Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05897060 |
| Other study ID # |
2022-A02770-43 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
May 11, 2023 |
| Est. completion date |
October 30, 2023 |
Study information
| Verified date |
May 2023 |
| Source |
Braindex |
| Contact |
Thierry CUSSAC |
| Phone |
+33(7)82230369 |
| Email |
thierry.cussac[@]braindex.fr |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The objective of this clinical trial is to optimize Braindex brain tissue oxygen saturation
(SctO2) measurement algorithm compared to a mixed reference value of jugular venous and
systemic arterial saturation, during proven reproducible and standardized loss of brain
autoregulation induced during transcatheter aortic valve replacement procedures. The main
question it aims to answer is: assessing and improving the sensitivity/specificity of
Braindex SctO2 measurements.
Study type: single-center, prospective, interventional, open-label, exploratory clinical
trial.
Participant population/health status:
- Patient, male or female, over 18 years of age
- Patient scheduled for percutaneous femoral aortic valve replacement with aortic valve
balloon deployment (Edwards Sapien valve) under simple sedation with Remifentanil
(TIVA), with spontaneous ventilation.
The expected outcome of this research is to optimize in vivo the algorithm for calculating
the SctO2 of the BRAINDEX sensor in surgical conditions, in a context of proven low cerebral
flow, on a target population. It is expected, in the long run, a better quality of detection
of the loss of cerebral auto-regulation leading to a faster and optimal correction, thus
potentially limiting the risk of POCD, subcortical stroke and postoperative cognitive
decline.
Description:
SPONSOR BRAINDEX sas Parc Eurasanté 12 avenue Pierre Mauroy 59120 Loos
INVESTIGATOR COORDINATOR Professor Julien AMOUR Institut de Perfusion, de Réanimation et
d'Anesthésie de Chirurgie Cardiaque Paris Sud (IPRA) Hôpital Privé Jacques Cartier 6 avenue
du Noyer Lambert 91300 Massy, France
TITLE In vivo optimization study of the algorithm for measuring cerebral tissue oxygen
saturation (SctO2) by Braindex compared with a mixed reference value of jugular venous and
systemic arterial saturation during proven loss of cerebral auto-regulation.
ID-RCB NUMBER 2022-A02770-43
JUSTIFICATION / BACKGROUND The incidence of postoperative cognitive impairment (POCD) in
cardiac surgery is of the order of 30-50%. Loss of cerebral autoregulation is a factor in
POCD and cognitive decline. Cerebral near-infrared oximetry (NIRS), a commercially available
non-invasive monitoring system, aims to detect and limit the loss of cerebral autoregulation
during intraoperative hemodynamic instability.
NIRS currently measures cerebral tissue oxygen saturation (SctO2) over a patchy tissue
volume, and corresponds to blood sampling comprising arterial, venous and capillary
components.
The performance of cerebral oximetry devices currently on the market has been clinically
validated to a limited extent, often in healthy volunteers with no comorbidity, or in
cardio-vascular situations (hypoxemia tests) outside any surgical procedure. For a number of
devices, test results have been extrapolated and marketed without any real per-procedural
clinical validation, and without being able to fully assert the correlation between a real
loss of cerebral autoregulation, which is difficult to affirm, and the fall in SctO2. Beyond
clinical validation, the various devices present a number of limitations and technical
imperfections, notably a restricted sampling zone, a low number of transmitters and
receivers, and variable signal processing algorithm quality. All these factors may explain
the mixed results of recent clinical meta-analyses concerning the benefits of this
technology.
The BRAINDEX sensor offers the advantage of an optical imager equipped with 60 LEDs emitting
6 wavelengths (660, 730, 780, 810, 850 and 900nm) and 28 photodiodes (optical sensors). This
set of optodes translates into a measurement of 420 optical vectors per cerebral hemisphere,
enhancing the resolution of cerebral oxygenation measurement and the number of analysis zones
compared with current devices on the market.
Initial efficiency tests have already been carried out in silico using simulation models and
on a test bench. We now wish to optimize and calibrate the signal analysis algorithm for
measuring cerebral tissue oxygen saturation (SctO2) in vivo, in a context of proven loss of
cerebral autoregulation, and compare it with a mixed value of jugular venous and systemic
arterial saturation, a commonly accepted reference.
In this sense, percutaneous aortic valve replacement or TAVI (Sapiens valve, Edwards) offers
the decisive advantage of generating a standardized and perfectly reproducible circulatory
arrest, leading to a planned loss of cerebral autoregulation, throughout the duration of
aortic valve occlusion by the valve deployment balloon.
The aim of the research is to optimize the Braindex algorithm in vivo during the TAVI
procedure, and in particular during the loss of cerebral autoregulation linked to circulatory
arrest systematically induced by valve deployment. This study will also rely on the
measurement of jugular venous oxygen saturation (SvjO2) and arterial oxygen saturation
(SaO2), which are the reference measurements for the previous devices.
OBJECTIVES The primary objective of this research is to optimize an algorithm for estimating
SctO2 (SctO2Exp.), in vivo, in patients scheduled for a femoral TAVI procedure and
systematically exposed to a period of loss of cerebral autoregulation during deployment of
the percutaneous aortic valve.
Secondary objectives are:
- To evaluate the quality of EEG (electroencephalogram) signals from electrodes in the
BRAINDEX sensor,
- Evaluate the possibility of calculating the ANI (Analgesia Nociception Index) from PPG
(photoplethysmography) signals obtained with the BRAINDEX sensor
- Study the technical performance of the BRAINDEX sensor.
RESEARCH SCHEME This is an exploratory, prospective, interventional, open clinical
investigation aimed at developing and optimizing the algorithm for estimating SctO2Exp.
INCLUSION CRITERIA
- Patient, male or female, over 18 years of age
- Patient undergoing percutaneous aortic valve replacement with aortic valve balloon
deployment (Edwards Sapien valve) under simple sedation with remifentanil in AIVOC, with
spontaneous ventilation
- Patient affiliated to or entitled under a social security scheme
- Patient having received written and informed information about the study and having
signed a free and informed consent to participate in the study.
NON-INCLUSION CRITERIA
- Emergency surgery
- Patient weighing less than 40kg
- Patient with history of ischemic stroke
- Patient with a contraindication to catheterization arterial catheters
- Patient with a contraindication to the Braindex device
- Protected patient: adult under guardianship, curatorship or other legal protection
deprived of liberty by judicial or administrative decision
- Pregnant, parturient or breast-feeding women
- Patient hospitalized without consent
RESEARCH PROCEDURE The research procedure consists in optimizing the Braindex algorithm for
measuring in vivo SctO2Exp before, during and after a proven loss of cerebral autoregulation
linked to circulatory arrest programmed by percutaneous aortic valve deployment via
transvalvular balloon, on a vigorous patient sedated with remifentanil in IVCA.
Continuous measurement of SvjO2, the usual reference measurement for commercially available
devices, will be performed by implanting an optical fiber
(CEVOX,PULSIONMedicalSystemsSEHans-Riedl-Str.17 85622 Feldkirchen Germany) through an
internal jugular catheter, in addition to the conventional external electro systolic drive
catheter. The following parameters will be recorded every 2 seconds: invasive blood pressure
(systolic, mean and diastolic), heart rate, SaO2 on the pulse wave. SvjO2 will be recorded
continuously throughout the implantation procedure. The times at which the surgical incision
begins, the onset of sinus tachycardia (overdriving) induced by external electro-systolic
stimulation, the start of inflation of the intra-avalvular aortic balloon, maximum balloon
occlusion, the end of complete balloon deflation, the end of stimulation and the end of skin
closure will be recorded.
Jugular venous and arterial gasometry (1 ml per sample) will be taken to perform initial
calibration of the CEVOX fiber at the start of the procedure (skin incision), then before
overdriving, then when overdriving is stopped and finally at the end of skin closure, to
ensure that there is no derivation of the estimated continuous value of the CEVOX fiber.
ADDED ACT Placement of the CEVOX probe for continuous SvjO2 monitoring will be performed
under local anaesthetic, in addition to remifentanil sedation, under ultrasound guidance.
Installation of the BRAINDEX non-invasive forehead sensor.
