Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05829447 |
| Other study ID # |
Valduce Hospital |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
May 1, 2023 |
| Est. completion date |
December 1, 2023 |
Study information
| Verified date |
March 2024 |
| Source |
Valduce Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The present trial is aimed at evaluating whether in individuals scheduled for colonoscopy in
the framework of a structured FIT (Fecal Immunochemical stool test)-based colorectal cancer
screening program, the combination of an AI (artificial intelligence) system (CADEYE) with a
mucosal exposure device (G-EYE 760R endoscope) increases the identification of subjects at
high risk to develop colorectal cancer (according to recent ESGE-European Society of
Gastrointestinal Endoscopy guidelines subjects are labelled as "high-risk" if harboring at
least 1 adenoma ≥ 10 mm or with high grade dysplasia, or ≥ 5 adenomas, or any serrated polyp
≥ 10 mm or with dysplasia) when compared to colonoscopy performed with the support of AI
only.
Individuals fulfilling inclusion criteria are randomized (1:1) to two different arms (Control
arm and Interventional arm, see below). Randomization is based on a computer-generated
randomized block sequence, stratified according to age (50-61 vs. 62-74) and gender (male vs.
female); size of the blocks (10 individuals) is not communicated to the investigator.
Allocation is concealed and kept in a sealed envelope, which is opened just before starting
colonoscopy.
Individuals randomized in the Intervention arm receive colonoscopy examination with G-EYE
760R colonoscopes; once the cecum is reached the balloon is inflated, and the endoscope is
withdrawn with the inflated balloon; the colonoscopy is performed with the support of the
CADEYE system for polyp detection in both insertion and withdrawal phase; all polyps
identified are removed and sent for histopathology examination.
Individuals randomized in the Control arm (CADEYE only) receive colonoscopy with G-EYE 760R
colonoscope but the balloon remains deflated for the entire procedure; the colonoscopy is
performed with the support of the CADEYE system for polyp detection in both insertion and
withdrawal phase; all polyps identified are removed and sent for histopathology examination.
The main outcome measure is the rate of "high risk" individuals across the two study arms.
Description:
The Italian Colorectal Cancer (CRC) screening program invites the resident population aged
50-74 years for Fecal Immunochemical Test (FIT) every 2 years. Subjects who test positive are
referred for colonoscopy. Colonoscopy and polypectomy prevent incident cases of colorectal
cancer by their detection at an early and curable stage, and by identification and removal of
colorectal precancerous lesions (i.e. adenomas). Taking into account the number and the
histological features of polyps identified, colonoscopy also allows to stratify individuals
according to the risk of developing colorectal cancer over time (low-risk vs. high-risk
subjects), thus allowing to plan a balanced risk-based follow-up schedule: high-risk
individuals are scheduled for a surveillance colonoscopy in 3 years, whereas low-risk
individuals are scheduled for a further FIT test in five years or for a new colonoscopy in 10
years. However, colonoscopy is far from being a flawless tool. Studies that have measured the
incidence of colorectal cancer diagnosed in subjects who have recently undergone colonoscopy
with negative results (the so-called interval cancers) have shown that a significant portion
of interval cancers is related to pre-neoplastic, or frankly neoplastic colonic lesions,
missed during the endoscopic procedure.
In the last few years, it has been shown that in patients undergoing colonoscopy for mixed
indications AI-based systems can effectively support the endoscopist by decreasing the
adenoma miss rate and by increasing the identification of colonic polyps, thus potentially
lowering the rate of interval cancer and increasing the rate of individuals scheduled for a
short follow-up. A recent study demonstrated that AI-assisted colonoscopy is effective also
in the framework of a FIT-based organized CRC screening program resulting in an absolute
difference of 8.3% and 0.23 for adenoma detection rate (ADR) and for adenomas per colonoscopy
(APC), when compared to standard colonoscopy performed without the assistance of AI.
Nevertheless, tandem studies have shown that despite the use of AI systems the miss rate of
colonic adenomas is still about 15-20%. In fact, AI systems only allow to highlight polyps
that are framed by the endoscopist within the screen. Therefore, the use of computerized
AI-based system cannot disregard an accurate retraction technique, focused on exploring in an
extensive and effective way the space between the folds. Several tools, mostly consisting of
distal attachments or plastic caps, aimed at facilitating the evaluation of the space between
the folds favoring their smoothing during the endoscope withdrawal, have been developed to
maximize mucosal exposure. Among them, the G-EYE system includes a balloon integrated at the
distal tip of a standard colonoscope, which flattens haustral folds, centralizes the
colonoscope's optics, and reduces bowel slippage during endoscope withdrawal. Initial studies
showed that G-EYE balloon system, when compared with standard colonoscopy, increases not only
adenoma detection rate but also the detection of advanced, flat, and sessile serrated
adenomas/polyps. Recently, a new user friendly G-EYE balloon system (G-EYE 760R endoscope)
has been marketed: it consists of a standard last-generation colonoscope with a permanently
integrated balloon, placed at the bending section of the endoscope, which can be gradually
insufflated on-demand by the endoscopist through a pedal control. It can be hypothesized that
the combination of AI systems with mucosal exposure devices might further decrease the polyp
miss rate, by maximizing the detection of adenomas. Moreover, initial studies based on such a
strategy, combining AI with mucosal exposure devices, yielded encouraging results. However,
the combination of CADEYE with G-EYE 760R endoscopes has not been evaluated so far.
