Self-sizing Radiofrequency ablation balloon for eradication of Barrett's esophagus: a randomized trial comparing two different treatment regimens

Radiofrequency ablation is an established endoscopic technique for eradication
of Barrett*s esophagus which has been investigated in a variety of study
designs (including two randomized trials), and settings (US and EU, tertiary
academic centers, community referral
centers).
Radiofrequency ablation is
associated with an acceptable safety profile, high rates of complete
eradication of dysplasia and intestinal metaplasia, durability of effect, and a
significant relative risk reduction for neoplastic progression. As a result,
radiofrequency ablation is considered standard of care for patients with
high-grade dysplasia, as well as for residual Barrett tissue after endoscopic
resection of early cancer.
Currently, most patients undergo primary circumferential ablation with a
balloon based electrode, the Barrx360 System, followed by additional focal
ablation using a cap-based electrode, the Barrx90 System. The Barrx360
procedure starts with the introduction of a sizing balloon to measure the
internal esophageal diameter, because the ablation balloon comes in different
sizes (18-31mm). The sizing balloon is used to take multiple measurements of
the esophageal diameter and assists the endoscopist in choosing an ablation
catheter with the appropriate diameter. Subsequently, the sizing balloon is
removed and the BE segment can be treated with the ablation balloon. The
advised standard treatment regimen for Barrx360 procedures consists of two
ablation runs with extensive cleaning of the ablation zone after the first
ablation (1x-clean-1x). The entire treatment procedure is time-consuming, as it
consists of many different steps and requires multiple introductions and
removals of the endoscope, sizing catheters and ablation balloons which are
impractical and uncomfortable to the patient.
By incorporating the sizing balloon and the Barrx360 ablation balloon into a
single device, the use of a separate sizing balloon and the need for having
multiple sized balloon catheters are eliminated. The new Self Sizing RFA
balloon catheter is a circumferential balloon catheter, and consists of a 4cm
long bipolar electrode that is furled around a balloon. This single balloon
catheter can unfurl in size ranges including 18-31mm, making it possible to
size and treat the BE segment in a single step. Secondly, if the simplified
ablation regimen (in which one ablation will be applied and the cleaning step
is omitted) proves equally effective to the standard ablation regimen when
using the Self Sizing balloon, the entire circumferential ablation procedure
can be vastly improved (less time consuming and more comfortable for the
patient).

The current study is designed to determine the most optimal treatment regimen
for Barrett*s esophagus with early neoplasia, using the Self Sizing RFA
balloon. In this study we will compare the standard ablation regimen
(1x-clean-1x) with a simplified regimen (1x-no clean)

If a patient is eligible for the study after one mapping endoscopy, and/or
after endoscopic resection, and no abnormalities (visible lesions and/or severe
stenosis) are observed during the endoscopy, the patient will undergo
randomization.
Patients are randomly assigned to treatment with the standard protocol, the
simple double ablation protocol or the simple single ablation protocol, using
the Self Sizing RFA balloon catheter. Randomization is performed according to a
computer-generated randomization sequence which is concealed from the
researchers. Randomization is stratified according to prior endoscopic
resection.
Randomization of eligible patients is performed on-site by the study
coordinator during the endoscopic procedure after eligibility of the patient is
confirmed. The study coordinator enrolls participants and assigns them to the
standard or one of the simple protocols by using the ALEA software.

Endoscopic resection at baseline
For patients with a visible abnormality mandatory endoscopic resection is
performed. In case there is no suspicion on submucosal infiltration of the
lesion the choice of ER technique will be left to the discretion of the
endoscopist, with a preference for the ER-cap technique or endoscopic
submucosal dissection (ESD) for elevated or depressed visible abnormalities and
the multi-band mucosectomy (MBM) technique for flat type mucosal abnormalities.
In case of suspicion on submucosal infiltration, the resection is preferably
performed using the ER-cap or the ESD technique, since this will result in a
larger and deeper resection specimen than with the MBM technique.
Prior to the ER procedure, the extent of columnar lined esophagus is documented
according to the Prague C&M classification.
During the ER procedure, biopsies from the remaining Barrett*s segment (4Q/2cm)
will be obtained immediately after the endoscopic resection, to evaluate the
histological status of the remaining mucosa and to exclude the presence of
cancer. Patients who show residual invasive cancer in these biopsies are not
eligible for RFA.

