerebral oedema (limited Glasgow Coma Scale (GCS)<9, including motor and visual components only, and National Institutes of Health Stroke Scale>8) with or without mass effect. Participants will be randomised (1:1:1) to 1 g/kg 10% single-dose intravenous mannitol, 1 g/kg 10% mannitol followed by a second dose at 24 hours, or standard care alone. Outcome assessors will be masked to treatment allocation. Feasibility outcomes include proportion of patients approached being randomised, participants receiving allocated treatment, recruitment rate, treatment adherence and follow-up. Secondary outcomes include serum electrolytes and osmolality at days 1–2; change in ICH and oedema volume at day 5; number of participants who developed urinary tract infection, GCS and National Institutes of Health Stroke Scale at day 5±2; length of hospital stay, discharge destination and death up to day 28; death and death or dependency by day 180 and disability (Barthel Index), quality of life (EuroQol, 5-D) and cognition (telephone mini-mental state examination) at day 180.Ethics and dissemination MACE-ICH received ethics approval from the East Midlands-Leicester Central research ethics committee (22/EM/0242). The trial is funded by a National Institute for Health and Care Research RfPB grant (203080). The results will be published in an academic journal and disseminated through academic conferences and patient support groups. Reporting will be in line with Consolidated Standards of Reporting Trials recommendations.Trial registration numbers ISRCTN15383301; EUDRACT 2022-000283-22. |
| format | Article |
| id | doaj-art-cadf38e826ff470785814d056273d184 |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMJ Publishing Group |
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| series | BMJ Open |
| spelling | doaj-art-cadf38e826ff470785814d056273d1842025-08-20T03:58:41ZengBMJ Publishing GroupBMJ Open2044-60552025-07-0115710.1136/bmjopen-2025-103776Mannitol for cerebral oedema after acute intracerebral haemorrhage (MACE-ICH): protocol for a prospective, randomised, open-label, blinded-endpoint phase IIb trialJesse Dawson0David J Werring1Nikola Sprigg2Christine Roffe3Zhe Kang Law4Kailash Krishnan5Philip Bath6Rob A Dineen7Diane Havard8Timothy J England9Mary Joan Macleod10Stefan Pszczolkowski11Jennifer Craig12Amanda Buck13David W Hewson14Lisa Woodhouse15Fergus Doubal16Emma Grace17Keenan Wells18Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UKUCL Institute of Neurology, London, UKUniversity of Nottingham, Nottingham, UKInstitute for Science and Technology in Medicine, Keele University, Keele, UKDepartment of Medicine, National University of Malaysia, Kuala Lumpur, MalaysiaUniversity of Nottingham, Nottingham, UKUniversity of Nottingham, Nottingham, UKRadiological Sciences, Academic Unit of Mental Health and Clinical Neuroscience, University of Nottingham, Nottingham, UK6Division of Clinical Neuroscience, University of Nottingham, Nottingham, UKUniversity of Nottingham, Derby, UKUniversity of Aberdeen Division of Applied Medicine, Aberdeen, UKUniversity of Nottingham, Nottingham, UKMental Health & Clinical Neuroscience, University of Nottingham, Nottingham, UKUniversity of Nottingham, Nottingham, UKUniversity of Nottingham, Nottingham, UKStroke Trials Unit, Mental Health & Clinical Neurosciences, University of Nottingham, Nottingham, UKThe University of Edinburgh, Edinburgh, UKDepartment of Acute Medicine, Nottingham University Hospitals NHS Trust, Nottingham, UKUniversity of Nottingham, Nottingham, UKBackground Acute intracerebral haemorrhage (ICH) is devastating with a 1 month mortality rate of ~40%. Cerebral oedema can complicate acute ICH and is associated with poor outcome. In patients with large ICH, the accompanying swelling increases mass effect and causes brain herniation. Mannitol, an osmotic diuretic, is used to treat cerebral oedema after traumatic brain injury, but its safety and efficacy in ICH is unclear. We aim to assess the feasibility of a phase II randomised, controlled trial of mannitol in patients with ICH with, or at risk of, cerebral oedema to inform a definitive trial.Methods The mannitol for cerebral oedema after acute intracerebral haemorrhage trial (MACE-ICH) aims to include 45 ICH participants from 10 UK sites with estimated largest diameter of haematoma volume >2 cm, presenting within 72 hours of onset with, or at risk of, cerebral oedema (limited Glasgow Coma Scale (GCS)<9, including motor and visual components only, and National Institutes of Health Stroke Scale>8) with or without mass effect. Participants will be randomised (1:1:1) to 1 g/kg 10% single-dose intravenous mannitol, 1 g/kg 10% mannitol followed by a second dose at 24 hours, or standard care alone. Outcome assessors will be masked to treatment allocation. Feasibility outcomes include proportion of patients approached being randomised, participants receiving allocated treatment, recruitment rate, treatment adherence and follow-up. Secondary outcomes include serum electrolytes and osmolality at days 1–2; change in ICH and oedema volume at day 5; number of participants who developed urinary tract infection, GCS and National Institutes of Health Stroke Scale at day 5±2; length of hospital stay, discharge destination and death up to day 28; death and death or dependency by day 180 and disability (Barthel Index), quality of life (EuroQol, 5-D) and cognition (telephone mini-mental state examination) at day 180.Ethics and dissemination MACE-ICH received ethics approval from the East Midlands-Leicester Central research ethics committee (22/EM/0242). The trial is funded by a National Institute for Health and Care Research RfPB grant (203080). The results will be published in an academic journal and disseminated through academic conferences and patient support groups. Reporting will be in line with Consolidated Standards of Reporting Trials recommendations.Trial registration numbers ISRCTN15383301; EUDRACT 2022-000283-22.https://bmjopen.bmj.com/content/15/7/e103776.full |
| spellingShingle | Jesse Dawson David J Werring Nikola Sprigg Christine Roffe Zhe Kang Law Kailash Krishnan Philip Bath Rob A Dineen Diane Havard Timothy J England Mary Joan Macleod Stefan Pszczolkowski Jennifer Craig Amanda Buck David W Hewson Lisa Woodhouse Fergus Doubal Emma Grace Keenan Wells Mannitol for cerebral oedema after acute intracerebral haemorrhage (MACE-ICH): protocol for a prospective, randomised, open-label, blinded-endpoint phase IIb trial BMJ Open |
| title | Mannitol for cerebral oedema after acute intracerebral haemorrhage (MACE-ICH): protocol for a prospective, randomised, open-label, blinded-endpoint phase IIb trial |
| title_full | Mannitol for cerebral oedema after acute intracerebral haemorrhage (MACE-ICH): protocol for a prospective, randomised, open-label, blinded-endpoint phase IIb trial |
| title_fullStr | Mannitol for cerebral oedema after acute intracerebral haemorrhage (MACE-ICH): protocol for a prospective, randomised, open-label, blinded-endpoint phase IIb trial |
| title_full_unstemmed | Mannitol for cerebral oedema after acute intracerebral haemorrhage (MACE-ICH): protocol for a prospective, randomised, open-label, blinded-endpoint phase IIb trial |
| title_short | Mannitol for cerebral oedema after acute intracerebral haemorrhage (MACE-ICH): protocol for a prospective, randomised, open-label, blinded-endpoint phase IIb trial |
| title_sort | mannitol for cerebral oedema after acute intracerebral haemorrhage mace ich protocol for a prospective randomised open label blinded endpoint phase iib trial |
| url | https://bmjopen.bmj.com/content/15/7/e103776.full |
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