Daily Literature Update
Fludrocortisone to treat patients with aneurysmal subarachnoid haemorrhage Protocol for an international phase 3 randomised placebocontrolled multicentre trial
Cohen J, Delaney A, Udy A, et al. Fludrocortisone to treat patients with aneurysmal subarachnoid haemorrhage: Protocol for an international, phase 3, randomised, placebo-controlled, multicentre trial. Crit Care Resusc. 2025 Jun;27(2):100116-. doi: 100116. PMID: 40677678.
Study Type: International phase 3 randomised, placebo-controlled, multicentre trial protocol
Population: Patients with aneurysmal subarachnoid haemorrhage (aSAH)
Intervention: Fludrocortisone (synthetic mineralocorticoid) vs placebo to treat hyponatraemia
Outcomes: Effect on hyponatraemia incidence and clinical outcomes including delayed cerebral ischemia and death/disability
Key Findings
- Hyponatraemia common after aSAH and linked to worse outcomes.
- Fludrocortisone may reduce natriuresis and volume depletion by mitigating cerebral salt wasting syndrome.
- Previous smaller studies showed reduced negative sodium balance and possible lower risk of death/disability with use.
- However, overall current evidence lacks definitive proof for improved clinical outcomes.
- This large phase 3 trial aims to clarify fludrocortisone’s role in treatment of aSAH-associated hyponatraemia and outcomes.
Context & Related Research
- Maeda et al., 1989: RCT showed fludrocortisone reduced negative sodium balance post-aSAH (PMID:2672426)
- Huang et al., 2023: Retrospective analysis found fludrocortisone linked to lower 90-day death/disability risk (PMID:37808869)
- Qureshi et al., 2017: Systematic review found no significant benefits of mineralocorticoids on clinical outcomes (PMID:28987848)
- Kaneko et al., 2016: Meta-analysis reported corticosteroids reduced natriuresis but not neurological outcomes or symptomatic vasospasm (reference.medscape.com, PMID:27173669)
- Current gaps: Need for rigorous large trials to confirm if fludrocortisone improves morbidity and mortality post-aSAH
Strengths & Limitations
| Strengths | Limitations |
|---|---|
| Multicentre, international, phase 3 RCT design | Protocol stage; no outcome data yet |
| Largest trial planned to evaluate mineralocorticoid therapy in aSAH | Potential variability in standard of care across centres |
| Focus on both biochemical and clinically important endpoints | Hyponatraemia mechanistic complexity may limit generalisability |
Clinical Implications & Impact
Pharmacists should monitor sodium and volume status closely in aSAH patients. Fludrocortisone, if proven effective, could be incorporated into protocols to prevent or correct hyponatraemia and reduce complications. Awareness of mineralocorticoid side effects and dosing schedules will be critical. Early intervention targeting cerebral salt wasting may improve patient outcomes and decrease ICU length of stay.
Conclusion
Current evidence highlights fludrocortisone’s potential to mitigate hyponatraemia after aneurysmal subarachnoid haemorrhage; definitive clinical outcome data await results of this phase 3 trial.
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Citations
- Cohen J et al. Crit Care Resusc. 2025 Jun;27(2):100116-. PMID:40677678
- Maeda M et al. Stroke. 1989;20(2):267–274. PMID:2672426
- Huang Y et al. Neurocrit Care. 2023;38(3):450–460. PMID:37808869
- Qureshi AI et al. J Neurosurg. 2017;126(4):1134–1142. PMID:28987848
- Kaneko J et al. Stroke. 2016;47(6):1440–1445. PMID:27173669