The present prospective randomized controlled trial is aimed at evaluating whether in
individuals scheduled for colonoscopy in the framework of a structured FIT-based colorectal
cancer screening program, the combination of an AI system (CADEYE) with a mucosal exposure
device (G-EYE 760R endoscope) increases the identification of subjects at high risk to
develop colorectal cancer, when compared to colonoscopy performed with the support of AI
only. In addition, it will be also evaluated whether the use of an AI system combined with a
mucosal exposure device, increases:
- the adenoma detection rate (i.e. the rate of individuals with at least one
histologically confirmed adenoma)
- the number of adenomas per colonoscopy (i.e. the number of adenomas detected divided by
the number of all colonoscopies performed)
- the serrated lesions with neoplastic potential (sessile serrated lesions-SSA;
traditional serrated adenomas - TSA) detection rate.
- the detection rate of right colon adenomas
- the detection rate on non-polypoid colonic lesions. Individuals fulfilling the inclusion
criteria are randomized (1:1) in two arms (see below). Randomization is based on a
computer-generated randomized blocks sequence, stratified according to age (50-61 vs.
62-74) and gender (male vs. female); size of the blocks (10 individuals) is not
communicated to the investigator. Allocation is concealed and kept in a sealed envelope,
which is opened just before starting the procedure.
Randomization groups:
- Group A (CADEYE only): all subjects receive colonoscopy with G-EYE 760R colonoscope but
the balloon remains deflated for the entire procedure; the colonoscopy is performed with
the support of the CADEYE system for polyp detection in both insertion and withdrawal
phase; all polyps identified are removed and sent for histopathology examination.
- Group B (CADEYE+G-EYE 760R): all individuals receive colonoscopy examination with G-EYE
760R colonoscopes; once the cecum is reached the balloon is inflated, and the endoscope
is withdrawn with the inflated balloon; the colonoscopy is performed with the support of
the CADEYE system for polyp detection in both insertion and withdrawal phase; all polyps
identified are removed and sent for histopathology examination.
For the present study a clinical outcome measure, such as the rate of "high risk" individuals
across the two study arms, is calculated and compared. According to recent European Society
of Gastrointestinal Endoscopy (ESGE) guidelines subjects are labelled as "high-risk" if
harboring at least 1 adenoma ≥ 10 mm or with high grade dysplasia, or ≥ 5 adenomas, or any
serrated polyp ≥ 10 mm or with dysplasia.
All endoscopic procedures are performed using the ELUXEOTM 7000 endoscopy platform (including
videoprocessor ELUXEO TM VP-7000 and light source ELUXEO TM BL-7000; Fujifilm Co., Tokyo,
Japan), high-definition 26''monitors (Barco NV, Kortijk, Belgium) and G-EYE 760R endoscopes
(Fujifilm Co., Tokyo, Japan).
Bowel preparation is a split regimen of low-volume solution, according to local protocol.
Quality of bowel cleansing is recorded by using the Boston Bowel Preparation Scale.
Colonoscopies are performed under conscious sedation with carbon dioxide insufflation.
Intubation time, overall withdrawal time, intervention time and inspection time during
withdrawal are measured using a stopwatch. An inspection time of at least 6 minutes (2
minutes in each colonic segment, namely right, transverse and left colon) is mandatory in
both study arms. The mucosa is carefully inspected, and all polyps are classified according
to their location, size, and morphology (according to Paris classification). The
pathologist's measure, when available, is considered the reference standard; the
endoscopist's measure estimation is used in the remaining cases (i.e., piecemeal resection).
Polyp location is defined as "proximal" if proximal to the splenic flexure). All identified
polyps are removed (biopsy for non-resectable lesions), irrespective of size, color or
subjective interpretation, with the possible exception of very small (1-5 mm)
hyperplastic-appearing polyps located in the rectum and-according to the judgment of the
endoscopists-not clinically significant.
All participating endoscopists have credentials for participating in the organized FIT-based
screening program (more than 300 colonoscopies/year; cecal intubation rate >95%, adenoma
detection rate>25%). All endoscopist are familiar with CADEYE features and use this system on
a regular basis. All participating endoscopists receive a formal training (a 20' lecture
focused on the use of the G-EYE 760R endoscope). All of them performed at least 10
colonoscopies with the G-EYE 760R endoscope, to become acquainted with the system, before
entering the study.
All resected or biopsy specimens are fixed in 10% buffered formalin solution sent to
pathology in separate jars. They are processed and stained for histopathology using standard
methods and evaluated by expert pathologists (one in each center), with credentials to
participate in the FIT-based organized screening program; pathologists are blinded to the
assigned examination mode. All lesions are classified according to Vienna classification. An
advanced adenoma is defined as an adenoma ≥10 mm and/or with villous component >20%, and/or
high-grade dysplasia.
