TASALL - TachoSil® Against Liquor Leak

Study Overview
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Brief Summary
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The primary objective is to demonstrate superiority of TachoSil® compared to current practice as an adjunct in sealing the dura mater. The efficacy of the dura mater sealing must be evaluated post-operatively. The secondary objective is to evaluate the safety of TachoSil® as an adjunct in sealing the dura mater. The trial population will consist of 726 randomised (1:1) patients elected for skull base surgery. The trial duration consists of screening, surgery, efficacy follow-up after 7±1 weeks and safety follow-up 28±2 weeks after surgery.

Official Title
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TachoSil® Versus Current Practice in Dura Sealing Techniques for the Prevention of Post-operative Cerebrospinal Fluid (CSF) Leaks in Patients Undergoing Skull Base Surgery: An Open Label, Randomised, Controlled, Multi-centre, Parallel Group Efficacy and Safety Trial.

Conditions
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Cerebrospinal Fluid Leaks

Intervention / Treatment
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* Procedure: TachoSil®
* Procedure: Current Practice


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria (Positive response): • Is the surgical approach/procedure consistent with skull base surgery? I.e. one of the following: Lateral approach to the foramen magnum: Far lateral, extreme lateral, anterolateral, posterolateral Approach to the jugular foramen: Infratemporal, juxta condylar, transjugular Approach to the cerebello pontine (CP) angle and petrous apex retrosigmoid Approach to the middle fossa: Subtemporal (+/- petrous apex drilling), pterional approach (any fronto temporal approach +/- orbitozygomatic deposition) Approach to the anterior fossa: Subfrontal (uni or bilateral) Approach to the midline posterior fossa Main Exclusion Criteria (Negative response): Has the patient been subject to neurosurgery involving opening of the dura mater within the last 3 months? Is the patient anticipated to undergo any additional neurosurgery involving opening of the dura mater which may affect the efficacy evaluation (e.g. re-operation or anticipation to undergo several neurosurgeries) before the Efficacy Follow-up Week 7±1 week? Is the patient anticipated to undergo any additional neurosurgery involving opening of the dura mater which may affect the safety evaluation (e.g. re-operation or anticipation to undergo several neurosurgeries) before the Safety Follow-up Week 28±2 weeks? The surgical approach/procedure is consistent with any transcranial or transfacial or combination of transcranial - transfacial approaches with wide defect in the skull base? I.e. any of the following: Trans basal approach Total petrosectomy Trans facial approach Trans sphenoidal approach Endoscopic procedures Trans oral approach (and any extension: Le Fort, mandibulotomy) The surgical approach is consistent with one of the following approaches? Translabyrinthine approach Retrolabyrinthine approach Transcochlear (limited transpetrosal) approach Did the arachnoid membrane and the CSF containing system remain intact during surgery? Does the patient have more than one dura opening (not including dura openings from extraventricular or lumbar drains)? Has TachoSil, fibrin or polymer sealants been used during the current surgery prior to randomization?

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TachoSil®<br> | Procedure: TachoSil®<br>* Primary suture must be performed. Duraplasty may be performed at the discretion of the investigator. TachoSil® must be applied under aseptic conditions during the closure of the dura.<br>|
| Active Comparator: Current practice group<br> | Procedure: Current Practice<br>* Primary suture must be performed. Duraplasty may be performed at the discretion of the investigator. In addition to primary suture, whatever means of dura closure deemed necessary by the investigator may be used with the exception of TachoSil®.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Clinically Evident Verified Post-Operative Cerebrospinal Fluid Leak or Clinically Evident Pseudomeningocele or Treatment Failure | An assessment was performed daily from randomization to Day of Discharge and at the Efficacy Follow-up visit at week 7 ± 1 week. Clinically evident cerebrospinal fluid leak was confirmed by: 1. Glucose concentration test and/or 2. β-2-transferrin test. A clinically evident pseudomeningocele was considered to be present post-operatively if the following criteria were fulfilled: 1. A subcutaneous, visible/palpable fluctuant fluid accumulation was noted at the site of the surgical incision or adjacent to it; 2. It is suspected the fluid accumulation is cerebrospinal fluid. A treatment failure was defined as application of a new and/or different treatment after application of the study treatment or a third application of (or part of) the selected study treatment on the outside of the dura. | Up to 8 Weeks (7 Weeks ± 1 Week) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Post-Surgical Non-Clinically Evident Post-Operative Pseudomeningocele | Non-clinically evident pseudomeningocele was defined as a cerebrospinal fluid accumulation found on a postoperative computerized tomography (CT) or magnetic resonance imaging (MRI) scan which fulfilled the following criteria according to the radiologist assessment before Day of Discharge: CT Scan-Fluid accumulation seen as Hypodense signal, MRI Scan-Fluid accumulation seen as Hypointense signal in T1-weighted image and/ OR Fluid accumulation seen as Hyperintense signal in T2-weighted image. | Assessment at least once prior to discharge from neurosurgical ward, with the expected discharge from neurosurgical ward after an average of 10 days (Up to 28 Weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CSF leaks, Skull base surgery, pseudomeningocele, TachoSil®, Prevention, post-operative