Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT02048553 |
| Other study ID # |
05092013 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
September 4, 2013 |
| Last updated |
January 27, 2014 |
| Start date |
March 2014 |
| Est. completion date |
December 2016 |
Study information
| Verified date |
January 2014 |
| Source |
University Hospital, Geneva |
| Contact |
Asita S Sarrafzadeh, MD |
| Phone |
0041 22 37 28206 |
| Email |
asita.sarrafzadeh[@]hcuge.ch |
| Is FDA regulated |
No |
| Health authority |
Switzerland: Ethikkommission |
| Study type |
Interventional
|
Clinical Trial Summary
Background: Despite the widespread use of external ventricular drainage, revision rates and
associated complications are reported between 10-40%. Current available image-guided
techniques using stereotaxis, endoscopy or ultrasound for catheter placements remain
time-consuming techniques. Recently, a phone-assisted guide with high precision has been
described. The development of an easy-to-use, portable, image-guided system could reduce the
need for multiple passes and improve the rate of accurate catheter placement. This study aim
to compare prospectively in a randomized controlled manner the accuracy of the freehand pass
technique versus an an easy-to-use, portable mini-tablet-assisted guide for ventriculostomy
catheter placement.
Methods/Design: This is a single center, prospective, randomized, trial with blinded
endpoint (ventricle catheter tip location) assessment. Adult patients with the indication
for ventriculostomy, as proven by computed tomography (CT), will be randomly assigned to the
treatment group or the control group. In patients of the treatment group, ventriculostomy
will be performed using a mini-tablet-guided assistance based on preoperative CT imaging.
Patients in the control group will receive standard free-hand ventriculostomy using
anatomical landmarks. The catheter may be placed for external drainage or internal
(ventriculoperitoneal) shunting in both groups. The primary outcome measure is rate of
correct placements of the ventricular catheter, defined as a score of 1 to 3 on grading
system for catheter tip location on postoperative CT scan. Primary outcome will be
determined by one of the authors (NS) blinded for treatment allocation. We aim to include
320 patients in 3 years.
Secondary Outcome Measures include 1) Frequency of placements required, 2) Frequency of
completed placements within the ventricle of the perforated part of the tip of the catheter,
3) Frequency of very early and early shunt failures (revision of the ventricular drainage
within 24 hours / within three weeks, 4) Frequency and Percentage of complications
(procedure-related and nonsurgical) within three weeks, 5) Length of the trajectories from
the dura level to the foramen of Monroe, the angle in the coronal plane towards midline (a)
and towards the target (b) at the respective entry point, 6) ventricle size (the frontal
occipital horn ratio (FOHR) and the width of the lateral ventricle in the coronal plane
between the medial wall of the corpus callosum and the septum), 7) Differences (angles,
distance of catheter tip from target) on the tablet-guided planned and postoperative
trajectory on control computer tomography within 48 hrs (CT).
Discussion: Here, we present the study design of a single center prospective randomized
controlled trial to investigate whether tablet-guided application ventriculostomy is
superior to the standard free hand technique. The strengths of this study are: 1. the
prospective, randomized interventional character testing a new easy-to handle guided versus
free-hand ventricular catheter placement, and 2. the power calculation is based on catheter
accuracy using an available grading system for catheter tip location and calculated with use
of recent study results of our own population, supported by data from prominent studies.
Description:
Methods Design The Tablet-guided versus freehand ventriculostomy (TABGUIDE) study will be
performed as a 2-arm randomized controlled single-center trial to compare an intervention
group using a guided placement of a ventricular catheter to a control group receiving
standard (free-hand) ventriculostomy with blinded endpoint (catheter tip location)
assessment.
Setting The present study is in compliance with the Helsinki Declaration. The protocol of
this study was approved by the Ethics Committee on Human Research (CER) of the Medical
Faculty of the University of Geneva, Switzerland (reference number: CER 13-175). At the
planned start of the study at 01. March 2014, the study center will start randomization.
Randomization The randomization will start as soon as possible after consent to the study
has been obtained. Any patient meeting the inclusion criteria and not violating the
exclusion criteria may participate in the TABGUIDE study and be randomized to either a
guided or freehand ventriculostomy, thus defining the two distinct groups " guided " or "
freehand ". Online randomization will be performed by the treating physician in the study
center using permuted blocks, to ensure an equal number of patients in both study arms.
Interventions - Surgical technique
The study is conducted in the neurosurgical department of a swiss single center university
hospital in adult patients with indication for a ventricular drainage (such as
hydrocephalus, slit ventricles, pseudotumor cerebri). Data management and monitoring will be
performed by the Geneva study center and statistical analysis by one of the authors (NS).
For guidance, an easy-to handle instrument assisted by a mini-I-pad (mini-tablet)application
software (Apple Inc.) is used in order to achieve precise placement of ventricular catheters
on an every-case basis. The catheter may be placed for external drainage or internal
(ventriculoperitoneal, VP) shunting.
For patients in the guided group, catheter placement is performed in the operating theatre
during anesthesia under routine sterile conditions and antibiotic prophylaxis. The
phone-assisted technique used for guided placing of a ventricular catheter through an burr
hole has been previously described in detail. The only difference is the use of a
easy-to-use portable mini-tablet available for all neurosurgeons instead of a phone. In
brief, the patient is positioned and draped in typical sterile fashion for ventriculostomy
(if necessary enlarged for shunt placement). Using a standard adult perforator (14 mm;
AESCULAP, Germany), a frontal burr hole is made.
The guiding instrument consists of a base with three pins in order to be rigidly placed on
the bone surface over the burr hole. A semicircular guide rod is mounted to the base in
which an angle scale is engraved. Within the guide rod, a tube can be individually adjusted
in one orientation at different angulations with a range from -600 to 600. Different tubes
are designed with inner diameters of 2, 2.5, and 3 mm in order to guide catheters at
different sizes. At the respective angle adjustment, the tube is fixed to the guide rod by a
mounting screw. The base is opened at one side to enable the view or insert any instrument
towards the lower opening of the tube. The guiding tool is positioned parallel to the
midline along the engraved linear markings on the base of the instrument. Thereby, a
rectangular insertion towards the sagittal convexity and an individual insertion angle
towards the coronal tangent at the entry point can be established via the tube.
After dura opening, once the appropriate trajectory is chosen, the catheter is inserted
according to the precalculated insertion angle. After tactile feedback of entering the
ventricle, the stylet is removed. Cerebrospinal fluid (CSF) drainage ensures that the
ventricular catheter is sufficiently in place. Catheters deemed to be suboptimally placed
are repositioned when necessary. We rely on length markings on the ventricular catheter and,
when possible, flow through the distal catheter to ensure the catheter has not been moved
after fixation on the skin and is continuing to provide a conduit for CSF. The remainder of
the possibly following shunt procedure or connection to a Ommaya reservoir was performed
with standard techniques.
The classical freehand technique uses anatomical landmarks and the catheter is placed in the
anterior horn of the lateral ventricle through a burr hole just anterior to the coronal
suture in the pupillary line (at the level of Kocher`s point, a point on the surface of the
cranium 2.5 cm from the midline and 1 cm anterior to the coronal suture). The target is the
ipsilateral frontal horn just anterior to the foramen of Monroe to avoid the chorioid
plexus. The right nondominant side is preferred. The catheter is directed freehand using
external landmarks in the coronar plane towards the ipsilateral medial canthus and in the
sagittal plane through the external auditory meatus. A post-procedural CT scan of the brain
is performed within 24 hours as part of standard care for postoperative control or earlier
in case of postoperative CSF drainage problems.
Mini-Tablet application Regular digital imaging (DICOM) viewing software, commonly used in
clinics, to evaluate radiological imaging, integrates simple measurement tools (e.g.
distance or angle measurements). This technique is used to define a trajectory with an entry
point at the frontal paramedian convexity towards the foramen of Monroe in a coronal
section. Then, measurements can be taken to determine the angle between the trajectory and
the respective tangent at the entry point on the skull surface. An I-Phone (Apple Inc., USA)
software application available is used, importing anonymous imaging material. This image
should be a coronal section with the lateral ventricles shown at the level of the anterior
commissure. The next step is to define a paramedian entry point on the surface of the skull
by tapping the finger on the respective spot. Then, the two feet are virtually placed on the
skull surface. A rectangular trajectory orientation of the tube is then shown as a dotted
line and can be shifted if necessary. The angle deviation from a rectangular insertion is
then given by the software as a value. In addition, the finger may be placed on the target
within the ventricle, and the length of the catheter will be given as distance value. As
alternative, the CT scan (at the level : coronal section with the lateral ventricles shown
at the level of the anterior commissure) can be photographed and used for angle
calculations.
Consent procedure Patients capable of consenting will be informed about the study details
themselves and may or may not agree to participate. If the patient or his/her legal
representative refuses consent after inclusion by advice of an independent physician, the
patient's further study participation is no longer possible. In this case, however, the
patient or his/her legal representative is asked to give consent for evaluation of already
acquired data. The detailed explanation of the study to the patient, legal representative
has to be carried out using appropriate explanations and words depending on the previous
medical knowledge of the respective person and her/his level of education. During the
explanations, the respective person will be asked on a regular basis if she/he understands
the conveyed information and if any questions have arisen. In addition to these verbal
explanations the patient/legal representative will be given a leaflet containing the study
details. After reading the leaflet the respective person will be given as much time as
she/he demands for the decision on study participation.
