Abstract
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.
| Original language | English |
|---|---|
| Article number | e103776 |
| Number of pages | 8 |
| Journal | BMJ Open |
| Volume | 15 |
| Issue number | 7 |
| Early online date | 28 Jul 2025 |
| DOIs | |
| Publication status | Published - 28 Jul 2025 |
Bibliographical note
We would like to thank the participants and their caregivers who are participating in MACE-ICH. We also thank the DMC, research collaborators and investigators at the participating centres for their contribution to this trial. PB is Stroke Association Professor of Stroke Medicine and an emeritus NIHR Senior Investigator. This manuscript presents independent research funded by the National Institute for Health Research (NIHR) under the Research for Patient Benefit Programme (award ID: NIHR 203080). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. The sponsor of this trial and funders have no role in trial design, trial management, data collection, analysis and interpretation of the data, writing of the report and the decision to submit the manuscript for publication. The National University of Malaysia (GP-K019817) is acknowledged for awarding Zhe Kang Law with a research grant and supporting this publication.Funding
This manuscript presents independent research funded by the National Institute for Health Research (NIHR) under the Research for Patient Benefit Programme (award ID: NIHR 203080). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. The sponsor of this trial and funders have no role in trial design, trial management, data collection, analysis and interpretation of the data, writing of the report and the decision to submit the manuscript for publication. The National University of Malaysia (GP-K019817) is acknowledged for awarding Zhe Kang Law with a research grant and supporting this publication.
| Funders | Funder number |
|---|---|
| National Institute for Health and Care Research | ISRCTN15383301, NIHR 203080 |
| Universiti Kebangsaan Malaysia | GP-K019817 |
Keywords
- Clinical trials
- Intracerebral Hemorrhage
- STROKE MEDICINE