LB-014 Final results of the ruptured aneurysms treated with hydrogel coils (RAGE) study: a multicenter North American study of 771 patients

Endovascular embolization of intracranial aneurysms with second-generation hydrogel coils lowers the risk of recurrence when compared to bare platinum coils, as demonstrated in the randomized controlled trial, HEAT. However, the proportion of ruptured aneurysms in existing studies is limited. The RAGE study is currently the largest prospective, single-arm, core lab adjudicated, multicenter, post-market study focusing exclusively on assessing the safety and effectiveness of HydroCoil Embolic System coils in the ruptured intracranial aneurysm population. Materials and Methods Subjects aged 18 to 80 years were eligible for enrollment if they had a previously untreated, ruptured saccular intracranial aneurysm between 2 and 15 mm in diameter, suitable for embolization with hydrogel coils. Inclusion criteria also required a Hunt and Hess score ≤III. Coiling was performed using any combination of second-generation hydrogel coils (HydroFrameTM, HydroFillTM, HydroSoftTM, HydroSoftTM 3D), with a minimum collective length of 90% of the total coil length used to treat the aneurysm. Study subjects were followed up clinically at 30 days and 18 months post-procedure with angiographic imaging collected at the 18-month visit. The primary efficacy endpoint was adequate angiographic occlusion at 18 ± 6 months without rebleed of the target aneurysm or retreatment secondary to aneurysm recurrence. The primary safety endpoint was procedure- or disease-related death or major stroke within 30 days of treatment or major ipsilateral stroke, neurological death or rebleeding from the target aneurysm within 18 months of treatment. Secondary outcomes included rebleed rate, retreatment rate, and clinical outcome. Rebleeds and other safety events were assessed by an independent clinical events adjudicator and an independent core lab adjudicated the angiographic outcomes. Results From November 2017 through September 2022, 771 subjects (mean age 53.8 years, 27.8% female) were enrolled across 43 sites in the US and two in Canada. Mean aneurysm size was 5.6 mm (range: 2-15mm) and the most common aneurysm locations were ACom (34%) and PCom (30%). 85.4% (455/533) of subjects had adequate angiographic occlusion at the 18-month visit. 76% (405/533) of subjects met the primary effectiveness endpoint of adequate angiographic occlusion at 18-month visit without rebleed of the target aneurysm or retreatment secondary to aneurysm recurrence. 6.1% (47/771) of subjects experienced a composite primary safety outcome event. Overall mortality rate was 4.8% (37/771) and the mRS score at 18 months was 0-2 in 87.5% (503/575) of subjects. Rebleed and retreatment rates at 18 months were 0.4% (3/771) and 13% (100/771) respectively, with retreatment due to recurrence within 18 months occurring in 10.1% (78/771) of subjects. Conclusion The RAGE study demonstrates that second-generation hydrogel coils are a safe and effective treatment option for ruptured intracranial aneurysms, with strong adequate angiographic occlusion rates (85.4%), exceptionally low rebleed rates (0.4%) and favorable neurologic outcomes (mRS 0-2 in 81.5%) at 18 months. As the largest prospective post-market study focused exclusively on this high-risk population, RAGE provides important long-term data that reinforces the clinical value of hydrogel coils in the management of ruptured aneurysms. Disclosures D. Fiorella: 1; C; Microvention/Teruma. 2; C; Microvention/Terumo. A. Arthur: 1; C; Microvention/Terumo. 2; C; Microvention/Terumo.