Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT03621319 |
| Other study ID # |
2015_1 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
July 24, 2019 |
| Est. completion date |
May 5, 2021 |
Study information
| Verified date |
July 2021 |
| Source |
Erbe Elektromedizin GmbH |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
Description:
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.
Patients with dysplastic BE will be identified at each participating center, and defined as
those with LGD within previous 6 months and HGD/cancer within previous 6 months, both timed
from date of consent. All histology slides from biopsies and endoscopic mucosal resection
(EMR) specimens will be read by the local pathologist for patient management purposes and
separately by a single independent reference pathologist to confirm patient eligibility for
randomization.
Eligible patients will be block randomized at each participating study center at a ratio of 1
: 1 to receive treatment of dysplasia with HAPC or RFA after EMR of visible lesions (if
present) has been performed as per standard of care. All patients will be assigned a unique
registration number allocated by the Electronic Data Capture (EDC) system following details
submitted on a web form. Due to the nature of the intervention only the patient will be
blinded (single blinding), and not the PI or Co-investigators. The assigned HAPC ablation or
RFA procedure will be performed at 8 to 12-week intervals until eradication of BE has been
achieved. A maximum number of 4 treatment sessions is allowed.
Once the BE has been eradicated endoscopically, 4 quadrant biopsies every 1-2 cm will be
performed to confirm complete eradication of dysplasia/IM (standard of care) and slides sent
for confirmation by the central pathologist.
Primary statistical analysis will compare the proportions of patients in whom stricture-free
eradication of dysplastic BE has been achieved.
As secondary endpoints complete endoscopic and histological eradication of intestinal
metaplasia (CE-IM), stricture rate, post-operative pain, cost-effectiveness and recurrence of
intestinal metaplasia and dysplasia will be documented and reported. No formal tests of
hypothesis will be applied for these secondary endpoints.
Data from the trial will be entered into a database (VISION EDC, version 8, Prelude Dynamics,
Austin, TX) and all statistical analyses will be performed using validated software (SAS,
version 9.4; IBM/SPSS, version 23; Cytel StatXact, version 11; or R).
