Trial Title:
Laser Speckle Contrast Imaging, Surgical Eye & ICG Fluorescence Imaging for Perfusion Assessment of the Gastric Conduit
NCT ID:
NCT05685862
Condition:
Oesophageal Cancer
Conditions: Keywords:
Laser Speckle Contrast Imaging
LSCI
gastric conduit
oesophageal cancer
ICG
fluorescence
Study type:
Observational
Overall status:
Recruiting
Study design:
Time perspective:
Prospective
Intervention:
Intervention type:
Device
Intervention name:
Laser Speckle Contrast Imaging using the PerfusiX-Imaging device
Description:
Patient will undergo the standard-of-care gastric conduit procedure and in addition,
peroperative Laser Speckle Contrast Imaging of the gastric conduit and eosophagus will be
performed.
Arm group label:
Group 1
Summary:
Rationale Globally, esophageal cancer is the seventh most common cancer type, with over
half a million cases reported in 2020. The survival of gastroesophageal cancer is poor
and the prognosis is primarily determined by the possibilities for curative treatment.
After resection of part of the esophagus and cardia, the reconstruction of the esophagus
is performed with a gastric conduit where an anastomosis is made with the proximal
esophageal stump. Globally, a Minimally invasive Esophagectomy (MIE) has a high morbidity
rate and a mortality rate ranging up to 5% as a result of the procedure. One of the most
feared complications is an anastomotic leakage (AL) with a rate of around 12.5% and a
mortality rate of around 15%. AL is associated with prolonged hospital stay and increased
re-operation rates. It is generally accepted that impaired blood flow of the gastric
conduit is the most important cause of AL. The surgical procedure of an esophagectomy and
reconstruction inherently compromises the blood supply of the gastric conduit. However
other than the surgical eye, there is no gold standard in assessing this. Surgeons
generally look for traditional indicators of tissue viability such as pulsating vessels,
bleeding of the resected edges, tissue color and intestinal motility. However, an
objective indication of the tissue perfusion is still lacking, implying the clinical need
for one.
Objectives In this trial the investigators will study the utility of PerfusiX-Imaging for
perfusion assessment of the gastric conduit in comparison with the standard of care.
Study design The current study is a prospective, observational single-center study in the
Medical Center Leeuwarden.
Study population A total of 30 patients undergoing an esophageal resection will be
included. Patient related study procedures All patients will undergo the standard-of-care
program which includes perfusion assessment by the surgical eye and ICG-fluorescence
imaging. In addition to this standard-of-care, 2D-perfusion maps will be generated from
images taken with PerfusiX-Imaging (LIMIS Development BV, Leeuwarden, The Netherlands) in
combination with a standard surgical laparoscope. Not related to the patient, the
PerfusiX-Imaging images will be shown to the surgeon postoperatively and peroperative
questionnaires will be filled regarding the standard-of-care perfusion assessment.
Study parameters/endpoints Due to the explorative character of this study, there is no
formal hierarchy in the respective endpoints of this study. In this, all endpoints will
add to the overall assessment of the feasibility of the PerfusiX-imaging derived visual
feedback. The investigators will look at the percentage of operating surgeons that
indicated no change in location of the anastomosis or operating plan based on the
additional PerfusiX-Imaging. The percentage of the non-involved surgeons that indicated
no change in location of the anastomosis or operating plan based on the additional
PerfusiX-Imaging. And the homogeneity of the change in location between non-involved
surgeons for individual patients will be analyzed in order to get a sense for the
subjectivity of the interpretation of the images.
The investigators will also compare the additional PerfusiX-Imaging derived visual
feedback to the standard of care by looking at the homogeneity in location of the
watershed area between PerfusiX-Imaging, ICG-fluorescence and based on visual assessment
by the surgical eye. The difference in the location of watershed area between
PerfusiX-Imaging and ICG-fluorescence or based on visual assessment.
In order to get a sense of the scale of the indicated change in location of the
anastomosis the investigators will look at the estimated change in location of the
anastomosis of the gastric conduit/ the esophageal stump in centimeters by the operating
surgeon. The estimated change in location of the anastomosis of the gastric conduit/ the
esophageal stump in centimeters by non-involved surgeons. Lastly, the investigators will
compare the change in the location of the anastomosis by non-involved surgeons in
comparison to the operating surgeon; Burden, risk and benefit to participation Burden Not
applicable. Risks Not applicable. Benefit Not applicable.
Detailed description:
1. INTRODUCTION AND RATIONALE 1.2 Perfusion defects associated with anastomotic leakage
It is generally accepted that impaired blood flow of the gastric conduit is the most
important cause of AL. The surgical procedure of an esophagectomy and reconstruction
inherently compromises the blood supply of the gastric conduit. This is mainly due
to the fact that the blood supply of the gastric conduit is solely dependent on the
right gastroepiploic artery. Good condition and length of this artery and the
microvasculature of the gastric wall is thus of utmost importance. Unfortunately,
the cardiovascular condition of the patient is affected by many uncontrollable risk
factors such as diabetes, smoking, hypertension but also neo-adjuvant
chemoradiotherapy. Surgeons are well aware of the risks of poor perfusion of the
gastric conduit, and the subsequent AL. However other than the clinical experience /
surgical eye, there is no validated method for assessing this. Surgeons generally
look for traditional indicators of tissue viability such as pulsating vessels,
bleeding of the resected edges, tissue color and intestinal motility. However, an
objective estimation of the tissue perfusion is still lacking, implying the clinical
need for one. In this study the investigators will study the utility of laser
speckle contrast imaging (LSCI) for this purpose. The results will be compared to
the current standard-of-care; indocyanine green (ICG) imaging and the surgical eye.
1.3 Laser speckle contrast imaging About the perfusion imaging technique; LSCI. The
first biomedical application of LSCI was reported in the 1981 by Fercher and Biers.
The proposed technique from Fercher and Briers was non-real-time and had its
practical limitations due to the use of non-digital systems which impeded the
clinical use. The first real speed increase to quasi real-time image acquisition and
processing happened in the nineties with the introduction of digital photography.
Generally, the components required are a low-powered laser diode, a diffuser, a
digital camera and processing software (Figure 1). Other names for the same
principle as LSCI are laser speckle imaging (LSI), laser speckle perfusion imaging
(LSPI) and laser speckle contrast analysis (LASCA) as it was named by the first
users.
1.4 The basic principle of laser speckle contrast imaging Speckle patterns are the
random interference patterns that arise when coherent light is backscattered by a
scattering medium such as biological tissue. The slightly different optical
pathlengths cause the waves to reach the observer at random mutual phases, resulting
in bright and dark spots respectively9. The speckle image is built up of static and
dynamic speckles. Static speckles are speckles that do not change over time whereas
dynamic speckles do change over time due to the optical Doppler effect. The dynamic
speckles contain information about movement of the object, or motion of particles
within the object.
In order to be able to detect a change in the speckle pattern, the exposure time of
the camera must be of the order of the speckle decorrelation time, causing a
blurring of the recorded speckle pattern. It is this blurring that is used to
calculate the speckle contrast K using the following formula 1.
K=σ/() (1) Where σ is the standard deviation of the intensity I over the mean
intensity calculated over a window in space or time. Spatial contrast uses an
area of multiple pixels in one frame as can be seen in the bottom left corner of
Figure 2. A window size of 5 x 5 or 7 x 7 pixels has been suggested for optimal
results. As spatial contrast decreases the spatial resolution, however, this method
does have a high temporal resolution. Temporal LSCI uses the same pixel in multiple
frames to calculate the contrast in a time window as can be seen in the top right
corner of Figure 2. Temporal contrast has a high spatial resolution and low temporal
resolution. For spatial contrast this is vice versa and hence, it can be beneficial
if combined into a so-called spatio-temporal contrast. The choice of resolution
should be based on the need for a high temporal or spatial resolution.
If the exposure time of the detector is shorter than the intensity fluctuation time
of the speckles, the standard deviation σ is equal to the mean intensity which
theoretically results in a contrast value of K=1. If there is movement present and
the exposure time of the detector is of the order of, or longer than the fluctuation
time, the picture will be blurred meaning that the standard deviation σ will be
small compared to the mean intensity which results in a loss of contrast, hence
0≥K<1.
1.5 Standard-of-care: Indocyanine green fluorescence imaging The use of ICG is
standard-of-care in the MCL and ICG and its application for perfusion assessment are
CE-certified and will be used as approved. The ICG procedure described in this
protocol is according to the standard MCL ICG protocol (See addendum K6.16).
Indocyanine green is a water-soluble anionic amphiphilic tricarbocyanine dye with a
molecular weight of 774.96 Da. It becomes completely and permanently fixed to plasma
proteins once in the bloodstream, and circulates in the intravascular compartment
only. This may allow for the blood flow of the gastric conduit to be visualized.
This dye can be injected into the human bloodstream with practically no adverse
effects. It becomes fluorescent upon excitation by a laser beam or by light with a
wavelength in the near infra-red (NIR) spectrum (approximately 820 nm). This dye was
first approved for clinical use in 1956 and is now, next to methylene blue the only
clinically food and drug administration (FDA) and European Medicines Agency (EMA)
approved fluorescent dye. Twenty-five mg of ICG will be dissolved in 10mL sterile
water (2.5mg/mL). The ICG fluorescence will be imaged using the Olympus Viscera
ELITE II infrared imaging system.
1.6 Rationale for the CONDOR-I study The current intraoperative assessment of
perfusion around the site for the anastomosis is based on subjective clinical
indicators of intestinal viability, i.e. the surgeon's eye and ICG-fluorescence
imaging. As indicated by others12 there is a need for a gold standard in determining
the state of microcirculation. This method should be suitable for laparoscopic use,
robust and preferably non-invasive. Our hypothesis is that PerfusiX-Imaging could be
this method. By comparing PerfusiX-Imaging to the current standard-of-care perfusion
assessment (i.e., ICG-fluorescence and the surgical eye), the most optimal method
for real-time feedback can be obtained and used for clinical decision-making during
surgery, which might be beneficial to the patient. This benefit can be the result of
two actions; (1) repositioning of the location of the anastomosis or (2) a change in
operating plan. Repositioning the location of the anastomosis is helpful when this
is repositioned in a better perfused area. A change in operating plan could be a
Roux-y reconstruction or a colon interponate instead of a gastric tube
reconstruction. In this prospective observational feasibility study, the
investigators aim to determine whether the added clinical value and whether the
operating plan would have changed, based on additional PerfusiX-imaging derived
visual feedback.
2. OBJECTIVES 2.1 Primary objectives Due to the explorative character of this study,
there is no formal hierarchy in the respective objectives of this study. In this,
all objectives will add to the overall assessment of the feasibility of the
PerfusiX-imaging derived visual feedback.
- To determine whether operating surgeons, based on additional PerfusiX-imaging
derived visual feedback, in hindsight would have changed the location of the
anastomosis or operating plan.
- To determine whether non-involved surgeons, based on additional
PerfusiX-imaging derived visual feedback, in hindsight would have changed the
location of the anastomosis or operating plan.
- To determine the change in location of the anastomosis (if indicated that the
anastomosis would be relocated) by the operating surgeon (in centimeters).
- To determine the change in location of the anastomosis (if indicated that the
anastomosis would be relocated) by non-involved surgeons (in centimeters).
- To determine the homogeneity of the decision to change the location between the
non-operating surgeons for individual patients.
- To determine if there is overlap between the location of the watershed area as
indicated by PerfusiX-Imaging, the ICG-fluorescence, and the surgical eye.
2.2 Secondary objectives Not applicable. 3. STUDY DESIGN The current study is a
prospective, observational single-center study in the Medical Center Leeuwarden. A total
of 30 patients undergoing an esophageal resection will be included (see section 4 'Study
population'). Patients will - after written informed consent - undergo the regular
standard-of-care program (i.e. perfusion assessment by means of the surgical eye and
ICG-fluorescence imaging). In addition to this standard-of-care, 2D-perfusion maps will
be generated from images taken with PerfusiX-Imaging (LIMIS Development BV, Leeuwarden,
The Netherlands) in combination with a standard, unmodified surgical laparoscope and
video system (EndoEye, Olympus Medical, Hamburg, Germany). The images will be shown to
the surgeon postoperatively and per operative questionnaires will be filled by the
surgeon. A detailed description of the safety aspects, application and specification of
these devices can be found in section 6 and 7. A detailed description of the imaging
protocol can be found in section 8.
4 STUDY POPULATION 4.1 Population All included patients meeting the eligibility criteria
and scheduled to undergo esophageal resection.
4.2 Inclusion criteria
In order to be eligible to participate in this study, the subject must meet all following
criteria:
- Scheduled to undergo esophageal resection;
- Age 18 years or older;
- Written informed consent; 4.3 Exclusion criteria
- Medical or psychiatric conditions that compromise the patient's ability to give
informed consent; 4.4 Sample size calculation For this explorative study, no formal
sample size calculation was performed. A total of 30 patients total is deemed
sufficient by experts to determine the effect of PerfusiX-Imaging on the surgeon's
clinical decision making. With this number of patients, it is likely for some
patients to develop anastomotic leakage. There is no consensus in the literature
regarding the incidence of AL in esophageal surgery. Numbers range between 8.5% and
24.5%.13-17 Assuming a 12.5% chance of anastomotic leakage, a total of 4 patients
out of 30 patients will develop anastomotic leakage. Data on patients developing AL
could be useful for future studies. For the assessments by the non-operating
surgeons, at least 5 non-involved surgeons will assess each patient case. Results of
this study will be used for a power size calculation for a possible subsequent
intervention study in order to determine the effectiveness of PerfusiX-Imaging as a
tool to prevent AL.
5 TREATMENT OF SUBJECTS 5.1 Investigational product/treatment The investigational
medical device is a medical imaging device that uses LSCI as a technology to image
perfusion of the gastric conduit. This technology is referred to in literature as
laser speckle contrast imaging, laser speckle contrast analyses or laser speckle
perfusion imaging. There is no change in treatment for the patients included in this
study. As ICG-fluorescence imaging and the surgical eye are used for the assessment
of the gastric conduit perfusion. The ICG-fluorescence device (Olympus, Hamburg,
Germany) is a CE-certified device that is used on label.
5.2 Use over co-intervention (if applicable) Not applicable. 5.3 Escape medication (if
applicable) Not applicable.
6 INVESTIGATIONAL DEVICE 6.1.2 Positioning in the operating room Positioning of the
research set-up is outside the sterile zone of the operating room (OR). The fiber optic
cable between the white light source and the laparoscope will be replaced by a connection
between the white light source and the investigational medical device.
6.2 Summary of findings from non-clinical studies Not applicable. 6.3 Summary of findings
from clinical studies A feasibility study has been published recently in the
international scientific journal "Biomedical Optics Express" which used a similar setup
as the current investigational device. In the first work, the feasibility of LSCI as a
tool for imaging perfusion is studied21. This work is proof that the investigational
medical device is capable of measuring perfusion. An experimental setup was developed
using a green 532nm and red 680nm laser and commercially available laparoscopic video
systems. Vascular occlusion tests (VOT) performed on the large intestines and the nail
fold were analyzed using custom software and were compared with published data. Ten
(n=10) subjects undergoing colonic resections were included in a two-center study and of
ten (n=10) healthy volunteers participated in the VOT nail fold experiment. The 532nm
laser showed significant differences of 90.46 ± 3.78% (p<0.0001) and 81.08 ± 4.22%
(p<0.0001) during occlusion, 107.51 ± 5.56% (p=0.005) and 108.53 ± 8.51% (p=0.148) during
reperfusion compared to the baseline for the intestines and nail fold respectively. Also,
the post-occlusion plateau differed significantly from baseline, 99.64 ± 6.11% (p=0.86),
on the nail fold. The 680nm laser showed a significant decrease, 81.08 ± 4.22%
(p<0.0001), during occlusion of the nail fold and did not show significant differences
during the other phases. This two-center study with ten (n=10) subjects undergoing a
colonic resection illustrates that laser speckle contrast imaging is capable of
identifying ischemic areas on the large intestine in a standard laparoscopic setup with a
measured flow decrease of up to 10% compared to baseline level. Other clinical
applications of LSCI can be found in this review 22.
Additionally, Milstein et al. have performed LSCI measurements one the gastric conduit
following esophagectomy with positive results. A notable difference between this study
and the study by Milstein et al. is that the investigators will use a laparoscopic LSCI
device as to compared to an open surgical device23.
6.4 Summary of know and potential risks and benefits See IMDD (Version 1.1, November
2020, section 5) for a summary of known and potential risks and benefits of laparoscopic
LSCI.
7 NON-INVESTIGATIONAL PRODUCT 7.1 Name and description of non-investigation product(s)
7.1.1 Olympus surgical OTV-S300 video processor The OTV-S300 is an all-in-one 2D/3D
processor and light source for laparoscopic surgeries. It is capable of both 2D and 3D
observation packed in a compact system for a simplified workflow. It has an LCD touch
panel that allows for presets for easy preparation and maintenance. It has an LED light
source which produces good natural color reproduction with the combination of enhanced
imaging processes. It has spectral light observation with narrowband imaging and two
modes of IR-observation.
8 METHODS 8.1 Study parameters/endpoints 8.1.1 Study parameter/endpoint Due to the
explorative character of this study, there is no formal hierarchy in the respective
endpoints of this study. In this, all endpoints will add to the overall assessment of the
feasibility of the PerfusiX-imaging derived visual feedback.
The investigators will look at the percentage of operating surgeons that indicated no
change in location of the anastomosis or operating plan based on the additional
PerfusiX-Imaging. The percentage of the non-involved surgeons that indicated no change in
location of the anastomosis or operating plan based on the additional PerfusiX-Imaging.
And the homogeneity of the change in location between non-involved surgeons for
individual patients will be analyzed in order to get a sense for the subjectivity of the
interpretation of the images.
The investigators will also compare the additional PerfusiX-Imaging derived visual
feedback to the standard of care by looking at the homogeneity in location of the
watershed area between PerfusiX-Imaging, ICG-fluorescence and based on visual assessment
by the surgical eye. The difference in the location of watershed area between
PerfusiX-Imaging and ICG-fluorescence or based on visual assessment.
In order to get a sense of the scale of the indicated change in location of the
anastomosis the investigators will look at the estimated change in location of the
anastomosis of the gastric conduit/ the esophageal stump in centimeters by the operating
surgeon. The estimated change in location of the anastomosis of the gastric conduit/ the
esophageal stump in centimeters by non-involved surgeons. Lastly, the investigators will
compare the change in the location of the anastomosis by non-involved surgeons in
comparison to the operating surgeon;
The overlap in location of the watershed area between the modalities (LSCI,
ICG-fluorescence and the surgical eye) will be determined to assess clinical
applicability of LSCI in esophagus-surgery.
8.1.2 Other study parameters/endpoints (if applicable)
- Not applicable 8.2 Randomization, blinding and treatment allocation The current
study is a non-randomized, non-blinded, prospective, single-center in which all
patients are scheduled to undergo a surgical procedure according to standard care.
There is no difference in therapeutic procedure among included patients.
8.3 Study procedures 8.3.1 Inclusion procedure Potential eligible patients are identified
by their treating physician (in Dutch: hoofdbehandelaar). The treating physician will
assess eligibility by checking in- and exclusion criteria based on the available data
(according to paragraph 4.2 and 4.3). If a patient is found to be eligible to participate
in the study, he or she will receive oral information about the study during a standard
clinic visit, several weeks prior to surgical procedure. In addition, he or she will
receive written study information (together with the standard information) and is asked
to consider participation. The patients will be informed about the aim of the study, the
procedures and associated risks before enrolment into the study. Also, patients will be
informed as to the strict confidentiality of their data.
Two weeks after receiving the information about the study, patients can inform their
treating physician or the secretary staff of the Chirurgie MCL in person, by phone, mail
or e-mail to confirm that they are willing to participate in this study. When patients
agree to participate, signed written informed consent is obtained. For more specified
information about informed consent, see chapter 11.2.
8.3.2 Image acquisition protocol The patient will be treated according to treatment plan
as was established by the treating physician. The surgical procedure is executed as is
deemed appropriate by the surgeon. The image acquisition protocol is executed in both the
thoracic and the abdominal phase of the surgery. There will be three imaging moments
where the investigators will image using PerfusiX-Imaging. Additionally, the
standard-of-care ICG-imaging and visual assessment will be noted based on the surgeons'
judgement. The three imaging moments are (1) baseline during the abdominal phase (2)
After making the gastric conduit and (3) imaging of the tip of the gastric conduit and
esophageal stump before making the anastomosis in the thoracic phase. This is represented
in the table below.
The LSCI images will NOT be shown during surgery to any surgeon. 8.3.3 Perioperative
visual assessment (operating surgeon) During the three measuring moments the on-site
investigator will ask the surgeon to fill out the short peroperative questionnaire based
on the visual inspection and ICG-fluorescence imaging of the state of perfusion of the
tissue.
8.3.4 Postoperative indication of change in clinical decision making (operating surgeon)
The investigators will show the images to the operating surgeon directly after surgery
and ask him/her whether he/she would change the location of the anastomosis or operating
plan based on the additional PerfusiX-Imaging derived visual feedback.
8.3.5 Postoperative change in clinical decision making (non-involved surgeon) After all
inclusions the investigator will ask other, non-involved surgeons to determine the
endpoints of this study concerning clinical decision making. The investigators will show
the images to the non-involved surgeons and ask them whether they would change the
location of the anastomosis based on the additional PerfusiX-Imaging derived visual
feedback. In this, each assessor (at least) 5 surgeons will first make his/her own
decision. Thereafter, consensus can be reached for inconclusive cases.
8.3.6 Anastomotic leakage check Minimally 30 days after the imaging procedure, the
investigators will examine the patients electronic patient file to check if the patient
was diagnosed by the treating surgeon with anastomotic leakage.
8.4 Withdrawal of individual subjects Subjects can leave the study at any time prior to
surgery for any reason if they wish to do so without any consequences. The investigator
can decide to withdraw a subject from the study for urgent medical reasons.
8.4.1 Specific criteria for withdrawal (if applicable) Subjects will be withdrawn from
the study when no surgery will be performed. 8.5 Replacement of individual subjects after
withdrawal Patient who are withdrawn will be replaced in this study. 8.6 Follow-up of
subjects withdrawn from treatment Not applicable. 8.7 Premature termination of the study
8.7.1 Termination based on safety aspects Not applicable 8.7.2 Termination based on other
aspects The study will be suspended based on urgent medical or ethical considerations as
decided by the principal investigators. In case of termination of the study, the
institution, regulatory authorities, CCMO and the METC of the study center will be
informed.
9 SAFETY MONITORING 9.1 Temporary halt for reasons of subject safety In accordance to
section 10, subsection 4 of the WMO, the sponsor will suspend the study if there is
sufficient ground that continuation of the study will jeopardize subject health or
safety. The sponsor will notify the accredited METC without undue delay of a temporary
halt including the reason for such an action. The study will be suspended pending a
further positive decision by the accredited METC. The investigator will take care that
all subjects are kept informed.
9.2 AEs, SAEs 9.2.1 Adverse events (AEs) Adverse events are defined as any undesirable
experience occurring to a subject during the study, whether or not considered related to
the investigational product. All adverse events reported spontaneously by the subject or
observed by the investigator or his staff will be recorded.
9.2.2 Serious adverse events (SAEs) A serious adverse event is any untoward medical
occurrence or effect that
- results in death;
- is life threatening (at the time of the event);
- requires hospitalization or prolongation of existing inpatients' hospitalization;
- results in persistent or significant disability or incapacity;
- is a congenital anomaly or birth defect; or
- any other important medical event that did not result in any of the outcomes listed
above due to medical or surgical intervention but could have been based upon
appropriate judgement by the investigator.
An elective hospital admission will not be considered as a serious adverse event.
The sponsor will report the SAEs through the web portal ToetsingOnline to the accredited
METC that approved the protocol, within seven days of first knowledge for SAEs that
result in death or are life threatening followed by a period of maximum of eight days to
complete the initial preliminary report. All other SAEs will be reported within a period
of maximum 15 days after the sponsor has first knowledge of the serious adverse events.
9.2.3 Suspected unexpected serious adverse reactions (SUSARs) Not applicable. 9.3 Annual
safety report Not applicable. 9.4 Follow-up of adverse events All AEs that are related to
the investigational medical product will be followed until they have abated, or until a
stable situation has been reached. Depending on the event, follow up may require
additional tests or medical procedures as indicated, and/or referral to the general
physician or a medical specialist. SAEs need to be reported till end of study within the
Netherlands, as defined in the protocol.
9.5 Data Safety Monitoring Board (DSMB) An independent external Data Safety Monitoring
Board of experts will not be instituted.
10 STATISTICAL ANALYSIS The overall aim of this study is to see if the use of additional
PerfusiX-Imaging derived visual feedback alters the determination the optimal location of
the anastomosis compared to the standard of care. For this the investigators determine
the percentage of surgeons that indicate no change in surgical plan based on the
additional PerfusiX-Imaging derived visual feedback. Descriptive statistics will include
measurements of distribution: (geometric) means with standard deviation; medians with
range; frequencies with 95% confidence interval.
11 ETHICAL CONSIDERATIONS 11.1 Regulation statement The study will be conducted according
to the principles of the Declaration of Helsinki (Fortaleza, Brazil, 2013 amendment) and
in accordance with the Medical Research Involving Human Subjects Act (WMO) and other
guidelines, regulations and Acts. The protocol has been written and the study will be
conducted according to the ICH Harmonized Tripartite Guideline for Good Clinical
Practice. The protocol will be approved by the Local, Regional or National Ethics
Committees.
11.2 Recruitment and consent Recruitment is done by the operating surgeon of the patient.
All subjects are informed and asked for their consent. The minimal time between first
appointment with doctor and surgery is 2 weeks, what results in a minimal time of 2 weeks
for consideration.
Written informed consent must be obtained for all patients included in the study before
they are registered in the study. Patients must be given adequate opportunity to read the
information and enquire about details of the study before consent is given. This implies
that the written informed consent form will be signed and personally dated by the
patient. The informed consent statement will be signed and dated by the investigator
afterwards and the patient will receive a copy. The general physician of each patient
will be informed about the enrollment of the patient to the study.
11.3 Objection by minors or incapacitated subjects (if applicable) Not applicable. 11.4
Benefits and risk assessment, group relatedness All patients included in the study will
be treated comparable with patients not included in the study. The difference between
non-included and included patients is prolonged operating time. Prolonged operating time
can increase the risk for patients, (e.g. infection (although this is rather minimal for
laparoscopic surgery) and prolonged narcosis. The results do not immediately benefit the
patients included in this study, but could help future patients to improve patient
outcome.