Ablation procedure
Inspection of the Barrett*s segment and randomization.
The esophagus is evaluated using white light high-resolution endoscopy (WLE)
and narrow band imaging (NBI). The extent of columnar lined esophagus is
documented according to the Prague C&M classification and by taking still
images with WLE+NBI at 1 cm intervals. In the absence of visible abnormalities
and no severe stenosis, patients are subsequently randomized to circumferential
ablation with the Self Sizing RFA balloon using the two simplified regimen or
the standard ablation regimen.

Standard ablation regimen:
After mapping and randomization, the Barrett*s segment is flushed with the
mucolytic agent acetylcysteine (1%) followed by flushing with tap water. The
Self Sizing RFA balloon (GI Solutions Covidien, Sunnyvale, CA) is then
introduced and positioned at the desired treatment zone. The device is
inflated, and the electrode unfurls until the electrode contacts the esophageal
wall. Under visual control the BE is ablated (10 J/cm2 at 300 Watt) working
proximal to distal using visual repositioning. A small overlap (i.e. <1cm)
between ablation zones is allowed. After the first ablation pass, the endoscope
is removed followed by removal of the ablation catheter. The coagulum is
cleaned off the balloon catheter. The endoscope is reintroduced to irrigate and
suction the ablation zone. A distal attachment cap may be attached to the tip
of the endoscope to gently wipe of the coagulum from the ablated segment. After
irrigating and suctioning the debris away as much as possible, the ablation
zone is cleaned by forcefully flushing water through a spraying catheter. The
stomach is emptied and deflated, the endoscope is removed and the ablation
catheter is reintroduced to repeat the ablation. After this second ablation no
additional cleaning of the ablation zone is required. First, the endoscope is
removed, followed by careful removal of the ablation catheter.

Simplified single ablation regimen:
The Barrett segment will be cleaned with water through the waterjet channel of
the endoscope. Flushing with the mucolytic agent acetylcysteine (1%) is not
performed. The Self Sizing RFA balloon (GI Solutions Covidien, Sunnyvale, CA)
is then introduced and positioned at the desired treatment zone. The device is
inflated, and the electrode unfurls until the electrode contacts the esophageal
wall. Under visual control the BE is ablated (10 J/cm2 at 300 Watt) once. After
deflation, the balloon is advanced distally to ablate subsequent zones with a
single ablation in an identical way. There is no cleaning step.

Medication and discharge regimen
All patients will be on a maintenance dose of a proton pump inhibitor (by
preference esomeprazole) at a dosage of 40 mg twice a day during the whole
treatment period and follow-up. This medication is supplemented with ranitidine
300 mg at bedtime and sucralfate suspension three times a day (after each meal
and prior to bedtime) for a period of two weeks following all RFA procedures.
Further treatment and follow-up
At 3 months, the first post-treatment endoscopy will be performed with white
light high-resolution endoscopy (WLE) and NBI. Still images with WLE+NBI will
be obtained at 1-cm intervals throughout the extent of the original Barrett*s
segment, to assess the percentage of endoscopically visible surface regression
of BE. Further treatment and follow-up are performed according to standard
guidelines. Repeat RFA treatment will be performed at 2-3 months intervals with
a maximum of two Barrx360 and three Barrx90 ablation sessions. For all
patients, at least one Barrx90 ablation will be performed for circumferential
ablation of the squamocolumnar junction.
After complete removal of BE is achieved, patients will be scheduled for
surveillance endoscopy after six months, twelve months and annually thereafter
with WLE plus NBI and 4-quadrant biopsies from the gastric cardia (immediately
below the neosquamocolumnar junction).

Radiofrequency ablation to eradicate Barrett's mucosa

The ablation procedure with the self-sizing balloon will be less complicated,
because sizing of the inner esophagus will not be performed as done in the RFA
procedure according the general guidelines. Less number of introductions of the
gastroscope are needed and the procedure time will shorten. During the
procedure with self-sizing balloon accurate imaging before and after the
ablation will increase the procedure. The two simple regimens will be even
shorter than the standard procedure with the self-sizing balloon. The balloon
and endoscope will only be introduced once instead of twice.
We expect no additional risk for patients participating in the study than for
patients undergoing the regular ablation.
Study patients will be asked to fill out a diary for the first 30 days after
the RFA treatment. The diary consists of a list with pain symtoms.