HAMLET Trial: Hemicraniectomy for Space-Occupying Hemispheric Infarction
In patients aged 18-60 with space-occupying hemispheric infarction randomized within 96 hours, does decompressive surgery reduce death and improve functional independence compared with best medical treatment?
Hofmeijer et al. (Lancet Neurol 2009) · doi:10.1016/S1474-4422(09)70047-X · 64 patients
Population
Included
- Age 18-60 years
- Space-occupying hemispheric infarction with declining consciousness
- Randomization within 4 days (96 hours) of symptom onset
- CT or MRI confirmation of malignant MCA infarction
Demographics
- Age 18–60 years
Clinical
- Diagnosis of acute ischaemic stroke in the territory of the middle cerebral artery, with onset within 96 h of the start of the trial treatment
- Score on the NIHSS of >=16 for right-sided lesions or >=21 for left-sided lesions
- Gradual decrease in consciousness to a score of <=13 on the Glasgow coma scale for right-sided lesions or an eye and motor score of <=9 for left-sided lesions
Imaging
- Ischaemic changes on CT that affect two-thirds or more of the territory of the middle cerebral artery and the formation of space-occupying oedema; displacement of midline structures on CT was not required
Timing / consent
- Able to start trial treatment within 3 h of randomisation
- Written, informed consent given by a legal representative of the patient
Excluded
- Age greater than 60 years
- Pre-existing severe disability
- Bilateral infarcts or posterior fossa involvement
- Terminal illness or major organ failure
- Hemorrhagic transformation before randomization
Imaging / lesion
- Ischaemic stroke of the whole cerebral hemisphere (anterior, middle, and posterior cerebral artery territories)
Neurological / clinical
- Decrease in consciousness partially because of causes other than the formation of oedema, such as metabolic disturbances or medication
- Both pupils fixed and dilated
Treatment / bleeding
- Alteplase in the 12 h before randomisation
- Known systemic bleeding disorder
Pre-stroke function
- Prestroke score on the modified Rankin scale of greater than 1 or less than 95 on the Barthel index
Other
- Life expectancy is less than 3 years
- Other serious illness that might confound treatment assessment
Source: Hofmeijer et al., Lancet Neurology 2009· Retrieved 2026-06-09
Mortality Outcome — 1-Year Survival
64 patients; surgical decompression vs best medical treatment (enrollment up to 96 hours)
1-Year Survival
Primary endpoint mRS 0-3 at 1 year was neutral overall. Functional benefit was concentrated in patients operated within 48 hours; patients enrolled after 48 hours diluted the functional treatment effect.
Study Arms
- Agent
- Decompressive hemicraniectomy
- Route
- Surgical
- Duration
- Treatment started within 3 h of randomisation; randomisation within 96 h of stroke onset
- Co-interventions
- Most patients admitted to an ICU after craniectomy. Shared ICU recommendations: osmotherapy with mannitol or glycerol to serum osmolality 315–320 mOsm; intubation/ventilation if GCS <=8 or airway compromise; hyperventilation as rescue only (target pCO2 28–32 mm Hg); invasive ICP monitoring; sedation with propofol if needed; BP treatment above 220/120 mm Hg; head elevation to 30 degrees; normothermia, normoglycaemia, normovolaemia.
Removal of a bone flap of at least 12 cm diameter, including parts of the frontal, parietal, temporal, and occipital squama; more temporal bone removed if needed to assess the floor of the middle cerebral fossa. Dura opened and an augmented dural patch inserted. Infarcted brain tissue not resected. An ICP sensor could be left in situ. Cranioplasty after at least 6 weeks with the stored bone flap or acrylate.
- Agent
- Conservative medical management
- Route
- Intensive care unit or stroke unit
- Co-interventions
- ICU recommendations: osmotherapy (serum osmolality 315–320 mOsm), intubation/ventilation if GCS <=8, hyperventilation as rescue only (pCO2 28–32 mm Hg), ICP monitoring, sedation, BP control above 220/120 mm Hg, head elevation 30 degrees, normothermia/normoglycaemia/normovolaemia. On a stroke unit: osmotherapy, head elevation, normothermia/normoglycaemia/normovolaemia.
Best medical treatment at the discretion of the treating physician, on an ICU or stroke unit; no decompressive surgery. Drugs to prevent oedema given at the physician's discretion.
Trial Design
Type
- Multicenter open randomized trial
- Surgical decompression vs best medical treatment
- Patients randomized within 4 days of stroke onset
- Primary endpoint based on mRS 0-3 at 1 year
Timeline
Netherlands, 2002-2007
N
64
Enrollment
64 patients at multiple Dutch centers. Multicenter open randomized trial. Patients aged 18-60 randomized within 4 days (96 hours) of stroke onset. Primary endpoint mRS 0-3 at 1 year. Published Lancet Neurol 2009.
Bedside Pearl
HAMLET's most important teaching is the 48-hour window. Mortality benefit from hemicraniectomy is seen across the enrollment window (up to 96 hours), but functional benefit (and the strongest mortality benefit) is concentrated in patients operated within 48 hours of onset. For patients presenting after 48 hours and before 96 hours, surgery may still reduce death but does not reliably improve functional independence. Tell families explicitly: operating after 48 hours means accepting a higher chance the patient survives with severe disability. The pooled analysis (DECIMAL, DESTINY, HAMLET within 48 hours) is the definitive evidence base for counseling when operating within the 48-hour window.
See also
Trial lineage
Hemicraniectomy for malignant MCA infarction
Three near-simultaneous European RCTs (DECIMAL, DESTINY, HAMLET) established that decompressive hemicraniectomy reduces mortality in younger patients with space-occupying MCA infarction. The pooled analysis underpins the AHA/ASA Class I recommendation in patients up to 60 years. DESTINY II later extended the question to patients over 60, where survival is preserved but most survivors have moderate-to-severe disability.
- 2007DECIMAL TrialNEUTRAL
- 2007DESTINY TrialNEUTRAL
- 2009HAMLET Trial· this pageNEUTRAL
- 2014DESTINY II TrialPOSITIVE