Cerebrospinal Fluid Leak
Conditions
Keywords
Fibrin sealant, CSF leak
Brief summary
The objective of this study is to evaluate the safety and efficacy of EVICEL® Fibrin Sealant (Human) for use as an adjunct to sutured dural repair in cranial surgery.
Interventions
BIOLOGICALEVICEL Fibrin Sealant
DEVICEHydrogel sealant
Sponsors
Ethicon, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects ≥18 years of age undergoing craniotomy/craniectomy for pathological processes in the supratentorial region or posterior fossa * Subjects or legally authorized representatives must be willing to participate in the study and provide written informed consent. * Surgical wound classification Class I * The cuff of native dura along the craniotomy edge on each side is adequate, based on surgeon's judgment, to facilitate suturing and to allow for sufficient surface area for adherence of the investigational product * Presence of intra-operative cerebrospinal fluid (CSF) leakage following primary dural closure or after Valsalva maneuver
Exclusion criteria
* Subjects with a dural lesion from a recent surgery that still has the potential for CSF leakage. * Chemotherapy within 30-days prior to enrollment or scheduled within 7-days following surgery * Radiation therapy to the head within 30-days prior to enrollment or scheduled within 7-days following surgery * A previous craniotomy/craniectomy within 6 months prior to the study surgery. * Known hypersensitivity to the components of the investigational product. * Subjects with a known allergy to FD&C Blue #1 dye * Subjects with an infection present at the surgical site * Subjects with an infection indicated by any one of the following: clinical diagnosis of infection, fever, positive urine culture, positive blood culture, positive chest X-ray. * Female subjects of childbearing potential with a positive pregnancy test or intent to become pregnant during the clinical study period. * Female subjects who are nursing. * Exposure to another investigational drug or device clinical trial within 30 days prior to enrollment or anticipated in the 60 day follow-up period. * Subjects with severely altered renal or hepatic function, with a compromised immune system or autoimmune disease who can NOT receive hydrogel sealant. * Subjects with penetratring traumatic injuries to the head with damage to the dura * Dural injury during craniotomy/craniectomy that cannot be eliminated by widening the craniotomy/craniectomy to recreate the native dural cuff. * Patient has a gap between durotomy edges of greater than 2mm after primary dural closure. * Approaches that would not allow sutured dural closure such as trans-sphenoidal or trans-labirinthine-/petrosal/-mastoid. Superficial penetration of mastoid air cells are allowed. * Use of implants made of synthetic materials coming into direct contact with dura * Use of other fibrin sealants or PEG-based sealants on the dural closure. Approved fibrin sealants may be used for hemostasis if not in contact with the dura. * Hydrocephalus, except occlusive hydrocephalus caused by posterior fossa pathology or incompletely open cerebrospinal fluid pathways, to be treated during surgical procedure. * Placement of Gliadel Wafers * Intersecting durotomy scars in the surgical path from a previous operation that cannot be completely removed by the planned dural resection. * Two or more separate cranial dural defects, including defects from ventricular cannulation and ventriculo-peritoneal shunting. * Subjects with any other intra-operative findings identified by the surgeon that may preclude the conduct of the study procedure. * Confined bony structures where nerves are present where neural compression may result due to swelling.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Effectiveness Endpoint Success Number of Successes (Subjects That Had no Inter-operative CSF Leak Following Valsalva Maneuver and no CSF Leak or Pseudomeningocele in the Surgical Area During the 30-day Follow-up Period) | Intraoperatively through 30-day follow-up | The primary endpoint was the proportion of subjects that had no inter-operative CSF leak following Valsalva maneuver and no CSF leak or pseudomeningocele in the surgical area during the 30-day follow-up period |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety Endpoint: Intra-operative CSF Leakage Follow Final Valsalva | Intraoperatively, after final Valsalva maneuver | Intra-operative CSF leakage follow final Valsalva |
Countries
Australia, Belgium, Canada, New Zealand, United Kingdom, United States
Participant flow
Recruitment details
Subjects were recruited from medical centers in North America, Europe, and Asia-Pacific. The first subject was randomized on July 7 2015 and the last subject completed the study October 12 2017
Participants by arm
| Arm | Count |
|---|---|
| Evicel EVICEL® is a human plasma-derived fibrin sealant. EVICEL® consists of two components: a concentrate of Human Fibrinogen (referred to as Biological Component 2; BAC2) and a solution of Human Thrombin, which incorporates calcium. | 114 |
| DuraSeal DuraSeal™ Dural Sealant System is a commercially available synthetic sealant intended for use as an adjunct to sutured dural repair during cranial surgery to provide watertight closure. The product is a synthetic absorbable sealant composed of a polyethylene glycol (PEG) ester solution and a rilysine amine solution. | 120 |
| Total | 234 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lost to Follow-up | 4 | 1 |
| Overall Study | Other reasons | 4 | 1 |
| Overall Study | Refused to complete study/procedures | 1 | 1 |
Baseline characteristics
| Characteristic | DuraSeal | Evicel | Total |
|---|---|---|---|
| Age, Continuous | 56.0 years STANDARD_DEVIATION 15 | 53.4 years STANDARD_DEVIATION 14.9 | 54.7 years STANDARD_DEVIATION 15 |
| BMI | 26.9 kg/m^2 STANDARD_DEVIATION 5 | 27.5 kg/m^2 STANDARD_DEVIATION 6 | 27.2 kg/m^2 STANDARD_DEVIATION 5.5 |
| BMI (Grouped) Morbidly Obese | 0 Participants | 4 Participants | 4 Participants |
| BMI (Grouped) Normal | 46 Participants | 37 Participants | 83 Participants |
| BMI (Grouped) Obese | 34 Participants | 27 Participants | 61 Participants |
| BMI (Grouped) Overweight | 39 Participants | 45 Participants | 84 Participants |
| BMI (Grouped) Underweight | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity Hispanic | 3 Participants | 2 Participants | 5 Participants |
| Ethnicity Non-Hispanic | 117 Participants | 112 Participants | 229 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 9 Participants | 9 Participants | 18 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 3 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Other | 4 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized White/Caucasian | 101 Participants | 102 Participants | 203 Participants |
| Sex: Female, Male Female | 59 Participants | 59 Participants | 118 Participants |
| Sex: Female, Male Male | 61 Participants | 55 Participants | 116 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 114 | 2 / 120 |
| other Total, other adverse events | 103 / 114 | 109 / 120 |
| serious Total, serious adverse events | 32 / 114 | 37 / 120 |
Outcome results
Primary
Primary Effectiveness Endpoint Success Number of Successes (Subjects That Had no Inter-operative CSF Leak Following Valsalva Maneuver and no CSF Leak or Pseudomeningocele in the Surgical Area During the 30-day Follow-up Period)
The primary endpoint was the proportion of subjects that had no inter-operative CSF leak following Valsalva maneuver and no CSF leak or pseudomeningocele in the surgical area during the 30-day follow-up period
Time frame: Intraoperatively through 30-day follow-up
Population: Per Protocol Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Evicel | Primary Effectiveness Endpoint Success Number of Successes (Subjects That Had no Inter-operative CSF Leak Following Valsalva Maneuver and no CSF Leak or Pseudomeningocele in the Surgical Area During the 30-day Follow-up Period) | Posterior Fossa | 22 Participants |
| Evicel | Primary Effectiveness Endpoint Success Number of Successes (Subjects That Had no Inter-operative CSF Leak Following Valsalva Maneuver and no CSF Leak or Pseudomeningocele in the Surgical Area During the 30-day Follow-up Period) | Supratentorial | 73 Participants |
| Evicel | Primary Effectiveness Endpoint Success Number of Successes (Subjects That Had no Inter-operative CSF Leak Following Valsalva Maneuver and no CSF Leak or Pseudomeningocele in the Surgical Area During the 30-day Follow-up Period) | Total | 95 Participants |
| DuraSeal | Primary Effectiveness Endpoint Success Number of Successes (Subjects That Had no Inter-operative CSF Leak Following Valsalva Maneuver and no CSF Leak or Pseudomeningocele in the Surgical Area During the 30-day Follow-up Period) | Posterior Fossa | 23 Participants |
| DuraSeal | Primary Effectiveness Endpoint Success Number of Successes (Subjects That Had no Inter-operative CSF Leak Following Valsalva Maneuver and no CSF Leak or Pseudomeningocele in the Surgical Area During the 30-day Follow-up Period) | Supratentorial | 69 Participants |
| DuraSeal | Primary Effectiveness Endpoint Success Number of Successes (Subjects That Had no Inter-operative CSF Leak Following Valsalva Maneuver and no CSF Leak or Pseudomeningocele in the Surgical Area During the 30-day Follow-up Period) | Total | 92 Participants |
95% CI: [-1.8, 14.4]
Other Pre-specified
Safety Endpoint: Intra-operative CSF Leakage Follow Final Valsalva
Intra-operative CSF leakage follow final Valsalva
Time frame: Intraoperatively, after final Valsalva maneuver
Population: No Valsalva maneuver performed in 2 participants in the Evicel Arm and 1 participant in the DuraSeal Arm
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Evicel | Safety Endpoint: Intra-operative CSF Leakage Follow Final Valsalva | 10 Participants |
| DuraSeal | Safety Endpoint: Intra-operative CSF Leakage Follow Final Valsalva | 13 Participants |