Cerebral Edema, Stroke, Ischemic
Conditions
Keywords
Acute Ischemic Stroke, Endovascular Thrombectomy, Cerebral Edema, Hemicraniectomy
Brief summary
Early Decompressive Hemicraniectomy for High-Risk Large Ischemic Core Stroke Post-EVTAcute Ischemic Stroke (AIS), particularly Anterior Circulation Large Vessel Occlusion (LVO), is a major cause of global disability and death. While endovascular thrombectomy (EVT) is the standard first-line treatment for LVO, outcomes remain poor in patients with large ischemic cores (ASPECTS ≤5). Despite high recanalization rates (\>90%), only 14-30% achieve functional independence (mRS 0-2) at 90 days, with 33-50% dead or severely disabled (mRS 5-6). Outcomes worsen dramatically with larger core volumes (e.g., only 4.4% functional independence with cores ≥150mL in SELECT2).A critical complication is Malignant Cerebral Edema (MCE), affecting \ 50% of large-core patients post-EVT. MCE triggers a vicious cycle of rising intracranial pressure, reduced perfusion, and brain herniation. It drastically worsens prognosis: functional independence rates plummet (13.3% vs 51.2% without MCE), mortality significantly increases (OR=7.96, p=0.001), and functional outcomes deteriorate (OR=7.83, p=0.008). Strong predictors include low ASPECTS (\<7) and large infarct volume.Decompressive Hemicraniectomy (DHC) is a life-saving intervention for MCE. Landmark trials (DESTINY, DECIMAL, HAMLET) and their meta-analysis show DHC within 24 hours in patients aged 18-60 significantly increases 12-month survival (78% vs 29%, ARR 50%) and rates of ambulatory independence (mRS ≤3: 43% vs 21%, ARR 23%). DESTINY II confirmed benefit in patients \>60, improving functional outcomes (mRS 0-4: 38% vs 16%). Guidelines endorse DHC for large infarcts with deterioration.However, significant challenges persist: DHC is Underutilized: Despite evidence, clinical adoption remains low.Rescue DHC Fails to Improve Outcomes in Post-EVT MCE: Studies report poor functional outcomes (only 20% mRS 0-2) and high mortality (48.6%) with standard medical therapy (SMT) plus rescue DHC after MCE develops. Retrospective data confirms worse outcomes in these patients (mRS 0-2: 16.4% vs 50%; mortality: 46.5% vs 20%) compared to those without MCE. Crucially, rescue DHC itself fails to improve prognosis once MCE is established (mRS 5-6: 64% vs 57.7%; mortality: 48% vs 46.2%).High-Risk Identification: Patients defined as high-risk for MCE (ASPECTS 3-5 + NIHSS≥30 or ASPECTS≤2) have significantly worse 90-day outcomes (mRS 0-2: 23.2% vs 44.6%; mortality: 44% vs 22.7%).Timing is Critical: Rescue DHC is often performed too late, after irreversible neurological damage occurs. Early/Prophylactic DHC, performed before significant edema and herniation develop, offers a potential pathophysiological advantage. It may:Improve cerebral perfusion pressure earlier. Reduce mass effect and edema progression. Mitigate secondary injury (e.g., reduce oxygen-free radicals, excitatory amino acids).Potentially break the ischemic-edema-herniation cycle sooner.Rationale for the Study: While DHC is effective for established MCE in non-EVT contexts and rescue DHC post-EVT is ineffective, high-quality evidence for early prophylactic DHC in high-risk large-core patients after successful EVT is lacking. Current guidelines do not address this specific, high-risk population where MCE incidence is \ 50% and outcomes are dismal despite recanalization. Study Aim: This trial will evaluate the efficacy and safety of early prophylactic decompressive hemicraniectomy compared to standard medical treatment (which includes rescue DHC if MCE develops) in AIS-LVO patients at high risk of MCE (defined by ASPECTS and NIHSS criteria) following successful EVT. The goal is to determine if proactive intervention can improve functional outcomes and reduce mortality in this critically ill population where current strategies fail.
Interventions
PROCEDUREEarly prophylactic decompressive hemicraniectomy
Early prophylactic decompressive hemicraniectomy (decompressive hemicraniectomy is required to initiate within 6 hours after completion of mechanical thrombectomy and within 4 hours after randomization).
Sponsors
Xuanwu Hospital, Beijing
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Premorbid mRS ≤1; 2. Time from symptom onset to puncture ≤24 hours; including wake-up stroke and unwitnessed stroke. The time at which symptoms began was defined as the "Last Known Well" (LKW). 3.18 to 75 years of age; 4.Internal carotid artery (ICA) or middle cerebral artery (MCA)-M1 occlusion confirmed by computed tomographic angiography (CTA)/ magnetic resonance angiography (MRA)/ digital subtraction angiography (DSA). Patients with involvement of ipsilateral anterior cerebral artery (ACA), MCA or embryonal posterior cerebral artery (PCA) are eligible for inclusion. 5.NIHSS1a ≥ 1 (with the clarification that changes in alertness cannot be attributable to cerebral edema); 6.Meeting any of the following criteria: 1. ASPECTS 3-5 and NIHSS ≥ 30; 2. ASPECTS 0-2; 7.Signs on CT/MRI of an infarct of at least 50% of the middle cerebral artery territory; 8.No midline shift or midline shift \<5mm; 9.Mechanical Thrombectomy and successful recanalization (defined as eTICI ≥2b50); 10.Ability to initiate decompressive hemicraniectomy within 6 hours after completion of mechanical thrombectomy and within 4 hours after randomization; 11.Informed consent obtained from the patient or his/her legal representative.
Exclusion criteria
Clinical
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of mRS score of 0-4 | 90 days (±7 days) after randomization | Rate of mRS score of 0-4 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of mRS score of 0-3 Ordinal shift analysis of mRS •Rate of mRS score of 0-2 •Rate of midline shift ≥ 5 mm •Rate of brain herniation Improvement of the NIHSS Rate of neurological deterioration Rate of rescue decompressive hemicraniectomy | 90 days (±7 days) after randomization | mRS score ranges 0-6 |
| Ordinal shift analysis of mRS | 90 days (±7 days) after randomization | mRS score ranges 0-6 |
| Rate of mRS score of 0-2 | 90 days (±7 days) after randomization | mRS score ranges 0-6 |
| Rate of midline shift ≥ 5 mm | Within 72 hours after randomization | Based on imaging assessment (e.g., CT, MRI) |
| Rate of brain herniation | Within 72 hours after randomization | e.g., 1 or 2 dilated, fixed pupils; unconsciousness related to edema \[i.e., ≥2 on item 1a on the NIHSS\]; and/or loss of other brain stem reflexes, attributable to edema or herniation according to the Investigator's judgment |
| Improvement of the NIHSS | 5-7 days after randomization or discharge | The NIHSS score range from 0 (no deficit) to 42 (maximum deficit) |
| Rate of neurological deterioration | 5-7 days after randomization or discharge | Defined as increase of NIHSS score ≥4 from baseline |
| Rate of rescue decompressive hemicraniectomy | 5-7 days after randomization or discharge | Control group |
| Length of ICU stay | Perioperative | Residual stay days of ICU |
| Length of hospitalization | Perioperative | Residual stay days of hospitalization |
| Barthel Index | 90 days (±7 days) after randomization | The Barthel Index range from 0 (severe disability) to 100 (no disability) |
| Modified Rankin scale and Barthel Index | 12 months (±30 days) after randomization | The mRS score range from 0 (no disability) to 6 (death), the Barthel Index range from 0 (severe disability) to 100 (no disability) |
| Rate of any intracranial hemorrhage (ICH) | Within 72 hours after randomization | The occurrence of ICH includes the following scenarios: 1. new occurrence of ICH; 2. progression of ICH based on Heidelberg Bleeding Classification. |
| Rate of parenchymal hematoma type 2 intracranial hemorrhage | Within 72 hours after randomization | — |
| Mortality | 90 days (±7 days) after randomization | Defined as mRS 6 |
| Serious Adverse Events | 90 days (±7 days) after randomization | Detailled description noted in study protocol |
Countries
China
Outcome results
None listed