EVALUATION CRITERIA
Primary endpoints :
- NIRS (Near-infrared spectroscopy) signals recorded via the BRAINDEX sensor to optimize
the algorithm
- SctO2Exp value obtained from jugular measurement to optimize algorithm.
Secondary endpoints :
- EEG signals recorded via BRAINDEX sensor and three-axis acceleration information via
accelerometer
- PPG (photoplethysmocardiography) signals via BRAINDEX sensor and ANI signals via ANIv2
monitor
- Sensor operation, optode detachment, electrode detachment
STUDY SIZE As this is an exploratory study, no statistical hypothesis could be defined. As
the main objective of the study is to optimize an in vivo algorithm for estimating SctO2Exp,
it is important to obtain a sample representative of the diversity of hemodynamic situations
observed during TAVI procedures, which offer the advantage of being highly standardized and
reproducible. The inclusion of 40 patients should enable us to achieve this diversity. The
inclusion of 40 patients should enable us to achieve this diversity.
INTENDED NUMBER OF CENTERS One center: Institut de Perfusion, de Réanimation et d'Anesthésie
de Chirurgie Cardiaque Paris Sud (IPRA) at Hôpital Privé Jacques Cartier (Massy).
DURATION OF RESEARCH
- Length of inclusion period: 10 months (projected start date of IC: 01/03/2023)
- Duration of each participant's participation: duration of the surgical procedure with
follow-up of adverse events during the 24 postoperative hours.
- Total research duration: 10 months and 24 hours (projected end of CI: 05/01/2024).
STATISTICAL ANALYSIS OF DATA Analyses will be performed on all included patients. Main
analysis NIRS signals collected over the entire operative period of the TAVI procedure will
be used to develop the algorithm for calculating SctO2Exp.
The raw data will be denoised using a butter Worth 0.05Hz order 6 low-pass filter and
subtracting potential artifacts, external light interference and high-frequency interference
(physiological and caused by the electromagnetic environment). The regional oxygen
concentration SctO2Exp will then be calculated using the modified Beer-Lambert law, expressed
by the equation below, on all optical vectors, In order to optimize the algorithm obtained,
the concentrations thus estimated, SctO2Exp, will be compared with the reference measurement,
SctO2Ref (estimated as being equal to 25% SaO2 and 75% SvjO2), and will be used to group
together the distances and vectors required for a more accurate estimate of oxygen
saturation.
Secondary analysis
Evaluation of EEG signal quality:
- EEG signal quality in the face of physiological and environmental artefacts environmental
artifacts associated with the TAVI procedure (patient handling, electromagnetic environment,
etc.), will be assessed by calculating a signal-to-noise ratio defined by the power density
in the spectral band of interest (0.1 - 4hz) divided by the remaining spectral content and
signal saturation indicators (considered saturated if greater than ±200mV). The proportion of
saturated ratio will be described, - Signal variations in relation to voluntary or
involuntary movements of the patient's head measured along 3 axes will be calculated. A
variation of more than 0.5g in any axis will be considered as a head movement (voluntary or
involuntary). The proportion of variation over 0.5g will be described.
Assessment of the possibility of calculating ANI :
- The PPG signals recorded by the BRAINDEX sensor will be used to calculate ANI. The
agreement between the ANI obtained from the PPG signals via the BRAINDEX sensor and the ANI
obtained from the ANIv2 monitor will be assessed using the intraclass correlation coefficient
(ICC) and the graphical method of Bland and Altman. The ICC and its 95% confidence interval
will be determined using a 2-factor random analysis of variance, patient and method.
Study the technical performance of the BRAINDEX sensor:
- The operational reliability of the BRAINDEX sensor will be assessed using a log file
indicating potential abnormal operation of the system
- The identification of optode detachment during measurement will be evaluated by
estimating the variance of ambient noise with diodes off
- The indication of electrode detachment during measurement will be evaluated by
estimating the impedance of the electrodes by the acquisition component
EXPECTED BENEFITS The expected spin-offs of this research are to optimize the BRAINDEX
sensor's SctO2Exp calculation algorithm in vivo, under actual patient management conditions,
in proven situations of loss of cerebral auto regulation.
