PDF: FRED
(2021)Objective
To evaluate the safety and efficacy of the Flow Re-Direction Endoluminal Device (FRED) for treating intracranial aneurysms.
Study Summary
Intervention
Treatment with the FRED flow diverter device in patients with intracranial aneurysms, followed over 12 months to assess angiographic and clinical outcomes.
Inclusion Criteria
Adults with unruptured intracranial aneurysms measuring 4–30 mm, suitable for treatment with a flow diverter, and located in the anterior circulation (internal carotid artery segment from petrous to superior hypophyseal).
Study Design
Arms: Single-arm trial using FRED device.
Patients per Arm: FRED: 145 enrolled, 143 treated, 121 had 1-year imaging follow-up.
Outcome
Bottom Line
The FRED flow diverter met both FDA performance goals: primary safety endpoint (death/major stroke ≤30 days or major ipsilateral stroke/neurological death ≤1 year) was 6.2% (9/145), well below the <15% threshold. Complete aneurysm occlusion with ≤50% stenosis and no retreatment at 12 months was 57.6% (80/139), exceeding the >46% goal. Disabling/fatal neurological events occurred in only 2.8% (4/145).
Major Points
- Primary safety met: 9/145 (6.2%) composite safety events, below <15% performance goal (posterior probability 0.999).
- Low disabling morbidity/mortality: only 4/145 (2.8%) experienced disabling stroke (mRS >2) or death.
- Primary effectiveness exceeded goal: 80/139 (57.6%) complete occlusion + no stenosis + no retreatment at 12 months, above >46% threshold.
- Near-complete (90-100%) occlusion: 100/139 (71.9%). Complete Raymond 1 alone: 88/140 (62.9%).
- Predominantly large/giant aneurysms: 73.1% were >10mm (core lab); mean dome height 11.5mm.
- Single-device treatment in 93.1% (vs Pipeline PUFS median 3 devices).
- Device thrombosis 8.3% (12/145) — all 8 periprocedural events resolved with IIb/IIIa inhibitors.
- PComA location had disproportionate stroke risk: 5/6 major strokes within 30 days (P<0.001).
- Parent artery stenosis ≥50%: only 4.3% (6/139) at 12 months.
- Retreatment rate 5.7% (8/140) within 12 months; device migration/foreshortening in ≥3 failures.
Study Design
- Study Type
- Prospective, multicenter, single-arm, investigational device exemption (IDE) pivotal trial
- Randomization
- No
- Blinding
- Independent blinded Clinical Events Committee; independent blinded DSMB; independent angiographic core laboratory.
- Sample Size
- 145
- Follow-up
- 12 months (clinical at 30d, 90d, 180d, 1yr; angiographic at 180d and 1yr)
- Centers
- 23
- Countries
- United States, Japan
Primary Outcome
Definition: Safety: death/major stroke ≤30 days or major ipsilateral stroke/neurological death ≤12 months. Effectiveness: complete occlusion (Raymond 1) + ≤50% parent artery stenosis + no retreatment at 12 months.
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| Performance goals: safety <15%, effectiveness >46% | Safety: 9/145 (6.2%). Effectiveness: 80/139 (57.6%). | - (Safety: 3.3-11.3%. Effectiveness: 49.2-65.5%.) | Posterior probability >0.975 for both |
Limitations & Criticisms
- No control group — single-arm with historically derived performance goals.
- Performance goals developed by sponsor (Microvention) with FDA — potential selection bias in literature chosen.
- PComA clustering of major strokes unexplained — no device-specific mechanism identified.
- Protocol violation: 1 patient with AF enrolled (exclusion criterion) — resulted in neurological death.
- 12-month follow-up only — flow diverter occlusion rates increase beyond 1 year.
- Antiplatelet testing not required — clopidogrel resistance not evaluated.
- Industry funded (Microvention-Terumo); multiple authors are consultants.
Citation
J NeuroIntervent Surg. 2022;14:577-584.