EndoRotor ablation of Barrett's esophagus: Safety and Feasibility study

Barrett*s metaplasia is a change in the esophageal lining from a squamous to
intestinal type mucosa that increases the risk of the development of esophageal
adenocarcinoma (EAC). Esophageal adenocarcinoma evolves through a multi-step
process, including low-grade dysplasia, high-grade dysplasia and then early
stage esophageal adenocarcinoma. Both stages of dysplasia in Barrett*s
esophagus are currently accepted conditions for pre-emptive treatment by
endoscopic means. Additionally, guidelines advocate ablating residual Barrett*s
metaplasia after complete endoscopic mucosal resection (EMR) of mucosal EAC,
due to the risk of metachronous lesions. The endoscopic removal of Barrett*s
metaplasia without dysplasia is however still debated.

Several techniques have been described for the endoscopic ablation of Barrett*s
metaplasia, which include radiofrequency ablation (RFA), argon plasma
coagulation (APC), photodynamic therapy (PDT), cryotherapy, EMR and surgical
removal of the esophagus. The most commonly used limited-morbidity techniques
are RFA and EMR. RFA involves ablating the abnormal lining using radiofrequency
energy and allowing the area to heal. Although it is relatively fast and easy
to perform, it is expensive (over $2,000 per procedure), it does not harvest
tissue for pathological evaluation, and adverse events such as stricture (5%)
and bleeding (1%) can occur. A majority of patients will experience chest pain
after the procedure which usually lasts a few days, and in 1-2% of patients the
pain is more severe and longer lasting. EMR is a technique that allows the
endoscopist to resect the lesion away from the remainder of the esophagus. EMR
by Cap-technique is a endoscopic technique where a lesion is first lifted by a
submucosal fluid injection after which the lesion is sucked into the cap and
then grasped and ligated by a snare using electrocautery. EMR by multiband
mucosectomy (MBM) uses modified variceal band ligators with a band-and-cut
technique. Although EMR produces samples that can be histologically
interpreted, a stepwise radical endoscopic resection (SRER) of the Barrett*s
mucosa is associated with a high stenosis rate of 48%.

The EndoRotor® is an automated mechanical endoscopic mucosal resection system
for use in the gastrointestinal tract for benign neoplastic or pre-malignant
tissue removal. The EndoRotor® suctions up the tissue and cuts it,
automatically sending the tissue to a collection trap for histological
evaluation. As the system automatically suctions and cuts about 1000 times a
minute, it allows for the rapid and targeted removal of mucosa. The expected
advantages of the EndoRotor® for the ablation of Barrett*s mucosa are 1) it
allows for histological evaluation of the tissue, 2) there is no heat or
cautery artifact in the samples that are collected, 3) it potentially has a
lower stricture risk than SRER due to the absence of electrical ligation
involvement in the procedure, 4) it is 8 to 10 times cheaper than RFA and 5) it
is potentially faster than RFA or EMR.

The EndoRotor® has been used to resect esophageal mucosa in a live porcine
model as part of a Good Lab Practices (GLP) study at CBSET, Lexington,
Massachusetts, USA, as well as for a preliminary research project in Germany at
the Mariensee Animal Facility using live pigs, where the technical properties
and therapeutic potential were evaluated. In September 2015, the EndoRotor®
device acquired the CE-mark for gastroenterological mucosal resections in
humans.

The aim of this study is to assess for the first time in humans, the safety and
feasibility of the EndoRotor® for the ablation of Barrett*s esophagus.

This is a longitudinal prospective study in 30 patients to evaluate safety and
feasibility of the EndoRotor® for the endoscopic ablation of Barrett*s mucosa.
For this safety and feasibility trial a minimum 50% of the esophageal
circumference will be resected per procedure. The 4 participating centers are
expected to enroll a mean number of 3-8 patients during a period of 6 months
and the outcomes will be scored 3 months after the procedure.

Study Visits and Procedure:

Device training:
Prior to execution of the protocol, all investigators shall have become
proficient in the use of the EndoRotor® device, by training in live porcine
models and/or having performed 2-3 ablation procedures in patients with
Barrett*s esophagus.

Pre-EndoRotor® assessment:
Endoscopic assessment including biopsies with low- or high-grade dysplasia
should have been done no longer than 6 months prior to the ablation procedure.
Complete endoscopic mucosal resection of a lesion should be done no shorter
than 6 weeks prior to the ablation procedure, allowing for enough time to heal
the mucosa. The treating physician will assess if the patient fulfills the
inclusion and exclusion criteria, and shall inform the patient about the study.
Only after providing informed consent, the patient will participate in the
study.

EndoRotor® ablation procedure:
All procedures will be performed using high resolution endoscopes with a 3.2mm
size working channel and the through-the-scope EndoRotor® Mucosal Resection
System. The EndoRotor® system will be prepared by attaching the EndoRotor®
catheter, foot pedal and the calibrated suction to the Control Unit, ensuring
there is a filter in the collection unit (specimen trap), and then priming the
catheter with 0.9% normal saline. The full set of instructions for the
EndoRotor® system can be found in the attached Instructions For Use (IFU)
document. The procedures will be performed under sedation. The choice of
sedation (conscious sedation or general anesthesia) will be left to the
discretion of the endoscopist.

The esophagus is first evaluated using white light high-resolution endoscopy
(WLE) and narrow band imaging (NBI). The extent of the Barrett*s segment is
documented according to the Prague C&M classification and by taking still
images with WLE and NBI at 1cm intervals. In the absence of visible lesions,
the patient is eligible for ablation using the EndoRotor® device.

For this safety and feasibility trial at least 50% of the esophageal
circumference will be resected in one procedure. Prior to ablation, submucosal
injection with diluted adrenalin can be performed as to minimize
intra-procedural bleeding. The EndoRotor® catheter will be inserted through the
working channel of the endoscope until it is in proper cutting position with
the cutting surface oriented towards the mucosal lesion and the catheter no
more than 3cm out of the scope. The physician will turn the motor on by
depressing the blue pedal and engage cutting by holding the orange pedal for as
long as he/she wishes to cut tissue. Cutting should be performed while moving
the EndoRotor® catheter over the mucosal area until only submucosa is seen. It
is important to take care to not keep the suction activated when there is no
intention to cut mucosa and when stopped for more than 1 second while apposed
to tissue to not risk creating a perforation. Cutting should be done starting
at the GE-junction and then moving proximally.

After at least 50% of the esophageal circumference has been ablated by the
EndoRotor® system and incidental bleeding has been managed, as is standard of
care, still images with WLE and NBI will be taken at 1cm intervals. This will
provide baseline images to compare with after 3 months follow-up. All relevant
data will be recorded on predefined case record forms during and after the
procedure.

Histopathology examination:
Resected tissue collected in the Specimen Trap will be placed in 10% Formalin
and sent to the pathologist for routine histological evaluation by experienced
GI pathologists.

Medication and discharge regime
All patients will be on a maintenance dose of a proton pump inhibitor (by
preference Esomeprazole) at a dosage of 40mg twice a day during the whole
treatment period until follow-up. Additionally, during the first 14 days post
procedure, Sucralfate suspension 4 times daily (after each meal and prior to
bedtime) and Ranitidine 300mg at bedtime will be prescribed, as is routinely
done after all ablative procedures. In case of pain, patients may take
paracetamol 1000mg maximum 4 times daily.
In the first 24 hours post ablation, patients will be restricted to drinking
clear liquids only. After 24 hours, they will be allowed a normal diet.
Patients will be asked to complete a short 30 - day diary in which symptoms
such as dysphasia, discomfort and pain will be recorded. If after 3 days the
patient is free of complaints, they can stop completing the questionnaire.

Follow-up
At 12 weeks follow-up, the first post treatment endoscopy will be performed.
Still images with WLE and NBI will be taken at 1cm intervals to assess the
percentage of endoscopically visible surface regression of the resected
Barrett*s area. During the 12 weeks follow-up, all unscheduled visits,
unscheduled endoscopies and complications will be recorded. After the first
post treatment endoscopy, further treatment and follow-up will be performed
according to the standard guidelines.

An independent safety committee will evaluate all treated cases after the first
5 procedures, and will again review after 10 and 20 cases.

EndoRotor ablation to eradicate Barrett's mucosa

The burden of participation is low since patients with Barrett*s esophagus with
high-grade dysplasia, low-grade dysplasia or residual Barrett*s after complete
endoscopic resection of esophageal adenocarcinoma by EMR will already be
undergoing upper endoscopy with endoscopic ablation in routine clinical
practice. There is a small but increased risk of complications as a result of
endoscopic resection with the EndoRotor® (bleeding, perforation, pain and
post-procedural stenosis), but these complications can usually be managed by
endoscopic means. These complications are however also seen with the current
standard of care (radiofrequency ablation and EMR).
From the patient*s point-of-view, participation in the study will require their
consent and a post-procedural assessment on pain and discomfort, by filling out
a 30-day diary. The initial endoscopic procedure for treatment and the 3-month
follow-up endoscopy are part of routine practice. There is no financial burden
or incentive for patients to participate in this study.