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

Barrett Esophagus Clinical Trial

— AIM  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00489268
• Other study ID #: B-200
• Status: Completed
• Phase: N/A
• First received: June 19, 2007
• Last updated: June 6, 2011
• Start date: November 2003
• Est. completion date: October 2009

Study information

• Verified date: June 2011
• Source: Covidien, GI Solutions
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 102
• Est. completion date: October 2009
• Est. primary completion date: February 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Barrett Esophagus
• Metaplasia

Intervention

Device:
• HALO Ablation System
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

Locations

Country	Name	City	State
Puerto Rico	Ponce Gastroenterology Research	Ponce
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Gastrointestinal Associates	Knoxville	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	UC Irvine Medical Center	Orange	California
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Oregon Health Sciences University	Portland	Oregon
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	Tacoma Digestive Disease and Research Center	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Covidien, GI Solutions	AstraZeneca

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (3)

Fleischer DE, Overholt BF, Sharma VK, Reymunde A, Kimmey MB, Chuttani R, Chang KJ, Lightdale CJ, Santiago N, Pleskow DK, Dean PJ, Wang KK. Endoscopic ablation of Barrett's esophagus: a multicenter study with 2.5-year follow-up. Gastrointest Endosc. 2008 N — View Citation

Fleischer DE, Overholt BF, Sharma VK, Reymunde A, Kimmey MB, Chuttani R, Chang KJ, Muthasamy R, Lightdale CJ, Santiago N, Pleskow DK, Dean PJ, Wang KK. Endoscopic radiofrequency ablation for Barrett's esophagus: 5-year outcomes from a prospective multicen — View Citation

Sharma VK, Wang KK, Overholt BF, Lightdale CJ, Fennerty MB, Dean PJ, Pleskow DK, Chuttani R, Reymunde A, Santiago N, Chang KJ, Kimmey MB, Fleischer DE. Balloon-based, circumferential, endoscopic radiofrequency ablation of Barrett's esophagus: 1-year follo — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Histological Clearance of Barrett's Metaplasia (Percent Patients)	The primary study outcomes were defined as the percent of patients with complete histological response to metaplasia or IM (CR-IM).	5 year	No
Secondary	Progression of Histological Grade	Secondary outcomes of progression of histological grade was defined as proportion of participants had progression of disease such as (i) prevalence of dysplasia; (ii) Kaplan-Meier CR-IM (Complete Response to Intestinal Metaplasia) survival analysis, the Kaplan-Meier survival curve shows the probability of maintaining CR-IM for at least 4 years after first durable CR-IM.	5 year	No
Secondary	Adverse Events	The secondary outcome adverse events was defined as any event that occurred during the course of the trial that All adverse events and serious adverse events were recorded on a standardized case report form. Specifically, a stricture in this study was defined a priori as any narrowing of the esophageal lumen in the area of treatment causing symptoms or requiring dilation.	5 year	No
Secondary	Sub-squamous Intestinal Metaplasia	The secondary outcome sub-squamous intestinal metaplasia was defined as prevalence of buried glandular mucosa in the esophagus.	5 year	No