This study evaluates the outcome of an intervention performed often in an emergency
situation. Since approximately half of patients will not be able to give informed consent at
admission, the informed consent procedure for this study will be delayed in a so-called
emergency procedure. If neither the patient is capable of giving informed consent nor a
family representative (informed consent) is available in due time, an independent
neurosurgeon not involved in the patient's treatment nor in the trial may be asked for study
approval. This option was introduced into the consent procedure because data on smart-phone
guided ventriculostomy suggest a potentially beneficial effect of the measure for the
patient - however performed in a small group of 35 patients. Therefore it shall not be
categorically withheld from patients who are not capable of deciding whether to participate
in the study or not and who do not have a legal representative. As soon as a legal
representative / family representative is available and/or the patient is capable again to
consent to the study, he or she must be asked to give informed consent.
Sample Size Analysis Sample size analysis estimates (hit and miss rates) were based on the
results of observational studies. In a recent single center study of our group on the
accuracy of ventricular catheter placement, using anatomic landmarks versus neuronavigation
or CT-laser guidance, ventricles were hit in 69.2% of catheter insertions (31% miss rate)
using anatomical landmarks (non-assisted), as compared to 82.3% with the use of guidance
(neuronavigation or CT-guidance, p=0.043) (submitted data). The placements that were
non-assisted were significantly more likely to be placed extraventricularly than those using
guidance (OR 3.73, 95%, Confidence Interval (CI) 1.24, 11.19, p=0.019). Given data from
other retrospective studies on ventricular catheters (in the context of
ventricular-peritoneal shunts), similar rates between 25-45%4-7 of malpositioning are
described.
To detect a decrease in the incidence of malpositioning from 35% to 20, 151 patients in each
of the two study arms are needed to gain a power of 80%, using an alpha error of 5%. The
final planned study size is to include and randomize 302 patients.
Data Management Data specified in the trial protocol will be documented in the patient`s
digital records. Additional clinical data are available from the electronic patient files.
The investigating physician is responsible for appropriate completion of the form. The
authors (AS, NS) are responsible for data base development, data acquisition, data storage,
and validation. Data validation includes controls of completeness, consistence and
plausibility of the data documented in electronic dossier using a query system between data
management and investigating physician.
Adverse events (AE) and severe adverse events (SAE) The term " adverse event " (AE)
describes any sign, symptom, syndrome or any disease 1. Occurring newly in a trial
participant after consent to the trial and 2. Being of particular interest for the
assessment of the disease or the security of the therapeutic concept. Any AE is documented
in the electronic file of the patient.
Definition of Adverse Events (AE):
1. - Impairment of the general condition of the patient,
2. - Physical injury, including falls,
3. - Infection other than wound infection, sepsis or SIRS,
4. - Intracranial bleeding in the proximity of the ventricular catheter,
5. - Wound infection or dehiscence at the emersion site of the ventricular catheter,
7 - Newly occurred neurological deficit, 8 - Arterial or venous thrombosis, 9 - Any
suspicious findings that may have relationship to the study.
Definition of Serious Adverse Events (SAE):
10 - Fatal events / Death, 11 - Any Life-threatening condition, 12 - Disabling or
incapacitating events, 13- Events that require prolongation of hospitalization, 14 -
Required intervention to prevent permanent impairment.
Relation (as cause or result) to other AE/SAE:
0 - No, 1 - Possible (give brief description), 2 - Yes (give brief description).
Investigator's estimation of the severity of the problem to the study or study device (fill
in only, if AE/SAE is or might be related to study) 1 - Mild, 2 - Severe, 3 - Life
Threatening.
Investigator's recommendation to change the protocol, informed consent or assent form 0 -
No, 1 - Yes (give brief description).
Outcome of AE or SAE (until discharge)
1 - Full recovery, 2 - Permanent deficit, 3 - Not yet fully recovered, 4 - Not known.
Reporting & Statistical Analysis The reporting of this trial will conform to the reporting
guidelines outlined in the CONSORT statement of 2010. The statistical analysis will be by
intention-to-treat. The occurrence of the primary outcome, number and frequency of correct
ventriculostomy, will be compared between the two randomization groups. The secondary
outcome analyses will compare the above described variables between randomization groups.
Subgroup analyses will be performed to evaluate whether other parameters such as age,
ventricle size, diagnosis or experience of the surgeon may influence the results. Data are
presented as mean and standard deviation or as median with 25/75 percentiles. Stata version
11.2 (College Station, Texas) will be used for all analyses.
Interim analyses This trial will follow a group sequential design, with 2 stop-points
(interim and final analysis). The trial will stop if efficacy rules are met. The endpoints
assessed at the first stop-point will be based on primary outcomes and adverse events. The
first will be the interim analysis will occur after the accrual of 50 patients in each arm
(100 total) thus representing approximately 1/3 of trial accrual. For the efficacy
stop-point, a p-value of 0.001 at interim and 0.05 at final analysis will be used.
