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

NCT03621319 | Terminated DMC FDA Device

• 1 other identifier: 2015_1
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 13

Brief Summary

Lay summary: Barrett's Esophagus (BE) involves a change of the esophagus lining (BE epithelium) which in a small proportion of patients could be the starting point for the development of cancer (esophageal adenocarcinoma). Currently, there is evidence that this change is initiated by acid reflux from the stomach which then could progress in a stepwise manner from the healthy epithelium to cellular changes (intestinal metaplasia, low-grade and high-grade dysplasia) and finally to adenocarcinoma. Surgery is considered the standard therapy for this cancer which involves the risk of death and complications with quality of life impairments. New possibilities for treatment have evolved with endoscopic therapies which allow for treatment of early changes of the epithelium (intestinal metaplasia and dysplasia) prior to the occurrence of cancer using either argon plasma coagulation (APC) or radiofrequency ablation (RFA). Both are established methods for eradication of BE by thermal ablation of the BE epithelium using high frequency current (HF). More advanced BE epithelium with early visible cancers are being treated by endoscopic mucosal resection (EMR). After EMR the residual Barrett's epithelium can also be removed by ablation with RFA or APC. Currently radiofrequency ablation (RFA) has been suggested as the standard therapy for BE treatment. Although effective in the eradication of the BE epithelium after RFA treatment the re-appearance of BE epithelium and the occurrence of complications such as strictures causing swallowing impairments for food have also been observed in clinical studies. A recently developed method is Hybrid argon plasma coagulation (ablation) \[HybridAPC® (HAPC)\] which combines argon plasma coagulation (APC) with a fluid injection function by a water beam. The water beam allows to establish a fluid cushion (normal sterile saline) right beneath the BE-epithelium prior to thermal ablation thereby protecting the esophagus wall from heat during ablation of epithelium with APC. The goal of this randomized controlled study is to investigate if HAPC is non-inferior to RFA in the stricture-free eradication of the dysplastic BE epithelium.

Conditions

Barrett's Esophagus; High-grade Dysplasia in Barrett Esophagus; Low Grade Dysplasia in Barrett Esophagus

Keywords

Hybrid argon plasma coagulation; Submucosal injection

Outcome Measures

Primary Outcomes (1)

• Rate of stricture-free eradication of dysplastic BE

  Freedom from strictures and complete eradication of dysplasia (CE-D) within 12 months after the last treatment will be measured as a composite safety and effectiveness endpoint. The composite endpoint evaluation is a traditional responder analysis with a single measure. The composite endpoint will have two possible outcome responses for each study subject: success or failure. The study or control treatment will be considered a success for a study subject only if both conditions are met: freedom from strictures and complete eradication of dysplasia. The number of successes and failures allows the estimation of success rates in the two study arms. These rates will be compared using standard statistical methods for rates (that is, binomial proportions).

  12 months

Secondary Outcomes (7)

• Rate of eradication of intestinal metaplasia (CE-IM)

  12 months

• Post-operative pain

  7 days

• Major complications

  12 months

• Minor complications

  12 months

• Recurrence rate of dysplasia (CE-D)

  12 months

Study Arms (2)

Hybrid argon plasma ablation (HAPC)

ACTIVE COMPARATOR

Eligible participants will be randomized to receive ablation of dysplasia with Hybrid argon plasma coagulation (HAPC) after EMR of visible lesions (if present) has been performed as per standard of care.

Device: Hybrid argon plasma ablation (HAPC)

Radiofrequency ablation (RFA)

ACTIVE COMPARATOR

Eligible participants will be randomized to receive treatment of dysplasia with RFA after EMR of visible lesions (if present) has been performed as per standard of care.

Device: Radiofrequency ablation (RFA)

Interventions

Hybrid argon plasma ablation (HAPC) DEVICE

-The assigned HAPC ablation will be performed at 8 to 12 week intervals until eradication of BE has been achieved or a total of 4 treatments have been performed

Hybrid argon plasma ablation (HAPC)

Radiofrequency ablation (RFA) DEVICE

-The assigned RFA procedure will be performed at 8 to 12 week intervals until eradication of BE has been achieved or a total of 4 treatments have been performed

Radiofrequency ablation (RFA)

Eligibility Criteria

• Age: 18 Years - 86 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age of 18-85 years (inclusive)
• Dysplastic BE, confirmed by the central pathologist; specifically:
• Low grade dysplasia documented on biopsy within 6 months of consent date or
• High grade dysplasia documented on biopsy within 6 months of consent date
• Barrett's extent of: C/M≥1 cm and C/M ≤ 6 cm using the Prague criteria \[C = circumferential extent of disease / M = maximum extent of disease\]
• Ability to provide written and informed consent

You may not qualify if:

• Barrett's extent of: C/M \<1 cm or a C/M-value \> 6 cm using the Prague criteria
• Prior EMR (endoscopic mucosal resection) for G3/G4; L1; V1; R1 (vertical margin only) or submucosal invasion;
• Presence of endoscopically visible abnormalities at the time of initial study treatment with HAPC or RFA. These participants can undergo EMR and then continue in the trial after a suitable healing period, provided randomization can occur within 90 days of consent.
• Presence of invasive cancer on biopsy
• Known pregnancy or plans to become pregnant
• Complete eradication is not considered a relevant treatment goal or in whom additional treatment is contraindicated;
• pre-existing significant esophageal pain or dysphagia;
• BE \>80% has been resected by EMR;
• incomplete wound healing 3 months post-EMR despite adequate PPImedication;
• Prior ablative therapy in the esophagus but prior EMR allowed
• Active esophagitis or stricture precluding passage of scope
• Presence of esophageal varices
• Anticoagulant therapy (apart from aspirin or NSAIDS) that cannot be discontinued prior to therapy or uncorrectable hemostatic disorders
• Life expectancy less than 2 years
• Previous gastrectomy or other gastric surgery other than uncomplicated fundoplication

Sponsors & Collaborators

• Erbe Elektromedizin GmbH: lead
• Erbe USA Incorporated: collaborator
• Kansas City Veteran Affairs Medical Center: collaborator
• NAMSA: collaborator

Study Sites (13)

Mayo Clinic Arizona

Scottsdale, Arizona, 85259, United States

Location

University of California

Irvine, California, 92868, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

University of Chicago

Chicago, Illinois, 60687, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Kansas City Veterans Affairs Hospital

Kansas City, Missouri, 64128, United States

Location

Washington University, School of Medicine; Department of Internal Medicine; Division of Gastroenterology

St Louis, Missouri, 63110, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03766, United States

Location

Long Island Jewish Medical Center

New Hyde Park, New York, 11030, United States

Location

Columbia University Medical Center; Division of Digestive and Liver Diseases

New York, New York, 10032, United States

Location

Penn State Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

University of Utah School of Medicine

Salt Lake City, Utah, 84132, United States

Location

MeSH Terms

Conditions

Barrett Esophagus

Interventions

Radiofrequency Ablation

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Radiofrequency Therapy; Therapeutics; Ablation Techniques; Surgical Procedures, Operative

Study Officials

• Prateek Sharma, MD

  Kansas City Veterans Affairs Medical

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2018
• First Posted: August 8, 2018
• Study Start: July 24, 2019
• Primary Completion: May 5, 2021
• Study Completion: May 5, 2021
• Last Updated: July 6, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (13)