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. |
|
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. |
|
E.2.2 | Secondary objectives of the trial |
- Incidence of CSF leakage as detected by clinical observation or as observed on T2 Gradient Echo MRI by Day 5 post-operatively. - Incidence of CSF leakage as detected by clinical observation or as observed on T2 Gradient Echo MRI 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.
|
|
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 cm of H20 for 5-10 seconds. • Age 3 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 10 mm wide, to facilitate suturing and to allow for sufficient surface area for adherence of the investigational product.
|
|
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 low dose steroid therapy to be resumed within 7 days following surgery. However, postoperative tapered high-dose steroids are permitted. • Subjects with severely altered renal (serum creatinine > 2 mg/dL) and/or hepatic function ALT, AST > 5 x upper limit of norm (ULN) • Evidence of an infection indicated by any one of the following: fever > 38C, WBC < 3500/uL or > 13000/uL, 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 compromising the immune system; existence of autoimmune disease. • 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 glycosylated hemoglobin (HbA1c) > 7.5%. • Hydrocephalus, except occlusive hydrocephalus caused by posterior fossa pathology to be treated. • Existing CSF (ventricular, etc.) drains. Burr holes are permitted as long as the dura remains intact. Cushing cannulation excludes the subject. • 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. • Failure to administer preoperative antibiotic prophylaxis • Use of implants made of synthetic materials coming into direct contact with dura (e.g., PTFE patches, shunts, ventricular and subdural drains). • 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.
|
|
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 cm H2O for 5 to 10 seconds |
|
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 |
|
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 | 11 |
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 |
|
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
|
last visit of the last subject |
|
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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |