Baseline characteristics of patients recruited to the mannitol for cerebral oedema after acute intracerebral haemorrhage (MACE-ICH) trial

Abstract

Background

Mannitol, an osmotic diuretic and free radical scavenger might decrease cerebral oedema after acute intracerebral haemorrhage.

Aims

The Mannitol for cerebral oedema after acute intracerebral haemorrhage trial is testing the feasibility of performing a phase II trial to define the optimal approach for a phase III trial of testing mannitol in patients with cerebral oedema or at risk of it to improve outcome.

Methods

MACE-ICH is a multicentre, prospective, randomised, open-label, blinded-endpoint outcome assessment trial. Participants presenting within 72 h of ictus were randomised to one of three groups: 1:1 g/kg 10 % single dose mannitol infusion at 10 ml/min, in addition to standard care; 1 g/kg 10 % mannitol at 10 ml/min followed by a second dose 1 g/kg repeated 24 h later (providing serum osmolality <320 mOsm/Kg and sodium<160 mmol/L), in addition to standard care or standard care alone. The trial was registered prospectively: ISRCTN15383301.

Results

46 (of planned 45) participants were recruited from 8 sites between February 2024-April 2025. Baseline characteristics: mean age 74.7 years (standard deviation 12.0); male 69 %; onset-to-randomisation 22.9 h; severity (National Institutes of Health Stroke Scale) 12.1 (8.3); blood pressure 155.3 (29.0)/78.9 (16.5) mmHg. Haematoma characteristics: lobar 58 %, mass effect 58.7 %, midline shift (34.8 %). The mean maximum haemorrhage diameter was 4.3 cm.

Conclusion

MACE-ICH successfully enroled patients with cerebral oedema after acute intracerebral haemorrhage to assess the feasibility and safety of intravenous mannitol. The trial is novel with a dose-comparative approach with assessment of single and repeated mannitol dosing regimens, addressing an important gap in clinical practice.