TASALL - TachoSil® Against Liquor Leak

• ClinicalTrials.gov Identifier: NCT01355627
• Recruitment Status: Completed
• First Posted: May 18, 2011
• Results First Posted: July 25, 2014
• Last Update Posted: July 25, 2014
• Sponsor: Takeda
• Information provided by (Responsible Party): Takeda

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Cerebrospinal Fluid Leaks	Procedure: TachoSil®; Procedure: Current Practice	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 726 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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.
• Study Start Date: April 2011
• Actual Primary Completion Date: June 2013
• Actual Study Completion Date: June 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: TachoSil®	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.
Active Comparator: Current practice group	Procedure: 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®.

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Clinically Evident Verified Post-Operative Cerebrospinal Fluid Leak or Clinically Evident Pseudomeningocele or Treatment Failure [ Time Frame: Up to 8 Weeks (7 Weeks ± 1 Week) ]
   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.

Secondary Outcome Measures :

1. Percentage of Participants With Post-Surgical Non-Clinically Evident Post-Operative Pseudomeningocele [ Time Frame: 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) ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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?

Contacts and Locations

Locations

Austria

Nycomed Investigational Site

Graz, Austria, 8036

Belgium

Nycomed Investigational Site

Brussels, Belgium, 1070

Nycomed Investigational Site

Genk, Belgium, 3600

Nycomed Investigational Site

Leuven, Belgium, 3000

Nycomed Investigational Site

Liege, Belgium, 4000

France

Nycomed Investigational Site

Grenoble, France, 38043

Nycomed Investigational Site

Le Kremlin Bicetre, France, 94270

Nycomed Investigational Site

Marseille, France, 13005

Nycomed Investigational Site

Nice, France, 6002

Nycomed Investigational Site

Paris, France, 75010

Nycomed Investigational Site

Strassbourg, France, 67000

Nycomed Investigational Site

Toulouse, France, 31059

Germany

Nycomed Investigational Site

Freiburg, Germany, 79106

Nycomed Investigational Site

Halle, Germany, 6112

Nycomed Investigational Site

Homburg, Germany, 66421

Nycomed Investigational Site

München, Germany, 81925

Nycomed Investigational Site

Rostock, Germany, 18057

Greece

Nycomed Investigational Site

Athens, Greece, 10676

Nycomed Investigational Site

Athens, Greece, 15123

Nycomed Investigational Site

Thessaloniki, Greece, 54636

Italy

Nycomed Investigational Site

Genova, Italy, 16128

Nycomed Investigational Site

Lecce, Italy, 73100

Nycomed Investigational Site

Palermo, Italy, 90127

Nycomed Investigational Site

Siena, Italy, 53100

Netherlands

Nycomed Investigational Site

Dammers, Netherlands, 3015 CE

Poland

Nycomed Investigational Site

Gdansk, Poland, 80-803

Nycomed Investigational Site

Gdansk, Poland, 80-952

Nycomed Investigational Site

Warszawa, Poland, 02-781

Russian Federation

Nycomed Investigational Site

Moscow, Russian Federation, 125047

Spain

Nycomed Investigational Site

Barcelona, Spain, 8035

Nycomed Investigational Site

Barcelona, Spain, 8036

Nycomed Investigational Site

El Palmar, Spain, 30120

Nycomed Investigational Site

Madrid, Spain, 28049

Nycomed Investigational Site

Majadahonda, Spain, 28222

Nycomed Investigational Site

Malaga, Spain, 29010

Nycomed Investigational Site

Santiago de Compostela, Spain, 15706

Sweden

Nycomed Investigational Site

Göteborg, Sweden, 41345

Nycomed Investigational Site

Lund, Sweden, 22185

Nycomed Investigational Site

Stockholm, Sweden, 17176

Sponsors and Collaborators

Takeda

Investigators

• Study Chair: Nycomed; Clinical Trial Operations

More Information

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT01355627
• Other Study ID Numbers: TC-2402-038-SP
• First Posted: May 18, 2011
• Results First Posted: July 25, 2014
• Last Update Posted: July 25, 2014
• Last Verified: June 2014

Keywords provided by Takeda:

CSF leaks; Skull base surgery; pseudomeningocele; TachoSil®; Prevention; post-operative

Additional relevant MeSH terms:

Cerebrospinal Fluid Leak; Neurologic Manifestations; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries