The Instylla HES Hypervascular Tumor Study: A Prospective, Randomized, Multicenter Study of a Liquid Embolic for Treatment of Hypervascular Tumors

Purpose: A prospective, randomized, multicenter study to evaluate the safety and effectiveness of the Instylla Hydrogel Embolic System (HES) for the vascular occlusion of hypervascular tumors (HVT) compared with standard of care (SOC).

Materials and Methods: Instylla HES is a biocompatible, persistent, polyethylene glycol liquid embolic provided as a two-part system that forms a hydrogel in situ at the target location.  A total of 150 men (84) and women (66), average age 65.4 years, presenting with HVT were recruited from 22 centers in this investigational study.  Patients were randomized 2:1 to the Instylla HES treatment or the institutional SOC transarterial embolization/conventional chemoembolization (TAE/cTACE).  Clinical and imaging follow-up was conducted at 30 and 90 days with clinical follow-up at 180 days.

The primary safety endpoint was freedom from major adverse events (MAE) through 30 days compared to a literature-derived performance goal of 75%.  An MAE was defined as definitely or probably attributable to the device and/or procedure and Grade ≥ 3 events per the 2017 Society of Interventional Radiology (SIR) Guidelines for events of death, non-target embolization, unintended target tissue ischemia, pulmonary embolism, vascular injury requiring intervention, renal or hepatic failure, abscess in target organ/tissue, or toxic/allergic reaction to HES.  The primary effectiveness endpoint (Technical Success) was the delivery of the embolic agent to the index tumor feeding vessel with stasis of flow assessed by an independent imaging core laboratory.  Local response of treated tumors via contrast-enhanced CT or MRI imaging was also assessed.

Results: Preliminary results show the study met the primary safety endpoint wherein Freedom from MAE was 99.0% (lower 95% CI = 95.15%, p-value < 0.001), with a single event attributed to the procedure. The analysis for Technical Success was based on 132 vessels in 97 subjects receiving HES and 66 vessels in 48 subjects receiving SOC. The primary effectiveness endpoint met the non-inferiority margin of 10%; Technical Success was 88.6% vs. 77.3% for HES and SOC, respectively, difference 10.9% (95% CI= -2.42%, 24.28%, P=0.001).

Conclusion: This first, randomized pivotal study of a peripheral liquid embolic demonstrates that the Instylla HES met its primary endpoints for safety and effectiveness in the treatment of hypervascular tumors. The HES is an investigational device not available for commercial use.