E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Tissue adhesion/sealing and suture support in neurosurgery and surgical procedures where contact with cerebrospinal fluid or dura mater can occur e.g. otologic, rhinologic, ophthalmic and vertebral surgery. |
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E.1.1.1 | Medical condition in easily understood language |
This study is designed to test the use of Evicel in sealing the dura mater,
a layer which covers the brain, during neurosurgery. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
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 objective of this study is to evaluate the safety and efficacy of Evicel for use as an adjunct to dura sutures in elective cranial surgery to provide watertight closure. |
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E.2.2 | Secondary objectives of the trial |
- Incidence of CSF leakage within approximately 5 days (+/-2) postoperatively.
- Incidence of CSF leakage within approximately 30 days (+/-3) post operatively.
- Incidence of adverse events
- Dural sealing related adverse events (i.e. CSF leaks, pseudomeningocele formation, etc.)
- Incidence of surgical site infections (SSI) according to National Nosocomial Infection Surveillance (NNIS) criteria approximately 30 days (+/- 3) post-operatively. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Preoperative
• Patient undergoing elective craniotomy/craniectomy for pathological processes in the posterior fossa (such as benign and malignant tumors, vascular malformation, and Chiari 1 malformations) or in the supratentorial region and who are demonstrated to have persistent CSF leakage following suture closure of the dural incision. CSF leakage will be evaluated during a period of Valsalva of 20-25 cm of H20 for 5-10 seconds.
• Administration of perioperative antibiotic prophylaxis
• Age >= 18 years
• Patients who are able and willing to comply with the procedures required by the protocol.
• Signed and dated written informed consent from the subject or from his/her legal representative prior to any study-related procedures.
Intraoperative
• Surgical wound classification Class I. Penetration of mastoid air cells during partial mastoidectomy is permitted.
• The cuff of native dura along the craniotomy edge is wide enough based on the surgeon's judgement to facilitate suturing and to allow for sufficient surface area for adherence of the investigational product. |
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E.4 | Principal exclusion criteria |
Preoperative:
• Subjects with a dura lesion from a recent surgery that still has the potential for CSF leakage.
• Chemotherapy scheduled within 7 days following surgery.
• Radiation therapy to the head scheduled within 7 days following surgery.
• Long-term (6 months) low dose steroid therapy for existing chronic/inflammatory conditions to be resumed within 7 days following surgery. However, postoperative tapered high-dose steroids are permitted.
• Subjects with severely altered renal function as confirmed by local lab reference ranges for serum creatinine and/or hepatic function [ALT, AST > 5 x upper limit of norm (ULN)]
• Evidence of an infection indicated by any one of the following: clinical
diagnosis of infection, fever, positive urine culture, positive blood culture, positive chest X-ray, evidence of infection along the planned surgical path. A WBC count of <20000 is permitted if the patient is being treated with steroids in the absence of all the other infection parameters.
• Conditions or treatments significantly compromising the immune system (such as AIDS).
• Known hypersensitivity to the components (human fibrinogen, arginine hydrochloride, glycine, sodium chloride, sodium citrate, calcium chloride, human thrombin, human albumin, mannitol and sodium acetate) of the investigational product.
• Non-compliant or insufficient treatment of diabetes mellitus in the opinion of the investigator.
• Hydrocephalus, except occlusive hydrocephalus caused by posterior fossa pathology to be treated.
• Existing CSF (ventricular, etc.) drains. Cushing/Dandy cannulation or Burr holes which damage the dura.
• Female subjects of childbearing potential with a positive urine or serum pregnancy test within 24 hours prior to surgery.
• Female subjects who are breastfeeding, pregnant, or intend to become pregnant during the clinical study period.
• Participation in another clinical trial with exposure to another investigational drug or device within 30 days prior to enrollment.
• Scheduled or foreseeable surgery within the follow-up period.
Intraoperative:
• Dura injury during craniotomy/craniectomy that cannot be eliminated by widening the craniotomy/craniectomy to recreate the native dura cuff.
• Use of implants made of synthetic materials coming into direct contact with dura (e.g., PTFE patches, shunts, ventricular and subdural drains).
• Planned use of dural patches after primary suture closure of the dura.
• Placement of Gliadel Wafers
• Chiari 1 subjects without injury to the arachnoid.
• Persistent signs of increased brain turgor
• Patient has a gap of greater than 2mm after primary dural closure.
• Intersecting durotomy scars in the surgical path from a previous operation that cannot be completely removed by the planned dura resection.
• Two or more separate dura defects
• Major intraoperative complications that require resuscitation or deviation from the planned surgical procedure. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of success (watertight closure) in the treatment of intra-operative CSF leakage defined as no CSF leakage from dural repair intra-operatively, during Valsalva maneuver up to 20-25 cm H2O for 5 to 10 seconds |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.8.1.3 | Single blind | Yes |
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 |
additional dural sutures as deemed necessary by the surgeon |
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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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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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Last visit of the last subject |
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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 | 5 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |