Dura Defects, Pathological Processes in the Posterior Fossa
Conditions
Brief summary
The purpose of this study is to investigate the efficacy and safety of FS VH S/D 500 s-apr, a double virus-inactivated biological two-component fibrin sealant, for use in posterior fossa surgery as an adjunct to dura and dura substitute sutures in preventing postoperative cerebrospinal fluid (CSF) leakage.
Interventions
Application of a thin layer of FS VH S/D 500 s-apr to the entire length of the suture loop and the adjacent area to at least 5 mm away from the suture line, including all suture holes. After application, the product is to be allowed to polymerize for 3 minutes.
PROCEDUREStandard of care
Standard care: defined as the closure of a dura defect by suturing in a patch of autologous fascia, pericranium or suturable collagen-based dura substitute.
Sponsors
Baxter Healthcare Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
3 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Preoperative Inclusion Criteria: * Subjects undergoing elective craniotomy / craniectomy for pathological processes in the posterior fossa (such as benign and malignant tumors, vascular malformations, and Chiari 1 malformations) that result in dura defects requiring dura substitution for closure and 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 * Age \>= 3 years, either gender Intraoperative Inclusion Criteria: * Surgical Wound Classification Class I and Risk Index Category (RIC) \<= 2. Penetration of mastoid air cells during partial mastoidectomy is permitted and will be recorded. * A patch of autologous fascia or pericranium or suturable collagen-based dura substitute was cut to size and then sutured into the dura defect. * The hem of native dura exposed along and under the craniotomy edge is wide enough to facilitate suturing and to allow for sufficient surface area for adherence of the investigational product.
Exclusion criteria
Preoperative
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Cerebrospinal Fluid (CSF) Leakage Observed After Surgery | 33 +/- 3 days after surgery | Study-relevant CSF leakage is defined as one or more of following: 1. Discrete subcutaneous or subgaleal CSF collection (pseudomeningocele) in surgical area confirmed by positive test for β2-transferrin, or by computed tomography (CT) or magnetic resonance imaging (MRI) 2. Epidural CSF collection in surgical area depicted by CT or MRI 3. Leakage of CSF through surgical wound observed during physical examination, confirmed by a positive test for β2-transferrin 4. Progressive pneumatocephalus (air in subarachnoidal space) depicted by repeat CT in absence of CSF drainage. |
| Number of Participants With Cerebrospinal Fluid (CSF) Leakage Observed After Surgery | 33 +/- 3 days after surgery | Study-relevant CSF leakage is defined as one or more of following: 1. Discrete subcutaneous or subgaleal CSF collection (pseudomeningocele) in surgical area confirmed by positive test for β2-transferrin, or by computed tomography (CT) or magnetic resonance imaging (MRI) 2. Epidural CSF collection in surgical area depicted by CT or MRI 3. Leakage of CSF through surgical wound observed during physical examination, confirmed by a positive test for β2-transferrin 4. Progressive pneumatocephalus (air in subarachnoidal space) depicted by repeat CT in absence of CSF drainage. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Surgical Site Infections (SSI) According to National Nosocomial Infection Surveillance (NNIS) Criteria | within 1 month following surgery | — |
| Number of Participants With Surgical Site Infections (SSI) According to National Nosocomial Infection Surveillance (NNIS) Criteria | within 1 month following surgery | — |
| Number of Participants With Procedures Resulting From the Treatment of CSF Leaks | until resolution or 30 days after final follow-up visit (Day 33+/-3), whichever is first | The number of participants with surgical revisions, number and duration of compression bandage applications and of liquor drainage procedures. |
| Incidence of Procedures Resulting From the Treatment of CSF Leaks | until resolution or 30 days after final follow-up visit (Day 33+/-3), whichever is first | The incidence of surgical revisions, number and duration of compression bandage applications and of liquor drainage procedures |
Countries
Canada, United States
Participant flow
Recruitment details
Participants were enrolled at 12 United States and 1 Canadian clinical site(s) beginning May 2008 and completing in March 2010
Pre-assignment details
95 were enrolled. 23 discontinued (10 screen failures, 3 withdrawn by investigator, 3 withdrawn by representative or self, 1 died- failure to thrive, 1 had surgery before randomized, 1 study site distance, 1 site reached enrollment goal, 2 patients cancelled surgery, 1 family delayed \>30 day window. 62 randomized. There were 13 run-in participants.
Participants by arm
| Arm | Count |
|---|---|
| Standard of Care (SoC) The closure of a dura defect by suturing in a patch of autologous fascia, pericranium or suturable collagen-based dura substitute. | 28 |
| FS VH S/D 500 S-apr (Run-In Participants Only) Application of thin layer of FS VH S/D 500 s-apr to entire length of suture loop and adjacent area to at least 5 mm away from the suture line, including all suture holes. After application, the product is to be allowed to polymerize for 3 minutes. Note: This arm/group only includes the 13 initial run-in participants (one for each site permitted to familiarize the investigators with the study procedures) | 13 |
| FS VH S/D 500 S-apr (Non Run-In Participants Only) Application of thin layer of FS VH S/D 500 s-apr to entire length of suture loop and adjacent area to at least 5 mm away from the suture line, including all suture holes. After application, the product is to be allowed to polymerize for 3 minutes. Note: This arm/group does not include the 13 initial run-in participants (one for each site permitted to familiarize the investigators with the study procedures) | 34 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 0 | 1 | 0 |
| Overall Study | scheduling conflict | 1 | 0 | 0 |
| Overall Study | withdrawn by investigator | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Standard of Care (SoC) | FS VH S/D 500 S-apr (Run-In Participants Only) | FS VH S/D 500 S-apr (Non Run-In Participants Only) | Total |
|---|---|---|---|---|
| Age Continuous | 40.2 years STANDARD_DEVIATION 19.7 | 42.9 years STANDARD_DEVIATION 20.34 | 33.3 years STANDARD_DEVIATION 19.01 | 37.5 years STANDARD_DEVIATION 19.6 |
| Region of Enrollment Canada | 3 participants | 1 participants | 4 participants | 8 participants |
| Region of Enrollment United States | 25 participants | 12 participants | 30 participants | 67 participants |
| Sex: Female, Male Female | 17 Participants | 10 Participants | 21 Participants | 48 Participants |
| Sex: Female, Male Male | 11 Participants | 3 Participants | 13 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 20 / 28 | 33 / 47 |
| serious Total, serious adverse events | 4 / 28 | 10 / 47 |
Outcome results
Primary
Incidence of Cerebrospinal Fluid (CSF) Leakage Observed After Surgery
Study-relevant CSF leakage is defined as one or more of following: 1. Discrete subcutaneous or subgaleal CSF collection (pseudomeningocele) in surgical area confirmed by positive test for β2-transferrin, or by computed tomography (CT) or magnetic resonance imaging (MRI) 2. Epidural CSF collection in surgical area depicted by CT or MRI 3. Leakage of CSF through surgical wound observed during physical examination, confirmed by a positive test for β2-transferrin 4. Progressive pneumatocephalus (air in subarachnoidal space) depicted by repeat CT in absence of CSF drainage.
Time frame: 33 +/- 3 days after surgery
Population: Intent to treat~One participant (SoC arm) received products other than FS VH S/D 500 s-apr for sealing of dura sutures and was removed from analysis~Two participants (FS VH S/D 500 s-apr arm) removed from analysis due to (1) subsequent surgery unrelated to CSF leakage/surgical site infection that involved re-durotomy (2) withdrew from study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard of Care (SoC) | Incidence of Cerebrospinal Fluid (CSF) Leakage Observed After Surgery | 74.07 percentage of participants |
| FS VH S/D 500 S-apr | Incidence of Cerebrospinal Fluid (CSF) Leakage Observed After Surgery | 78.13 percentage of participants |
p-value: 0.7159likelihood ratio of chi squared test
Primary
Number of Participants With Cerebrospinal Fluid (CSF) Leakage Observed After Surgery
Study-relevant CSF leakage is defined as one or more of following: 1. Discrete subcutaneous or subgaleal CSF collection (pseudomeningocele) in surgical area confirmed by positive test for β2-transferrin, or by computed tomography (CT) or magnetic resonance imaging (MRI) 2. Epidural CSF collection in surgical area depicted by CT or MRI 3. Leakage of CSF through surgical wound observed during physical examination, confirmed by a positive test for β2-transferrin 4. Progressive pneumatocephalus (air in subarachnoidal space) depicted by repeat CT in absence of CSF drainage.
