Early Prophylactic Decompressive Hemicraniectomy Following Endovascular Therapy in Large Hemispheric Infarct Trial

NCT ID: NCT07118345

Last Updated: 2026-01-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 380 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-19
• Study Completion Date: 2029-06-19

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.

Conditions

Stroke, Ischemic; Cerebral Edema

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental group

Early prophylactic decompressive hemicraniectomy

Group Type: EXPERIMENTAL

Early prophylactic decompressive hemicraniectomy

Intervention Type: PROCEDURE

Early prophylactic decompressive hemicraniectomy (decompressive hemicraniectomy is required to initiate within 6 hours after completion of mechanical thrombectomy and within 4 hours after randomization).

Control group

Standard medical treatment (with or without rescue decompressive craniectomy if needed).

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Early 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).

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

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

1. Any symptoms and signs of brain herniation before randomization, such as pupil anisocoria and unstable vital signs.

2. In the judgment of the investigator, the subject is likely to have supportive care withdrawn in the first day.

3. Commitment to decompressive hemicraniectomy (DHC) prior to enrollment.

4. Severe, sustained hypertension (systolic blood pressure > 220 mm Hg or diastolic blood pressure > 110 mm Hg);

5. Baseline blood glucose <50 mg/dl (2.8 mmol/L) or >400 mg/dl (22.2 mmol/L);

6. Baseline platelet count <100 x10^9/L;

7. Known hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with international normalized ratio > 1.7;

8. Severe renal insufficiency, defined as serum creatinine > 3.0 mg/dl (or 265.2 μmol/l) or glomerular filtration rate [GFR] < 30 ml/min, or patients requiring hemodialysis or peritoneal dialysis;

9. Patients that cannot complete 90-day follow-up (such as no fixed residence, overseas patients, etc.);

10. Suspected vasculitis or septic embolism;

11. Neurological diseases or mental disorders before onset that affect the assessment of the condition;

12. Females who are pregnant or in lactation;

13. Participating in other clinical trials that could confound the evaluation of the study;

14. Subjects who, in the opinion of the investigator, have a life expectancy <3 months due to conditions not related to current LHI or are unlikely to comply with follow-up requirements. Other conditions that the investigators believe are not suitable for participation or may pose a significant risk to the patient.

1. Evidence of other brain diseases such as cerebral trauma, intracranial tumor (except small meningioma), cerebral aneurysm, etc.

2. Evidence of acute ischemic infarction in bilateral anterior circulation territory or involvement of posterior circulation territories (other than in patients with a fetal or near-fetal PCA configuration);

3. Vascular perforation during thrombectomy;

4. The pre-randomization CT findings exhibits evidence of parenchymal hemorrhage 2 intracranial hemorrhage, diffuse severe subarachnoid hemorrhage, or intraventricular hemorrhage. Patients with localized mild subarachnoid hemorrhage, hemorrhagic infarction type1 or 2, and small parenchymal hematoma type 1 without midline shift may be included;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Xuanwu Hospital, Beijing

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Xuanwu Hospital, Capital Medical University.

Beijing, , China

Site Status: NOT_YET_RECRUITING

Liaocheng Brain Hospital

Shandong, , China

Site Status: RECRUITING

Countries

China

Facility Contacts

Liqun Jiao, MD.

Role: primary

jiaoliqun@xwhosp.org

86+13911224991

Liyong Zhang, MD.

Role: primary

13346256936@163.com

86+13346256936

Other Identifiers

IAT-EPIC

Identifier Type: -

Identifier Source: org_study_id