Eradicating Barrett's Esophagus Using Radiofrequency Ablation or a Novel Hybrid Argon Plasma Coagulation Technique

Barrett's Esophagus (BE) is a pre-malignant condition and may progress to low grade dysplasia, high grade dysplasia and ultimately esophageal adenocarcinoma which has poor prognosis with a 5-year survival rate of only 5 - 20 %. Radiofrequency ablation (RFA) is a standard modality and well-studied endoscopic treatment for dysplastic BE. HybridAPC® (HAPC) is a newer technique for endoscopic treatment of dysplastic BE that involves submucosal fluid injection prior to performing APC. The study aim of this non-inferiority study is to show that HAPC is at least as safe and effective as RFA in the stricture-free eradication of dysplasia (CE-D).

The study is a multi-center, parallel group (HAPC/RFA) prospective, single blind, non-inferiority, randomized controlled study to assess the safety and effectiveness of HAPC (treatment arm) compared to RFA (control arm) in the treatment of BE in up to 144 male and female adult patients. Participants of the study will be enrolled in up to 15 centers in the US. Both techniques have never been directly compared in the treatment of BE.

The specific aim of this non-inferiority study is to show that HAPC is at least as safe and effective as RFA in the stricture-free eradication of dysplasia (CE-D), by inducing complete eradication of dysplasia (CE-D) within 12 months after last treatment as confirmed by endoscopy and histology.

HybridAPC® is an endoscopic technique that is used with the HybridAPC® Probe, the Water Jet Model ERBEJET 2 and an ERBE Argon Plasma Coagulator (APC) Model APC 2/Electrosurgical Unit (ESU) VIO Model System. The Water Jet delivers pressurized sterile 0.9 % sodium chloride solution (normal saline) through the HybridAPC® Probe into the submucosa of the Barrett mucosa. Reduction/limitation of unwanted tissue damage (penetration depth) is being ensured by the saline cushion when applying argon plasma coagulation to ablate Barrett's mucosa with subsequent regeneration of esophageal squamous mucosa.

Radiofrequency ablation (RFA) applied in the control arm using BarrxTM FLEX RFA Generator is an endoscopic technique that delivers high radiofrequency waves using either circumferential (balloon inserted over an endoscopically placed guidewire) device of focal (probe attached to the tip of the endoscope) device to damage the Barrett's mucosa with subsequent regeneration of esophageal squamous mucosa. While a circumferential device can be used to treat larger BE areas, focal device (Halo 60, 90 or through the scope device) can be used to treat small islands of residual BE. The depth of the injury is controlled by regular spacing of the electrodes and the delivery of a pre-set amount of energy through the probes. The PI/Co-investigators will be instructed to operate the BarrxTM FLEX RFA Generator and above referenced catheters according to the cleared labeling.

Patients with dysplastic BE will be identified at each participating center, and defined as those with LGD within previous 6 months and HGD/cancer within previous 6 months, both timed from date of consent. All histology slides from biopsies and endoscopic mucosal resection (EMR) specimens will be read by the local pathologist for patient management purposes and separately by a single independent reference pathologist to confirm patient eligibility for randomization.

Eligible patients will be block randomized at each participating study center at a ratio of 1 : 1 to receive treatment of dysplasia with HAPC or RFA after EMR of visible lesions (if present) has been performed as per standard of care. All patients will be assigned a unique registration number allocated by the Electronic Data Capture (EDC) system following details submitted on a web form. Due to the nature of the intervention only the patient will be blinded (single blinding), and not the PI or Co-investigators. The assigned HAPC ablation or RFA procedure will be performed at 8 to 12-week intervals until eradication of BE has been achieved. A maximum number of 4 treatment sessions is allowed.

Once the BE has been eradicated endoscopically, 4 quadrant biopsies every 1-2 cm will be performed to confirm complete eradication of dysplasia/IM (standard of care) and slides sent for confirmation by the central pathologist.

Primary statistical analysis will compare the proportions of patients in whom stricture-free eradication of dysplastic BE has been achieved.

As secondary endpoints complete endoscopic and histological eradication of intestinal metaplasia (CE-IM), stricture rate, post-operative pain, cost-effectiveness and recurrence of intestinal metaplasia and dysplasia will be documented and reported. No formal tests of hypothesis will be applied for these secondary endpoints.

Data from the trial will be entered into a database (VISION EDC, version 8, Prelude Dynamics, Austin, TX) and all statistical analyses will be performed using validated software (SAS, version 9.4; IBM/SPSS, version 23; Cytel StatXact, version 11; or R).