BAOCHE
Trial of Thrombectomy 6 to 24 Hours after Stroke Due to Basilar-Artery Occlusion
Year of Publication: 2022
Authors: Tudor G. Jovin, Chuanhui Li, Longfei Wu, ..., for the BAOCHE Investigators
Journal: The New England Journal of Medicine
Citation: N Engl J Med 2022;387:1373-84.
Link: https://www.nejm.org/doi/full/10.1056/NEJMoa2207576
PDF: https://www.nejm.org/doi/pdf/10.1056/NEJ...ticleTools=true
PDF: Clinical Question
In patients with acute ischemic stroke due to basilar-artery occlusion presenting 6 to 24 hours after symptom onset, does endovascular thrombectomy plus standard medical therapy improve functional outcomes compared with standard medical therapy alone?
Bottom Line
Thrombectomy plus medical therapy resulted in good functional status (mRS 0-3) at 90 days in 46% of patients vs. 24% with medical therapy alone (adjusted rate ratio 1.81; 95% CI, 1.26-2.60; P<0.001; NNT ~5). The trial was stopped early for efficacy at a prespecified interim analysis after 218 of planned 318 patients. However, thrombectomy was associated with more procedural complications (11%) and a numerically higher rate of symptomatic intracranial hemorrhage (6% vs. 1%).
Major Points
- Primary outcome positive: mRS 0-3 at 90 days was 46% (thrombectomy) vs. 24% (control), adjusted RR 1.81 (95% CI 1.26-2.60; P<0.001), NNT ~5.
- Original primary outcome (mRS 0-4) was null: 55% vs. 43% (adjusted RR 1.21; 95% CI 0.95-1.54) — primary endpoint was changed from mRS 0-4 to mRS 0-3 mid-trial (before unblinding) based on external data from BEST and BASICS.
- Functional independence (mRS 0-2) nearly tripled: 39% thrombectomy vs. 14% control (adjusted RR 2.75; 95% CI 1.65-4.56).
- Ordinal mRS shift favored thrombectomy: common odds ratio 2.64 (95% CI 1.54-4.50).
- Mortality was not significantly different: 31% thrombectomy vs. 42% control (adjusted RR 0.75; 95% CI 0.54-1.04).
- High reperfusion rate: mTICI 2b/3 achieved in 88% of thrombectomy patients; basilar-artery patency at 24 hours was 92% vs. 19%.
- Extended time window validated: benefit consistent in 6-12h window (RR 1.89) and >12-24h window (RR 1.71).
- sICH (SITS-MOST) was 6% vs. 1%; sICH (ECASS II) was 9% vs. 2%. NNH for sICH ~20.
- Procedural complications in 11%: vessel dissection (4%), vessel perforation (3%), distal embolization (5%). Rescue angioplasty/stenting needed in 55% of patients, reflecting high atherosclerotic burden.
- Trial stopped early after prespecified interim analysis of 212 patients crossed the O'Brien-Fleming boundary (P<0.012 threshold).
Design
Study Type: Investigator-initiated, multicenter, open-label, randomized, controlled trial with blinded outcome evaluation (PROBE design)
Randomization: 1
Blinding: Open-label treatment; blinded outcome assessment by local assessors unaware of treatment plus central assessors via video/audio recordings
Enrollment Period: August 2016 to June 2021
Follow-up Duration: 90 days (primary); also 6 and 12 months for EQ-5D-3L
Centers: 30
Countries: China
Sample Size: 218
Analysis: Intention-to-treat (ITT); also per-protocol (102 vs 100) and as-treated (113 vs 104). Stratified by age (≤70 or >70), time window (6-12h or >12-24h), baseline NIHSS (6-20 or >20).
Inclusion Criteria
- Age 18 to 80 years.
- Occlusion of the basilar artery or intracranial segments of both vertebral arteries.
- Treatable within 6 to 24 hours after symptom onset (last known well, excluding isolated vertigo).
- Pre-stroke modified Rankin Scale score of 0 or 1.
- NIHSS score ≥10 at presentation (amended to ≥6 after first 61 patients due to slow recruitment).
- PC-ASPECTS ≥6 on CT, CTA source images, or DWI-MRI.
- Pons-Midbrain Index ≤2 (1 point = infarction <50% one side; 2 points = ≥50% one side).
Exclusion Criteria
- Evidence of recent intracranial hemorrhage on imaging.
- Large posterior circulation infarct: PC-ASPECTS <6.
- Large brainstem infarct: Pons-Midbrain Index >2.
- Additional criteria detailed in Supplementary Table S1.
Baseline Characteristics
| Characteristic | Thrombectomy (N=110) | Control (N=107) |
|---|---|---|
| Age (mean±SD) | 64.2±9.6 | 63.7±9.8 |
| Male sex | 80 (73%) | 79 (74%) |
| Atrial fibrillation | 14 (13%) | 13 (12%) |
| Diabetes mellitus | 30 (27%) | 29 (27%) |
| Hypertension | 90/110 (82%) | 79/106 (75%) |
| Pre-stroke mRS 0 | 85 (77%) | 89 (83%) |
| NIHSS median (IQR) | 20 (15-29) | 19 (12-30) |
| NIHSS 6-20 | 66 (60%) | 61 (57%) |
| NIHSS >20 | 44 (40%) | 46 (43%) |
| Median SBP (IQR) | 157 (138-175) mmHg | 152 (138-166) mmHg |
| IV thrombolysis received | 15 (14%) | 23 (21%) |
| Median PC-ASPECTS (IQR) | 8 (7-10) | 8 (7-10) |
| Median Pons-Midbrain Index (IQR) | 1 (0-2) | 1 (0-2) |
| Occlusion site — Proximal basilar | 53/107 (50%) | 45/105 (43%) |
| Occlusion site — Middle basilar | 40/107 (37%) | 37/105 (35%) |
| Occlusion site — Distal basilar | 13/107 (12%) | 23/105 (22%) |
| Time window 6-12h | 64 (58%) | 71 (66%) |
| Time window >12-24h | 46 (42%) | 36 (34%) |
| Median onset-to-randomization (IQR) | 664 (512-861) min | 662 (492-838) min |
| Median onset-to-revascularization (IQR) | 790 (626-1000) min | |
| General anesthesia used | 72 (65%) |
Arms
| Field | Thrombectomy + Medical Therapy | Control |
|---|---|---|
| Intervention | Endovascular thrombectomy using Solitaire device (Medtronic) plus standard medical care per Chinese guidelines. Rescue balloon angioplasty or stenting of vertebral/basilar artery permitted. Intracranial angioplasty/stenting after failed thrombectomy performed in 60 patients (55%). General anesthesia in 65%. IV alteplase permitted if within 4.5h (14% received it). Admitted to acute stroke unit or neurologic ICU. | Standard acute ischemic stroke management per Chinese guidelines. Admitted to acute stroke unit or neurologic ICU. IV alteplase if within 4.5h (21% received it). 4 patients (3.7%) crossed over to endovascular treatment. |
| Duration | Single procedure + 90 days follow-up | 90 days follow-up |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| mRS 0-3 at 90 days | Primary | 26/107 (24%) | 51/110 (46%) | 5 | <0.001 |
| Ordinal mRS shift at 90 days | Secondary | — | — | Common OR 2.64 | |
| mRS 0-2 at 90 days | Secondary | 15/107 (14%) | 43/110 (39%) | Adjusted RR 2.75 | |
| mRS 0-4 at 90 days (original primary) | Secondary | 46/107 (43%) | 61/110 (55%) | Adjusted RR 1.21 | |
| Dramatic neurologic improvement at 24h (≥8pt NIHSS drop or 0-2) | Secondary | 9/94 (10%) | 25/101 (25%) | Adjusted RR 2.50 | |
| Barthel Index 95-100 at 90 days | Secondary | 10/56 (18%) | 26/73 (36%) | Adjusted RR 2.20 | |
| Basilar-artery patency at 24h | Secondary | 15/77 (19%) | 76/83 (92%) | Adjusted RR 4.53 | |
| Median EQ-5D-3L at 90 days | Secondary | 0.46 (IQR 0.11-0.73) | 0.78 (IQR 0.36-1.00) | Mean diff 0.24 | |
| Successful reperfusion (mTICI 2b/3) | Secondary | N/A | 89/101 (88%) | ||
| Death within 90 days | Adverse | 45/107 (42%) | 34/110 (31%) | Adjusted RR 0.75 | |
| sICH — SITS-MOST | Adverse | 1/88 (1%) | 6/102 (6%) | RR 5.18 | |
| sICH — ECASS II | Adverse | 2/88 (2%) | 9/102 (9%) | RR 3.88 | |
| Asymptomatic ICH | Adverse | 3/88 (3%) | 8/102 (8%) | RR 2.30 | |
| Procedural complications | Adverse | N/A | 12/110 (11%) | ||
| Vessel dissection | Adverse | N/A | 4 (4%) | ||
| Vessel perforation | Adverse | N/A | 3 (3%) | ||
| Distal embolization | Adverse | N/A | 5 (5%) | ||
| Pneumonia | Adverse | 50 (47%) | 51 (46%) | ||
| Malignant brain edema | Adverse | 11 (10%) | 14 (13%) | ||
| GI hemorrhage | Adverse | 10 (9%) | 15 (14%) | ||
| Acute heart failure | Adverse | 22 (21%) | 16 (15%) | ||
| Acute respiratory failure | Adverse | 26 (24%) | 21 (19%) |
Subgroup Analysis
No significant interactions reported. Benefit of thrombectomy was consistent across subgroups: age ≤70 (RR 1.70) vs >70 (RR 3.04); male (RR 1.61) vs female (RR 2.95); NIHSS 6-20 (RR 1.80) vs >20 (RR 1.83); 6-12h (RR 1.89) vs >12-24h (RR 1.71); PC-ASPECTS ≥9 (RR 1.42) vs <9 (RR 2.17); proximal (RR 1.96) vs middle (RR 1.67) basilar occlusion. Trial not powered for subgroup analyses.
Criticisms
- Primary outcome changed mid-trial from mRS 0-4 to mRS 0-3 (though before unblinding, based on external BEST/BASICS data). Original primary (mRS 0-4) was null.
- Open-label design, though outcome assessment was blinded.
- Limited to Han Chinese population — generalizability uncertain, especially for embolic vs atherothrombotic etiology.
- 101 of 319 excluded patients underwent endovascular therapy outside the trial — selection bias.
- Low IV thrombolysis rate (14-21%) — patients had to pay for the drug; less than two-thirds arriving within 4.5h received it.
- Early stopping for efficacy after 218 of 318 planned patients may overestimate treatment effect.
- Original primary outcome (mRS 0-4) had CI crossing 1.0 (RR 1.21, 0.95-1.54).
- Rescue intracranial angioplasty/stenting was needed in 55%, reflecting predominantly atherosclerotic etiology that may differ from Western populations.
Funding
Chinese National Ministry of Science and Technology (Grant 2016YFC1301502). No industry involvement.
Based on: BAOCHE (The New England Journal of Medicine, 2022)
Authors: Tudor G. Jovin, Chuanhui Li, Longfei Wu, ..., for the BAOCHE Investigators
Citation: N Engl J Med 2022;387:1373-84.
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