Eradicating Barrett's Esophagus Using Radiofrequency Ablation or a Novel Hybrid Argon Plasma Coagulation Technique (BURN)
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 41
- 试验地点
- 25
- 主要终点
- Rate of stricture-free eradication of dysplastic BE
研究概览
简要总结
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.
详细描述
Barrett's Esophagus (BE) is a pre-malignant condition and may progress to low grade dysplasia, high grade dysplasia and ultimately esophageal adenocarcinoma which has poor prognosis with a 5-year survival rate of only 5 - 20 %. Radiofrequency ablation (RFA) is a standard modality and well-studied endoscopic treatment for dysplastic BE. HybridAPC® (HAPC) is a newer technique for endoscopic treatment of dysplastic BE that involves submucosal fluid injection prior to performing APC. The study aim of this non-inferiority study is to show that HAPC is at least as safe and effective as RFA in the stricture-free eradication of dysplasia (CE-D).
The study is a multi-center, parallel group (HAPC/RFA) prospective, single blind, non-inferiority, randomized controlled study to assess the safety and effectiveness of HAPC (treatment arm) compared to RFA (control arm) in the treatment of BE in up to 144 male and female adult patients. Participants of the study will be enrolled in up to 15 centers in the US. Both techniques have never been directly compared in the treatment of BE.
The specific aim of this non-inferiority study is to show that HAPC is at least as safe and effective as RFA in the stricture-free eradication of dysplasia (CE-D), by inducing complete eradication of dysplasia (CE-D) within 12 months after last treatment as confirmed by endoscopy and histology.
HybridAPC® is an endoscopic technique that is used with the HybridAPC® Probe, the Water Jet Model ERBEJET 2 and an ERBE Argon Plasma Coagulator (APC) Model APC 2/Electrosurgical Unit (ESU) VIO Model System. The Water Jet delivers pressurized sterile 0.9 % sodium chloride solution (normal saline) through the HybridAPC® Probe into the submucosa of the Barrett mucosa. Reduction/limitation of unwanted tissue damage (penetration depth) is being ensured by the saline cushion when applying argon plasma coagulation to ablate Barrett's mucosa with subsequent regeneration of esophageal squamous mucosa.
Radiofrequency ablation (RFA) applied in the control arm using BarrxTM FLEX RFA Generator is an endoscopic technique that delivers high radiofrequency waves using either circumferential (balloon inserted over an endoscopically placed guidewire) device of focal (probe attached to the tip of the endoscope) device to damage the Barrett's mucosa with subsequent regeneration of esophageal squamous mucosa. While a circumferential device can be used to treat larger BE areas, focal device (Halo 60, 90 or through the scope device) can be used to treat small islands of residual BE. The depth of the injury is controlled by regular spacing of the electrodes and the delivery of a pre-set amount of energy through the probes. The PI/Co-investigators will be instructed to operate the BarrxTM FLEX RFA Generator and above referenced catheters according to the cleared labeling.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 86 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Rate of stricture-free eradication of dysplastic BE
时间窗: 12 months
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).
次要结局
- Rate of eradication of intestinal metaplasia (CE-IM)(12 months)
- Cost-effectiveness of HAPC vs. RFA in the treatment of dysplastic BE(12 months)
- Recurrence rate of intestinal metaplasia (CE-IM)(12 months)
- Minor complications(12 months)
- Post-operative pain(7 days)
- Major complications(12 months)
- Recurrence rate of dysplasia (CE-D)(12 months)