Time frame: 33 +/- 3 days after surgery
Population: Intent to treat~One participant (SoC arm) received products other than FS VH S/D 500 s-apr for sealing of dura sutures and was removed from analysis~Two participants (FS VH S/D 500 s-apr arm) removed from analysis due to (1) subsequent surgery unrelated to CSF leakage/surgical site infection that involved re-durotomy (2) withdrew from study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard of Care (SoC) | Number of Participants With Cerebrospinal Fluid (CSF) Leakage Observed After Surgery | 20 participants |
| FS VH S/D 500 S-apr | Number of Participants With Cerebrospinal Fluid (CSF) Leakage Observed After Surgery | 25 participants |
Secondary
Incidence of Procedures Resulting From the Treatment of CSF Leaks
The incidence of surgical revisions, number and duration of compression bandage applications and of liquor drainage procedures
Time frame: until resolution or 30 days after final follow-up visit (Day 33+/-3), whichever is first
Population: Intent to treat~One participant (SoC arm) received products other than FS VH S/D 500 s-apr for sealing of dura sutures and was removed from analysis~One participant (FS VH S/D 500 s-apr arm) removed from analysis due to subsequent surgery unrelated to CSF leakage/surgical site infection that involved re-durotomy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard of Care (SoC) | Incidence of Procedures Resulting From the Treatment of CSF Leaks | Liquor Drainage | 0 percentage of participants |
| Standard of Care (SoC) | Incidence of Procedures Resulting From the Treatment of CSF Leaks | Surgical Revision | 0 percentage of participants |
| Standard of Care (SoC) | Incidence of Procedures Resulting From the Treatment of CSF Leaks | Compression Bandage | 0 percentage of participants |
| FS VH S/D 500 S-apr | Incidence of Procedures Resulting From the Treatment of CSF Leaks | Surgical Revision | 3.03 percentage of participants |
| FS VH S/D 500 S-apr | Incidence of Procedures Resulting From the Treatment of CSF Leaks | Compression Bandage | 0 percentage of participants |
| FS VH S/D 500 S-apr | Incidence of Procedures Resulting From the Treatment of CSF Leaks | Liquor Drainage | 0 percentage of participants |
Secondary
Incidence of Surgical Site Infections (SSI) According to National Nosocomial Infection Surveillance (NNIS) Criteria
Time frame: within 1 month following surgery
Population: Primary Safety Data Set~One participant (FS VH S/D 500 s-apr arm) removed from analysis due to subsequent surgery unrelated to CSF leakage/surgical site infection that involved re-durotomy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard of Care (SoC) | Incidence of Surgical Site Infections (SSI) According to National Nosocomial Infection Surveillance (NNIS) Criteria | 0.00 percentage of participants |
| FS VH S/D 500 S-apr | Incidence of Surgical Site Infections (SSI) According to National Nosocomial Infection Surveillance (NNIS) Criteria | 2.17 percentage of participants |
Secondary
Number of Participants With Procedures Resulting From the Treatment of CSF Leaks
The number of participants with surgical revisions, number and duration of compression bandage applications and of liquor drainage procedures.
Time frame: until resolution or 30 days after final follow-up visit (Day 33+/-3), whichever is first
Population: Intent to treat~One participant (SoC arm) received products other than FS VH S/D 500 s-apr for sealing of dura sutures and was removed from analysis~One participant (FS VH S/D 500 s-apr arm) removed from analysis due to subsequent surgery unrelated to CSF leakage/surgical site infection that involved re-durotomy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard of Care (SoC) | Number of Participants With Procedures Resulting From the Treatment of CSF Leaks | Surgical Revision | 0 participants |
| Standard of Care (SoC) | Number of Participants With Procedures Resulting From the Treatment of CSF Leaks | Compression Bandage | 0 participants |
| Standard of Care (SoC) | Number of Participants With Procedures Resulting From the Treatment of CSF Leaks | Liquor Drainage | 0 participants |
| FS VH S/D 500 S-apr | Number of Participants With Procedures Resulting From the Treatment of CSF Leaks | Compression Bandage | 0 participants |
| FS VH S/D 500 S-apr | Number of Participants With Procedures Resulting From the Treatment of CSF Leaks | Liquor Drainage | 0 participants |
| FS VH S/D 500 S-apr | Number of Participants With Procedures Resulting From the Treatment of CSF Leaks | Surgical Revision | 1 participants |
Secondary
Number of Participants With Surgical Site Infections (SSI) According to National Nosocomial Infection Surveillance (NNIS) Criteria
Time frame: within 1 month following surgery
Population: Primary Safety Data Set~One participant (FS VH S/D 500 s-apr arm) removed from analysis due to subsequent surgery unrelated to CSF leakage/surgical site infection that involved re-durotomy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard of Care (SoC) | Number of Participants With Surgical Site Infections (SSI) According to National Nosocomial Infection Surveillance (NNIS) Criteria | 0 participants |
| FS VH S/D 500 S-apr | Number of Participants With Surgical Site Infections (SSI) According to National Nosocomial Infection Surveillance (NNIS) Criteria | 1 participants |