Barrett Esophagus
Conditions
Keywords
Barrett's Esophagus, Intestinal Metaplasia, Radiofrequency Ablation
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.
Interventions
DEVICEHALO 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 \*\*\*\*\*\*Phase I was a dosimetry study and Phase II used the preferred dose. The same intervention was used for each dose.
Sponsors
AstraZeneca
Covidien, GI Solutions
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phase I: 6 J/cm^2 The HALO System is an option for eradication of the diseased epithelium of all three subclasses of Barrett's esophagus (non-dysplastic IM, LGD and HGD. The HALO Systems include the circumferential HALO360 Ablation System and the focal HALO90. The Ablation Catheter and Energy Generator work together to deliver energy to the tissue resulting in tissue coagulation. The HALO360 System is designed for longer segment diseased tissue (2 cm or greater) or as an initial treatment to ensure all Barrett's tissue or buried Barrett's glands are eliminated within the zone of intestinal metaplasia. The HALO90 System is designed for short segment Barrett's (2 cm or less) or for follow-up treatment for small Barrett's islands and tongues. In this group, subjects were randomized to the energy density group of 6 J/cm\^2. They received a dose of 6 J/cm\^2 during the course of this study. | 1 |
| Phase I: 8 J/cm^2 The HALO System is an option for eradication of the diseased epithelium of all three subclasses of Barrett's esophagus (non-dysplastic IM, LGD and HGD. The HALO Systems include the circumferential HALO360 Ablation System and the focal HALO90. The Ablation Catheter and Energy Generator work together to deliver energy to the tissue resulting in tissue coagulation. The HALO360 System is designed for longer segment diseased tissue (2 cm or greater) or as an initial treatment to ensure all Barrett's tissue or buried Barrett's glands are eliminated within the zone of intestinal metaplasia. The HALO90 System is designed for short segment Barrett's (2 cm or less) or for follow-up treatment for small Barrett's islands and tongues. In this group, subjects were randomized to the energy density group of 8 J/cm\^2. They received a dose of 8 J/cm\^2 during the course of this study. | 10 |
| Phase I: 10 J/cm^2 The HALO System is an option for eradication of the diseased epithelium of all three subclasses of Barrett's esophagus (non-dysplastic IM, LGD and HGD. The HALO Systems include the circumferential HALO360 Ablation System and the focal HALO90. The Ablation Catheter and Energy Generator work together to deliver energy to the tissue resulting in tissue coagulation. The HALO360 System is designed for longer segment diseased tissue (2 cm or greater) or as an initial treatment to ensure all Barrett's tissue or buried Barrett's glands are eliminated within the zone of intestinal metaplasia. The HALO90 System is designed for short segment Barrett's (2 cm or less) or for follow-up treatment for small Barrett's islands and tongues. In this group, subjects were randomized to the energy density group of 10 J/cm\^2. They received a dose of 10 J/cm\^2 during the course of this study. | 10 |
| Phase I: 12 J/cm^2 The HALO System is an option for eradication of the diseased epithelium of all three subclasses of Barrett's esophagus (non-dysplastic IM, LGD and HGD. The HALO Systems include the circumferential HALO360 Ablation System and the focal HALO90. The Ablation Catheter and Energy Generator work together to deliver energy to the tissue resulting in tissue coagulation. The HALO360 System is designed for longer segment diseased tissue (2 cm or greater) or as an initial treatment to ensure all Barrett's tissue or buried Barrett's glands are eliminated within the zone of intestinal metaplasia. The HALO90 System is designed for short segment Barrett's (2 cm or less) or for follow-up treatment for small Barrett's islands and tongues. In this group, subjects were randomized to the energy density group of 12 J/cm\^2. They received a dose of 12 J/cm\^2 during the course of this study. | 11 |
| Phase II The HALO System is an option for eradication of the diseased epithelium of all three subclasses of Barrett's esophagus (non-dysplastic IM, LGD and HGD. The HALO Systems include the circumferential HALO360 Ablation System and the focal HALO90. The Ablation Catheter and Energy Generator work together to deliver energy to the tissue resulting in tissue coagulation. The HALO360 System is designed for longer segment diseased tissue (2 cm or greater) or as an initial treatment to ensure all Barrett's tissue or buried Barrett's glands are eliminated within the zone of intestinal metaplasia. The HALO90 System is designed for short segment Barrett's (2 cm or less) or for follow-up treatment for small Barrett's islands and tongues. In this group, subjects were randomized to the energy density group of 6 J/cm\^2. All Halo 360 treatments performed at 10 J/cm\^2; All Halo 90 treatments performed at 12 J/cm\^2 | 70 |
| Total | 102 |
Baseline characteristics
| Characteristic | Phase I: 6 J/cm^2 | Phase I: 8 J/cm^2 | Phase I: 10 J/cm^2 | Phase I: 12 J/cm^2 | Phase II | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 2 Participants | 4 Participants | 16 Participants | 22 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 10 Participants | 8 Participants | 7 Participants | 54 Participants | 80 Participants |
| Region of Enrollment Puerto Rico | 0 participants | 0 participants | 0 participants | 0 participants | 18 participants | 18 participants |
| Region of Enrollment United States | 1 participants | 10 participants | 10 participants | 11 participants | 52 participants | 84 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 18 Participants | 21 Participants |
| Sex: Female, Male Male | 1 Participants | 10 Participants | 8 Participants | 10 Participants | 52 Participants | 81 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 1 | 0 / 10 | 0 / 10 | 0 / 11 | 0 / 70 |
| serious Total, serious adverse events | 0 / 1 | 0 / 10 | 0 / 10 | 0 / 11 | 0 / 70 |
Outcome results
Primary
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).
Time frame: 5 year
Population: The analysis was done per protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase I: 6 J/cm^2 | Percentage of Participants With Histological Clearance of Barrett's Metaplasia | 100 Percent of Participants |
| Phase I: 8 J/cm^2 | Percentage of Participants With Histological Clearance of Barrett's Metaplasia | 20 Percent of Participants |
| Phase I: 10 J/cm^2 | Percentage of Participants With Histological Clearance of Barrett's Metaplasia | 78 Percent of Participants |
| Phase I: 12 J/cm^2 | Percentage of Participants With Histological Clearance of Barrett's Metaplasia | 82 Percent of Participants |
| Phase II | Percentage of Participants With Histological Clearance of Barrett's Metaplasia | 92 Percent of Participants |
Secondary
Adverse Events
The secondary outcome adverse events was defined as any event that occurred during the course of the trial
Time frame: 5 year
Population: The analysis was done per protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase I: 6 J/cm^2 | Adverse Events | 0 Participants |
| Phase I: 8 J/cm^2 | Adverse Events | 0 Participants |
| Phase I: 10 J/cm^2 | Adverse Events | 7 Participants |
| Phase I: 12 J/cm^2 | Adverse Events | 0 Participants |
| Phase II | Adverse Events | 28 Participants |
Secondary
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.
Time frame: 5 year
Population: The analysis was done per protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase I: 6 J/cm^2 | Percentage of Participants With Sub-squamous Intestinal Metaplasia | 0 Percent of Participants |
| Phase I: 8 J/cm^2 | Percentage of Participants With Sub-squamous Intestinal Metaplasia | 0 Percent of Participants |
| Phase I: 10 J/cm^2 | Percentage of Participants With Sub-squamous Intestinal Metaplasia | 0 Percent of Participants |
| Phase I: 12 J/cm^2 | Percentage of Participants With Sub-squamous Intestinal Metaplasia | 0 Percent of Participants |
| Phase II | Percentage of Participants With Sub-squamous Intestinal Metaplasia | 0 Percent of Participants |
Secondary
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.
Time frame: 5 year
Population: The analysis was done per protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase I: 6 J/cm^2 | Progression of Histological Grade | 0 Percent of Participants |
| Phase I: 8 J/cm^2 | Progression of Histological Grade | 0 Percent of Participants |
| Phase I: 10 J/cm^2 | Progression of Histological Grade | 0 Percent of Participants |
| Phase I: 12 J/cm^2 | Progression of Histological Grade | 0 Percent of Participants |
| Phase II | Progression of Histological Grade | 0 Percent of Participants |