11.5 Compensation for injury
The sponsor/investigator has a liability insurance which is in accordance with article 7
of the WMO. The sponsor (also) has insurance which is in accordance with the legal
requirements in the Netherlands (Article 7 WMO). This insurance provides cover for damage
to research subjects through injury or death caused by the study. The total amounts of
insurance are as follows:
1. A maximum of €650.000 (i.e. six hundred and fifty thousand euros) for death or
injury for each subject who participates in this current research;
2. A maximum of €5.000.000 (i.e. five million five hundred thousand euros) for death or
injury for all subjects who participate in this current research;
3. A maximum of €7.500.000 (i.e. seven million five hundred thousand euros) for the
total damage that becomes apparent at the study participant in research which was
conducted by the Medical Center Leeuwarden. Act in each year of insurance coverage.
The insurance applies to the damage that becomes apparent during the study or within 4
years after the end of the study.
11.6 Incentives (if applicable) Not applicable.
12 ADMINISTRATIVE ASPECTS, MONITORING AND PUBLICATION 12.1 Handling and storage of data
and documents Data of patients will be handled confidentially and a coded identification
number (study protocol number 'CONDOR' followed by number of inclusion (for example
CONDOR01) will be used to link the data to the specific patient. Data that can be linked
to a specific patient will be stored separately. The principal investigator safeguards
the key to the code. The handling of the personal data complies with the EU General Data
Protection Regulation and the Dutch Act on Implementation of the General Data Protection
Regulation (in Dutch: Uitvoeringswet AVG, UAVG)). These data will be stored at the
specific site for at least fifteen years.
For software adjustments a software engineer from ZiuZ Research BV can have access to
only the images. All images are coded with the patient number, location of image, type of
image, with/without surgical clip and only accessible by a password. For example:
"60-D-LSCI-SCY" This describes an image of patient 60, distal end, LSCI image, surgical
clip is placed.
12.3 Amendments
Amendments are changes made to the research after a favorable opinion by the accredited
METC has been given. All amendments will be notified to the METC that gave a favorable
opinion. A 'substantial amendment' is defined as an amendment to the terms of the METC
application, or to the protocol or any other supporting documentation, that is likely to
affect to a significant degree:
- the safety or physical or mental integrity of the subjects of the trial;
- the scientific value of the trial;
- the conduct or management of the trial; or
- the quality or safety of any intervention used in the trial. All substantial
amendments will be notified to the METC and to the competent authority.
Non-substantial amendments will not be notified to the accredited METC and the
competent authority, but will be recorded and filed by the sponsor.
12.4 Annual progress report The sponsor/investigator will submit a summary of the
progress of the trial to the accredited METC once a year. Information will be provided on
the date of inclusion of the first subject, numbers of subjects included and numbers of
subjects that have completed the trial, serious adverse events/ serious adverse
reactions, other problems, and amendments.
Criteria for eligibility:
Study pop:
All patients meeting the eligibility criteria and scheduled to undergo esophageal
resection in the Medical Center Leeuwarden.
Sampling method:
Probability Sample
Criteria:
Inclusion Criteria:
- Scheduled to undergo esophageal resection;
- Age 18 years or older;
- Written informed consent;
Exclusion Criteria:
- Medical or psychiatric conditions that compromise the patient's ability to give
informed consent;
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Medical Center Leeuwarden
Address:
City:
Leeuwarden
Zip:
8934 AD
Country:
Netherlands
Status:
Recruiting
Start date:
September 26, 2022
Completion date:
May 31, 2024
Lead sponsor:
Agency:
Medical Centre Leeuwarden
Agency class:
Other
Collaborator:
Agency:
University of Groningen
Agency class:
Other
Collaborator:
Agency:
LIMIS Development
Agency class:
Other
Source:
Medical Centre Leeuwarden
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05685862
