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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E.1.1.1 | Medical condition in easily understood language |
Patients undergoing skull based surgery |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Surgical Procedures, Operative [E04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067908 |
E.1.2 | Term | Neurosurgery |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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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 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 postoperatively. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to evaluate the safety of TachoSil as an adjunct in sealing the dura mater. |
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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 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 considered 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 undergo non-trauma related neurosurgery for pathology of the skull base resulting in opening and closing of the dura mater? Dura substitution is allowed. 5. Has a CT or MRI scan of the head been performed within 4 month before screening?
Intra-operative Inclusion Criteria – positive response required for inclusion: 6. Is the Surgical Wound Classification Class of class I (Clean surgical wound)? (Clean wound definition: Uninfected surgical wounds in which no inflammation is encountered and the respiratory, alimentary, genital, or uninfected urinary tracts are not entered. In addition, clean wounds are primarily closed, and if necessary, drained with closed drainage) 7. 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 retrosigmoid 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. |
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E.4 | Principal exclusion criteria |
Pre-operative Exclusion Criteria – negative response required for inclusion: 1. Has the patient been randomised in another clinical trial with an investigational medicinal product or device within 28 days before screening for this trial? (Participation in non-interventional studies is allowed) 2. Has the patient previously participated in this trial? 3. Does the patient have evidence of an infection within 5 days of surgery 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 > 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. Has the patient been subject to neurosurgery involving opening of the dura matter within the last 3 months before Screening for this trial? 7. Is the patient anticipated to undergo any additional neurosurgery involving opening of the dura matter which may affect the efficacy evaluation (e.g. re-operation or anticipation to undergo several neurosurgeries) before the Efficacy Follow-up 7±1 week? 8. Is the patient anticipated to undergo any additional neurosurgery involving opening of the dura matter 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?
For females of childbearing potential, i.e. neither postmenopausal (less than 12 months after the last menstruation) nor permanently sterilised (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy): 9. 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, vasectomised partner or double barrier contraception? 10. Has the contraceptive method been used too short to be effective? 11. Has the female patient had a positive serum pregnancy test taken within 5 days prior to surgery? All females not documented as postmenopausal or permanently sterile must have a serum pregnancy test performed. 12. Breastfeeding?
Intra-operative Exclusion Criteria – negative response required for inclusion: 13. The surgical approach/procedure is consistent with any transcranial or transfacial or combination of transcranial – transfacial approaches with wide defect in the skull base? any of the following: a. Trans basal approach, b. Total petrosectomy, c. Trans facial approach, d. Trans sphenoidal approach, e. Endoscopic procedures, f. Trans oral approach (and any extension: Le Fort, mandibulotomy). 14. The surgical approach is consistent with one of the following approaches? a. Translabyrinthine approach b. Retrolabyrinthine approach c. Transcochlear (limited transpetrosal) approach 15. Did the arachnoid membrane and the CS containing system remain intact during surgery? 16. Does the patient have more than one dura opening (not including dura openings from extraventricular or lumbar drains)? 17. Has TachoSil, fibrin or polymer sealants been used during the current surgery prior to randomisation? |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint must be considered as reached if a clinically evident CSF- leak or a clinically evident pseudomeningocele has occurred post-operatively and until Efficacy Follow-up (week 7±1) or if treatment failure has occurred. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoint must be considered as reached if a clinically evident CSF- leak or a clinically evident pseudomeningocele has occurred post-operatively and until Efficacy Follow-up (week 7±1) or if treatment failure has occurred. |
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E.5.2 | Secondary end point(s) |
The secondary endpoint must be considered as reached if a non-clinically evident pseudomeningocele has occurred post-operatively and until Day of Discharge without achieving the primary endpoint. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The secondary endpoint must be considered as reached if a non-clinically evident pseudomeningocele has occurred post-operatively and until Day of Discharge without achieving the primary endpoint. |
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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.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
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 | No |
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 |
Austria |
Belgium |
France |
Germany |
Greece |
Italy |
Netherlands |
Poland |
Russian Federation |
Spain |
Sweden |
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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 | 10 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |