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(2015)Objective
To evaluate whether early thrombectomy using Solitaire improves outcomes compared to alteplase alone in patients with LVO and salvageable tissue.
Study Summary
• Thrombectomy with Solitaire after alteplase led to better reperfusion, early neurologic improvement, and improved functional outcomes versus alteplase alone.
Intervention
IV alteplase (0.9 mg/kg) with or without Solitaire thrombectomy. Endovascular therapy started within 6 hours after onset and completed within 8 hours.
Inclusion Criteria
Acute anterior circulation stroke, within 4.5 hours from onset, LVO (ICA/M1/M2), salvageable tissue and ischemic core <70 mL on perfusion imaging, mRS <2 before stroke.
Study Design
Arms: Thrombectomy + Alteplase vs. Alteplase Alone
Patients per Arm: Thrombectomy: 35, Alteplase: 35
Outcome
• Primary: Reperfusion at 24h: median 100% vs. 37%, P<0.001. Early neurologic improvement: 80% vs. 37%, P=0.002.• mRS 0–2 at 90d: 71% vs. 40%, P=0.01.• Median mRS at 90d: 1 vs. 3.• mRS shift analysis: OR 2.0, P=0.006.• sICH: 0% vs. 6%.• Mortality: 9% vs. 20%.• Parenchymal hematoma: 11% vs. 9%.• Reperfusion >90% at 24h without sICH: 89% vs. 34%, P<0.001.• Median infarct growth: 10.9 vs. 35.3 mL.• Median home time at 90d: 73 vs. 15 days.
Bottom Line
Endovascular thrombectomy with the Solitaire device significantly improved early reperfusion, functional outcomes, and reduced infarct growth compared to IV tPA alone in patients with large-vessel occlusion and favorable imaging profile.
Major Points
- One of five landmark 2015 thrombectomy RCTs. Unique contribution: first to use automated CT perfusion (RAPID software) for patient selection and first to demonstrate perfusion imaging-guided thrombectomy efficacy.
- Conducted in Australia and New Zealand (14 centers) — the only 2015 trial from the Southern Hemisphere.
- Stopped early after just 70 patients (target 100) at the first planned interim analysis — the smallest of the 2015 trials but with the largest effect sizes.
- Primary outcome was reperfusion at 24h on perfusion imaging: 100% thrombectomy vs 37% control (p<0.001) — a near-perfect primary endpoint.
- Functional independence (mRS 0–2 at 90 days): 71% vs 40% (OR 3.1, p=0.01) — the highest absolute rate of independence in any 2015 thrombectomy trial.
- Median 24h infarct volume: 13 mL thrombectomy vs 57 mL control (p<0.001) — demonstrating that thrombectomy dramatically reduces infarct growth.
- Pioneered use of RAPID automated perfusion software for patient selection: ischemic core <70 mL, mismatch ratio >1.2. This became the standard imaging paradigm for DAWN, DEFUSE 3, and subsequent trials.
- Occlusion sites: ICA or proximal MCA (M1). Required IV tPA eligibility (bridging therapy mandatory, similar to SWIFT PRIME).
- 90-day mortality: 9% vs 20% (p=0.18) — numerically the largest mortality reduction among 2015 trials, though not significant due to small sample size.
- sICH: 6% thrombectomy vs 0% control (p=0.49) — higher in intervention group, though not significant; highlights that highly selected patients still carry procedural risk.
- Solitaire FR stent retriever was the exclusive device used — results specific to this device platform.
Study Design
- Study Type
- Prospective, randomized, open-label, blinded endpoint (PROBE) multicenter trial
- Randomization
- Yes
- Blinding
- Outcome assessors were blinded; patients and physicians were unblinded
- Sample Size
- 70
- Follow-up
- 90 days
- Centers
- 14
- Countries
- Australia, New Zealand
Primary Outcome
Definition: Percentage of ischemic territory reperfused at 24 hours as measured by perfusion imaging
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 37% | 100% | - | <0.001 |
Limitations & Criticisms
- Smallest of the 2015 thrombectomy trials (n=70) — stopped at first interim analysis, raising concerns about effect size overestimation.
- Highly selected population: required CT perfusion with automated RAPID software, IV tPA eligibility, and favorable mismatch profile — may not generalize to patients without perfusion imaging access.
- Open-label design (PROBE) — knowledge of treatment assignment could influence post-procedure care intensity and rehabilitation referral patterns.
- 100% reperfusion rate at 24h in control group seems high for IV tPA alone — may reflect favorable patient selection or perfusion imaging threshold effects.
- sICH was numerically higher in thrombectomy group (6% vs 0%), though not significant — concerning signal in such a small trial.
- Exclusive use of Solitaire FR device — results cannot be directly extrapolated to aspiration-first techniques or other device platforms.
- Australia/New Zealand healthcare system context — workflow and access patterns may differ from North American and European settings.
- CT perfusion availability required at enrolling sites — limits applicability in settings without 24/7 perfusion imaging capability.
- Mandatory IV tPA excludes patients with contraindications to thrombolysis — later studies (MR CLEAN subgroups) showed benefit of direct thrombectomy.
Citation
N Engl J Med 2015;372:1009–18