E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Skull base surgery for the prevention of postoperative cerebrospinal fluid (CSF) leaks |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067908 |
E.1.2 | Term | Neurosurgery |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to assess the efficacy of TachoSil as an adjunct in sealing the dura mater in order to prevent postoperative CSF-leakage / clinically evident pseudomeningocele following skull base surgery. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to assess the safety of TachoSil as an adjunct in sealing the dura mater to prevent postoperative CSF-leakage / clinically evident pseudomeningocele following skull base surgery. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Pre-operative Inclusion Criteria – positive response required for inclusion: 1. Has written informed consent been obtained according to local regulations before any trial-related activities? (A trial-related activity is any procedure that would not have been performed during the routine management of the patient.) 2. Is the patient able and willing to comply with the procedures required for trial completion? 3. Is the patient 18 years or above? 4. Is the patient to non-trauma related neurosurgery for pathology of the skull base resulting in opening and closing of the dura mater? Dura substitution is allowed.
Intra-operative Inclusion Criteria – positive response required for inclusion: 5. Is the Surgical Wound Classification Class of class I (Clean surgical wound)? 6. Is the surgical approach/procedure consistent with skull base surgery? I.e. at least one of the following: a. Lateral approach to the foramen magnum: far lateral, extreme lateral, anterolateral, posterolateral, b. Approach to the jugular foramen: infratemporal, juxta condylar, transjugular, c. Approach to the cerebello pontine (CP) angle and petrous apex retrosigmoïd, translabyrinthine, retrolabyrinthine, transcochlear (limited transpetrosal), d. Approach to the middle fossa: subtemporal (+/- petrous apex drilling), pterional approach (any fronto temporal approach +/- orbitozygomatic deposition), e. Approach to the anterior fossa: subfrontal (uni or bilateral), f. Approach to the midline posterior fossa or paramedian posterior fossa.
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E.4 | Principal exclusion criteria |
Pre-operative Exclusion Criteria – negative response required for inclusion: 1. Has the patient participated in another clinical trial with an investigational drug or device within 28 days of inclusion in this trial? (Participation in non-interventional trials is allowed) 2. Has the patient previously participated in this trial? 3. Does the patient have evidence of an infection indicated by any one of the following: fever >101°F / 38.5°C, white blood cells (WBC) <3.5/GL or >13.0/GL (if patient on steroid treatment up to 20.00/GL), positive urine culture, positive blood culture, positive chest Xray? 4. Does the patient have a known coagulopathy? 5. Does the patient have a history of allergic reactions after application of human fibrinogen, human thrombin and / or collagen of any origin? 6. Is the patient anticipated to need additional neurosurgery within the follow-up period of Week 7±1 at the same surgical site?
For females of childbearing potential, i.e. neither postmenopausal (less than 12 month after the last menstruation) nor permanently sterilised (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy): 7. Does the female patient use an unacceptable contraceptive method or method ineffective at the time of randomisation, i.e. do not use a contraceptive method which is a highly effective method of birth control; defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices or vasectomised partner? 8. Has the female patient had a positive serum pregnancy test taken up to 5 days prior to surgery? All females not documented as postmenopausal or permanently sterile must have a serum pregnancy test performed. 9. Breastfeeding?
Intra-operative Exclusion Criteria – negative response required for inclusion: 10. 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: g. Trans basal approach, h. Total petrosectomy, i. Trans facial approach, j. Trans sphenoïdal approach, k. Endoscopic procedures, l. Trans oral approach (and any extension: Le Fort, mandibulotomy). 11. Did the arachnoid membrane remained intact during surgery and/or the liquor containing system? |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the occurrence of either a clinically evident CSF-leak or a clinically evident pseudomeningocele |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Standard treatment for closure of the dura or duraplasty |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end-of-trial is defined as last patient last visit. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |