TASALL - TachoSil® Against Liquor Leak

Cerebrospinal Fluid Leaks Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01355627
• Other study ID #: TC-2402-038-SP
• Status: Completed
• Phase: Phase 3
• First received: May 11, 2011
• Last updated: June 26, 2014
• Start date: April 2011
• Est. completion date: June 2013

Study information

• Verified date: June 2014
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: EthikkommissionBelgium: Federal Agency for Medicinal Products and Health ProductsFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Paul-Ehrlich-InstitutGreece: National Organization of MedicinesItaly: The Italian Medicines AgencyNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsRussia: Ethics CommitteeSpain: Agencia Española de Medicamentos y Productos SanitariosSweden: Regional Ethical Review Board
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 726
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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?

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cerebrospinal Fluid Leaks

Intervention

Procedure:
• TachoSil®
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.
• Current Practice
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®.

Locations

Country	Name	City	State
Austria	Nycomed Investigational Site	Graz
Belgium	Nycomed Investigational Site	Brussels
Belgium	Nycomed Investigational Site	Genk
Belgium	Nycomed Investigational Site	Leuven
Belgium	Nycomed Investigational Site	Liege
France	Nycomed Investigational Site	Grenoble
France	Nycomed Investigational Site	Le Kremlin Bicetre
France	Nycomed Investigational Site	Marseille
France	Nycomed Investigational Site	Nice
France	Nycomed Investigational Site	Paris
France	Nycomed Investigational Site	Strassbourg
France	Nycomed Investigational Site	Toulouse
Germany	Nycomed Investigational Site	Freiburg
Germany	Nycomed Investigational Site	Halle
Germany	Nycomed Investigational Site	Homburg
Germany	Nycomed Investigational Site	München
Germany	Nycomed Investigational Site	Rostock
Greece	Nycomed Investigational Site	Athens
Greece	Nycomed Investigational Site	Athens
Greece	Nycomed Investigational Site	Thessaloniki
Italy	Nycomed Investigational Site	Genova
Italy	Nycomed Investigational Site	Lecce
Italy	Nycomed Investigational Site	Palermo
Italy	Nycomed Investigational Site	Siena
Netherlands	Nycomed Investigational Site	Dammers
Poland	Nycomed Investigational Site	Gdansk
Poland	Nycomed Investigational Site	Gdansk
Poland	Nycomed Investigational Site	Warszawa
Russian Federation	Nycomed Investigational Site	Moscow
Spain	Nycomed Investigational Site	Barcelona
Spain	Nycomed Investigational Site	Barcelona
Spain	Nycomed Investigational Site	El Palmar
Spain	Nycomed Investigational Site	Madrid
Spain	Nycomed Investigational Site	Majadahonda
Spain	Nycomed Investigational Site	Malaga
Spain	Nycomed Investigational Site	Santiago de Compostela
Sweden	Nycomed Investigational Site	Göteborg
Sweden	Nycomed Investigational Site	Lund
Sweden	Nycomed Investigational Site	Stockholm

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Countries where clinical trial is conducted

Austria,  Belgium,  France,  Germany,  Greece,  Italy,  Netherlands,  Poland,  Russian Federation,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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. ß-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)	No
Secondary	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)	No