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

Not Applicable

Completed

• Conditions: Barrett Esophagus

• Registration Number: NCT00489268
• Lead Sponsor: Covidien, GI Solutions

Brief Summary

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

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.

Study Timeline

• Study Start: 2003-11
• Primary Completion: 2007-02
• Study First Submitted: 2007-06-19
• Study First Submitted QC: 2007-06-20
• Study First Posted: 2007-06-21
• Study Completion: 2009-10
• Results First Submitted: 2011-03-07
• Results First Submitted QC: 2011-06-06
• Results First Posted: 2011-06-30
• Status Verified: 2017-01
• Last Update Submitted: 2017-01-31
• Last Update Posted: 2017-03-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 102

Inclusion Criteria

1. 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

2. Barrett metaplasia endoscopic length:

   Phase I : 2-3 cm Barrett's length (inclusive) Phase II: 2-6 cm Barrett's length (inclusive)

3. Age 18-75 years inclusive

4. Subject agrees to participate, fully understands content of informed consent form, and signs the informed consent form

5. 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

1. Subjects is pregnant or planning a pregnancy
2. Esophageal stricture preventing passage of endoscope or catheter
3. Active esophagitis (Hetzel-Dent Grade III or IV) described as erosions or ulcerations encompassing more than 10% of distal esophagus
4. Barrett's metaplasia with dysplasia (any previous biopsy)
5. History or current diagnosis of malignancy of the esophagus
6. Prior radiation therapy to the esophagus, except head and neck region radiation therapy
7. Any previous ablative therapy within the esophagus (photodynamic therapy, multipolar electrical coagulation, argon plasma coagulation, laser treatment, or other)
8. Any previous endoscopic mucosal resection within the esophagus
9. Any previous esophageal surgery, except fundoplication
10. Esophageal varices
11. 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
12. Participation in another clinical study in past 60 days
13. Subject suffers from unstable psychiatric disorder(s)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Histological Clearance of Barrett's Metaplasia	5 year	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).

Secondary Outcome Measures

Name	Time	Method
Progression of Histological Grade	5 year	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.
Adverse Events	5 year	The secondary outcome adverse events was defined as any event that occurred during the course of the trial
Percentage of Participants With Sub-squamous Intestinal Metaplasia	5 year	The secondary outcome sub-squamous intestinal metaplasia was defined as prevalence of buried glandular mucosa in the esophagus.

Trial Locations

Locations (10)

Mayo Clinic Scottsdale; 🇺🇸 Scottsdale, Arizona, United States

UC Irvine Medical Center; 🇺🇸 Orange, California, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

Mayo Clinic Rochester; 🇺🇸 Rochester, Minnesota, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

Oregon Health Sciences University; 🇺🇸 Portland, Oregon, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Gastrointestinal Associates; 🇺🇸 Knoxville, Tennessee, United States

Tacoma Digestive Disease and Research Center; 🇺🇸 Seattle, Washington, United States

Ponce Gastroenterology Research; 🇵🇷 Ponce, Puerto Rico