Micro-Layer Ablation of Barrett's Metaplasia- A Two-Phase, Multi-Center Trial - Extension of Follow-up to 5 Years

Study Overview
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Brief Summary
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This study was conducted in 2 serial phases (dosimetry phase and effectiveness phase) to evaluate a balloon-based ablation device (HALO360) that delivers a pre-set amount of energy density (J/cm2) to barrett's tissue. The dosimetry phase evaluated the dose-response and the safety of delivering 6 to 12 J/cm2. The effectiveness phase used 10 J/cm2 delivered twice for all patients, followed by Esophagogastroduodenoscopy (EGD) with biopsies at 1, 3, 6, and 12 months. A second ablation procedure was performed if Barretts esophagus (BE) was present at 1 or 3 months. A complete response (CR) was defined as all biopsy specimens negative for Barrett's Esophagus at 12 months. The effectiveness phase of the present study was extended to a 2.5-year follow-up. This trial incorporated an opportunity for persistent BE to be treated with a focal ablation device (HALO90), achieving a CR in 98.4% of patients by the 2.5-year follow-up,the results of which were published . There is ample evidence that RadioFrequency Ablation (RFA) for Barrett's esophagus is effective and safe. Having additional follow-up (5 years) would add valuable information to the literature, thus aiding the physician in making patient management decisions about the appropriate follow-up interval after RFA.

Detailed Description
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This study is intended to gather additional information regarding the performance of a bipolar balloon electrode device (HALO360) utilizing radiofrequency (RF) energy in the micro-layer ablation of Barrett's esophagus, a precancerous, metaplastic change in the esophageal lining. The device has received 510(k) clearance for specific indications, including the treatment of Barrett's esophagus. This study is conducted in two phases and is intended to further evaluate the effect of micro-layer ablation of Barrett's metaplasia using a 510(k) cleared, bipolar, balloon electrode device. Phase I (n=30) is intended to provide additional information regarding the effects of three randomized treatment parameters (energy settings, Joules/cm2). Phase II (n=70) is intended to provide additional information regarding the effects of the optimal technique and energy density settings (Joules/cm2) determined from the 1-month endoscopy results of Phase I. Phase 2 primary endpoint was histological clearance of Barrett's (% patients). This trial incorporated an opportunity for persistent BE to be treated with a focal ablation device (HALO90), at the 2.5-year follow-up, achieving a CR in 98.4% of patients. Having additional follow-up (5 years) would add valuable information to the literature, thus aiding the physician in making patient management decisions about the appropriate follow-up interval after RFA. This study will allow collection of 5-year follow-up biopsies and, thereafter, offer RFA for any subject with persistent Barrett's. Upon approval of the present amendment to the protocol (B-200-5 year extension) and the informed consent form (ICF) at each study site, subjects who participated in B-200-2.5 year extension and had a biopsy at 2.5 years after initial enrollment will be offered participation in this extension.

Official Title
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Micro-Layer Ablation of Barrett's Metaplasia- A Two-Phase, Multi-Center Trial - Extension of Follow-up to 5 Years

Conditions
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Barrett Esophagus

Intervention / Treatment
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* Device: HALO Ablation System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has documented histopathological diagnosis of Barrett's metaplasia (without dysplasia) as follows: biopsies obtained less than 6 months prior to enrollment, and biopsies obtained and reviewed at the investigator institution, and biopsy protocol included at least 4 quadrant biopsies per 2 cm length of Barrett's metaplasia Barrett metaplasia endoscopic length: Phase I : 2-3 cm Barrett's length (inclusive) Phase II: 2-6 cm Barrett's length (inclusive) Age 18-75 years inclusive Subject agrees to participate, fully understands content of informed consent form, and signs the informed consent form Five year extension: All subjects who participated in B-200-2.5 year extension and had a biopsy at 2.5 years after initial enrollment (n=61) will be offered participation in this extension. Exclusion Criteria: Subjects is pregnant or planning a pregnancy Esophageal stricture preventing passage of endoscope or catheter Active esophagitis (Hetzel-Dent Grade III or IV) described as erosions or ulcerations encompassing more than 10% of distal esophagus Barrett's metaplasia with dysplasia (any previous biopsy) History or current diagnosis of malignancy of the esophagus Prior radiation therapy to the esophagus, except head and neck region radiation therapy Any previous ablative therapy within the esophagus (photodynamic therapy, multipolar electrical coagulation, argon plasma coagulation, laser treatment, or other) Any previous endoscopic mucosal resection within the esophagus Any previous esophageal surgery, except fundoplication Esophageal varices Subject has an implantable pacing device (examples; AICD, neurostimulator, cardiac pacemaker) and has not received clearance for enrollment in this study by specialist responsible for the pacing device Participation in another clinical study in past 60 days Subject suffers from unstable psychiatric disorder(s)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Phase I: 6 J/cm2<br>Subjects randomized to the energy density group of 6 J/cm2 through the HALO Ablation System. | Device: HALO Ablation System<br>* Phase I: 1-2 ablation visits; Phase II 1 to 12 months: 1-2 ablation visits; Phase II 12 to 30 months: 1-3 ablation visits Phase II 55-60 months: 0-1 ablation visit ******Phase I was a dosimetry study and Phase II used the preferred dose. The same intervention was used for each dose.<br>* Other names: HALO90;|
| Active Comparator: Phase I: 8 J/cm2<br>Subjects randomized to the energy density group of 8 J/cm2 through the HALO Ablation System. | Device: HALO Ablation System<br>* Phase I: 1-2 ablation visits; Phase II 1 to 12 months: 1-2 ablation visits; Phase II 12 to 30 months: 1-3 ablation visits Phase II 55-60 months: 0-1 ablation visit ******Phase I was a dosimetry study and Phase II used the preferred dose. The same intervention was used for each dose.<br>* Other names: HALO90;|
| Active Comparator: Phase I: 10 J/cm2<br>Subjects randomized to the energy density group of 10 J/cm2 through the HALO Ablation System. | Device: HALO Ablation System<br>* Phase I: 1-2 ablation visits; Phase II 1 to 12 months: 1-2 ablation visits; Phase II 12 to 30 months: 1-3 ablation visits Phase II 55-60 months: 0-1 ablation visit ******Phase I was a dosimetry study and Phase II used the preferred dose. The same intervention was used for each dose.<br>* Other names: HALO90;|
| Active Comparator: Phase I: 12 J/cm2<br>Subjects randomized to the energy density group of 12 J/cm2 through the HALO Ablation System. | Device: HALO Ablation System<br>* Phase I: 1-2 ablation visits; Phase II 1 to 12 months: 1-2 ablation visits; Phase II 12 to 30 months: 1-3 ablation visits Phase II 55-60 months: 0-1 ablation visit ******Phase I was a dosimetry study and Phase II used the preferred dose. The same intervention was used for each dose.<br>* Other names: HALO90;|
| Active Comparator: Phase II<br>All Halo 360 treatments performed at 10 J/cm2 through the HALO Ablation System. All Halo 90 treatments performed at 12 J/cm2 through the HALO Ablation System. | Device: HALO Ablation System<br>* Phase I: 1-2 ablation visits; Phase II 1 to 12 months: 1-2 ablation visits; Phase II 12 to 30 months: 1-3 ablation visits Phase II 55-60 months: 0-1 ablation visit ******Phase I was a dosimetry study and Phase II used the preferred dose. The same intervention was used for each dose.<br>* Other names: HALO90;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Histological Clearance of Barrett's Metaplasia | The primary study outcomes were defined as the percent of patients with complete histological response to intestinal metaplasia (IM) (CR-IM). CR-IM means complete eradication of IM (diseased epithelium). A patient was considered a Complete Responder (CR) if all biopsies (100%) were negative for intestinal metaplasia (CR-IM). | 5 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression of Histological Grade | Secondary outcomes of progression of histological grade was defined as proportion of participants who had progression of disease such as (i) prevalence of dysplasia; (ii) Kaplan-Meier CR-IM (Complete Response to Intestinal Metaplasia) survival analysis. | 5 year | 
| Adverse Events | The secondary outcome adverse events was defined as any event that occurred during the course of the trial | 5 year | 
| Percentage of Participants With Sub-squamous Intestinal Metaplasia | The secondary outcome sub-squamous intestinal metaplasia was defined as prevalence of buried glandular mucosa in the esophagus. | 5 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Barrett's Esophagus, Intestinal Metaplasia, Radiofrequency Ablation