Elective Cranial Procedures With Dural Incision
Conditions
Keywords
Adherus Dural Sealant, Adherus AutoSpray Dural Sealant
Brief summary
The purpose of the study is to demonstrate the safety and effectiveness of the Adherus Dural Sealant System when used as a dural sealant in conjunction with standard methods of dural repair in cranial procedures.
Detailed description
After surgery on the head, the dura, a membrane that covers the brain, must be closed in order to prevent CSF from leaking outside of the dura. When CSF leaks outside the dura, this can increase the risk of infection, cause painful headaches or complications that may require another surgery to repair the leak. Typically, your study doctor will close the dura with sutures (surgical stitches) and sometimes a piece of muscle, fat, or other soft tissue taken from another place on your body. However, it is still possible that CSF will continue to leak through small suture holes even when all appropriate precautions have been taken. Dural surgical sealants have been developed to assist surgeons in stopping CSF leaks when standard measures following brain surgery are not effective. Sometimes, the leak seals on its own and there is no need for a surgical sealant. This study is for participants who have a CSF leak after standard measures are used to close the dura at the end of their surgery. The decision to use a surgical sealant will be made when your surgeon finds that after stitching and using standard measures to close the dura, there is still a leak. However, if your surgeon finds a CSF leak after he or she applies the standard stitches and tissues, and you have signed this informed consent, then you will be randomized to receive one of two surgical sealants (Randomized means like a flip of the coin). You will be selected to receive either Adherus™ Surgical Sealant or DuraSeal™ Surgical Sealant and your post surgery progress will be evaluated during study visits and with study tests. Adherus™ Surgical Sealant is an investigational device that has been developed to stop CSF leaks. It is being studied to find if it is just as effective and safe as DuraSeal™. Adherus™ is made of two components that form a gel when they are combined. The gel is applied after the study doctor closes the incision. The gel acts as a thin, elastic barrier intended to prevent CSF from leaking until the dura tissue has properly healed on its own. The gel is then absorbed by the body over several months and excreted or removed from the body through the urine. This is the second study of Adherus™ in people in the United States. If you choose to participate, you will have screening tests to see if you qualify to enroll in the study. Not everyone who is screened for the study will be able to participate. The device you receive will be determined by a random selection process. Neither you nor study personnel or your doctor can decide which device you receive. You will not be told which device you received until study completion. In addition, if your study doctor does not use any sealant at the end of your surgery (you may not have any CSF leak or the study doctor decides to use another closure procedure) then your study participation will be complete. If you choose to participate and have screening tests to qualify you to enroll in the study, your surgery will be performed according to the regular standard of care. If CSF leaks from your dura after it is stitched closed by your study doctor and you continue to meet study entry measures, then your study doctor will apply the assigned study treatment to try to stop the leak. After the surgery, you will be seen 4 times over the next 4 months. You will be in the study for up to 5 months.
Interventions
DEVICEAdherus Dural Sealant
In situ polymerizing sealant
Sponsors
HyperBranch Medical Technology, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Pre-Operative Inclusion Criteria * Subject is scheduled for an elective cranial procedure involving a dural incision using any of the following surgical locations/approaches (or combination): frontal, temporal, occipital, and parietal (i.e. supratentorial), and/or midline or lateral suboccipital (i.e. infratentorial.) Subject requires a procedure involving a Class 1/clean wound (uninfected surgical wound in which no inflammation is encountered) Intra-Operative Inclusion Criteria * Subject's linear extent of durotomy is ≥2 cm * Subject's dural margins from the edges of bony defect are ≥3 mm throughout * Subject's CSF leak is present intra-operatively following completion of primary dural closure (with or without non-autologous duraplasty or autologous tissue), either spontaneously or upon Valsalva maneuver, at up to 20 cm H2O for up to five (5) seconds
Exclusion criteria
* Subject requires a procedure involving a translabyrinthine, transsphenoidal, transoral approach, or any procedure that penetrates the air sinus or mastoid air cells. Note: Superficial penetration of mastoid air cells is not an exclusion if cells are appropriately sealed (e.g. bone wax). * Subject has a CSF shunt such as; ventriculo-peritoneal, ventriculo-pleural, ventriculo-atrial or lumbo-peritoneal shunts. * Subject has an external ventricular or lumbar CSF drain that must be left in place after surgery. * Subject has had radiation treatment to the surgical site, or standard fractionated radiation therapy is planned within ten days post index-procedure. (Note: stereotactic radiosurgery prior to the planned index procedure is not an exclusion criterion). * Subject has a systemic infection or evidence of any infection near planned operative site. Intra-Operative
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Treated Subjects Who Were Free of Intra-operative Cerebrospinal Fluid (CSF) Leakage From Dural Repair During Valsalva Maneuver, CSF Leak / Pseudomeningocele, and Unplanned Retreatment of the Original Surgical Site | 120 days | The primary endpoint was a composite evaluation of the safety and effectiveness of Adherus for a cranial application. The endpoint was measured by the proportion of treated subjects who were free of all of the following incidences: * Intra-operative CSF leakage from dural repair after up to two Adherus / control applications during Valsalva maneuver up to 20cm H2O for up to 5 seconds. * CSF leak or pseudomeningocele diagnosed by physical examination, biochemical assay or imaging study during the 120-day follow-up period of the index procedure * Unplanned retreatment of the original surgical site adjudicated by the CEC to be device-related, including meningitis or the management of deep infection, minimally invasive procedures or return to the operating room for neurosurgical complications other than CSF leak or pseudomeningocele formation or those related to the subject's pre-existing condition, during the 120-day follow-up period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Free of Device-related Surgical Wound Infections or Meningitis During 120-day Follow-up. | 120 days | Device-related surgical wound infections included all infections classified by the CEC as definitely, probably, possibly or undetermined in relation to the device. |
Countries
United States
Participant flow
Recruitment details
The first subject was treated on September 3, 2010 and the last subject visit occurred on January 17, 2013.
Pre-assignment details
Randomized study, no washout or run-in period.
Participants by arm
| Arm | Count |
|---|---|
| Adherus Dural Sealant Adherus Dural Sealant: In situ polymerizing sealant | 120 |
| DuraSeal Dural Sealant System DuraSeal Dural Sealant System: In situ polymerizing sealant | 122 |
| Total | 242 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 4 | 5 |
| Overall Study | Lost to Follow-up | 2 | 4 |
| Overall Study | Withdrawal by Subject | 4 | 0 |
Baseline characteristics
| Characteristic | Adherus Dural Sealant | DuraSeal Dural Sealant System | Total |
|---|---|---|---|
| Age, Customized | 51.1 years STANDARD_DEVIATION 14 | 49.6 years STANDARD_DEVIATION 15.1 | 50.4 years STANDARD_DEVIATION 15.1 |
| Region of Enrollment United States | 120 participants | 122 participants | 242 participants |
| Sex: Female, Male Female | 41 Participants | 38 Participants | 79 Participants |
| Sex: Female, Male Male | 79 Participants | 84 Participants | 163 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 28 / 124 | 29 / 126 |
| serious Total, serious adverse events | 33 / 124 | 33 / 126 |
Outcome results
Primary
Proportion of Treated Subjects Who Were Free of Intra-operative Cerebrospinal Fluid (CSF) Leakage From Dural Repair During Valsalva Maneuver, CSF Leak / Pseudomeningocele, and Unplanned Retreatment of the Original Surgical Site
The primary endpoint was a composite evaluation of the safety and effectiveness of Adherus for a cranial application. The endpoint was measured by the proportion of treated subjects who were free of all of the following incidences: * Intra-operative CSF leakage from dural repair after up to two Adherus / control applications during Valsalva maneuver up to 20cm H2O for up to 5 seconds. * CSF leak or pseudomeningocele diagnosed by physical examination, biochemical assay or imaging study during the 120-day follow-up period of the index procedure * Unplanned retreatment of the original surgical site adjudicated by the CEC to be device-related, including meningitis or the management of deep infection, minimally invasive procedures or return to the operating room for neurosurgical complications other than CSF leak or pseudomeningocele formation or those related to the subject's pre-existing condition, during the 120-day follow-up period.
Time frame: 120 days
Population: All subjects who received treatment with evaluable 120-day follow-up data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adherus Dural Sealant System | Proportion of Treated Subjects Who Were Free of Intra-operative Cerebrospinal Fluid (CSF) Leakage From Dural Repair During Valsalva Maneuver, CSF Leak / Pseudomeningocele, and Unplanned Retreatment of the Original Surgical Site | 91.2 percentage of subjects |
| DuraSeal Dural Sealant System | Proportion of Treated Subjects Who Were Free of Intra-operative Cerebrospinal Fluid (CSF) Leakage From Dural Repair During Valsalva Maneuver, CSF Leak / Pseudomeningocele, and Unplanned Retreatment of the Original Surgical Site | 90.6 percentage of subjects |
p-value: 0.0049one-sided z-test
Secondary
Proportion of Subjects Free of Device-related Surgical Wound Infections or Meningitis During 120-day Follow-up.
Device-related surgical wound infections included all infections classified by the CEC as definitely, probably, possibly or undetermined in relation to the device.
Time frame: 120 days
Population: Includes all subjects with available data that through 120 days follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adherus Dural Sealant System | Proportion of Subjects Free of Device-related Surgical Wound Infections or Meningitis During 120-day Follow-up. | 100 percentage of subjects |
| DuraSeal Dural Sealant System | Proportion of Subjects Free of Device-related Surgical Wound Infections or Meningitis During 120-day Follow-up. | 98.3 percentage of subjects |
Post Hoc
Proportion of Treated Subjects Who Were Free of Intra-operative Cerebrospinal Fluid (CSF) Leakage From Dural Repair During Valsalva Maneuver, CSF Leak / Pseudomeningocele, and Unplanned Retreatment of the Original Surgical Site
Post-Hoc analysis of primary composite endpoint of the safety and effectiveness of Adherus for a cranial application at 14 days. The endpoint was measured by the proportion of treated subjects who were free of all of the following incidences: * Intra-operative CSF leakage from dural repair after up to two Adherus / control applications during Valsalva maneuver up to 20cm H2O for up to 5 seconds. * CSF leak or pseudomeningocele diagnosed by physical examination, biochemical assay or imaging study during the 120-day follow-up period of the index procedure * Unplanned retreatment of the original surgical site adjudicated by the CEC to be device-related, including meningitis or the management of deep infection, minimally invasive procedures or return to the operating room for neurosurgical complications other than CSF leak or pseudomeningocele formation or those related to the subject's pre-existing condition, during the 120-day follow-up period.
Time frame: 14 days
Population: All subjects who received treatment with evaluable 14-day follow-up data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adherus Dural Sealant System | Proportion of Treated Subjects Who Were Free of Intra-operative Cerebrospinal Fluid (CSF) Leakage From Dural Repair During Valsalva Maneuver, CSF Leak / Pseudomeningocele, and Unplanned Retreatment of the Original Surgical Site | 99.1 percentage of subjects |
| DuraSeal Dural Sealant System | Proportion of Treated Subjects Who Were Free of Intra-operative Cerebrospinal Fluid (CSF) Leakage From Dural Repair During Valsalva Maneuver, CSF Leak / Pseudomeningocele, and Unplanned Retreatment of the Original Surgical Site | 95.0 percentage of subjects |
p-value: <0.0001one-sided z-test
Comparison: Superiority Testp-value: 0.0297one-sided z-test
Post Hoc
Proportion of Treated Subjects Who Were Free of Intra-operative Cerebrospinal Fluid (CSF) Leakage From Dural Repair During Valsalva Maneuver, CSF Leak / Pseudomeningocele, and Unplanned Retreatment of the Original Surgical Site
Post-Hoc analysis of primary composite endpoint of the safety and effectiveness of Adherus for a cranial application at 45 days. The endpoint was measured by the proportion of treated subjects who were free of all of the following incidences: * Intra-operative CSF leakage from dural repair after up to two Adherus / control applications during Valsalva maneuver up to 20cm H2O for up to 5 seconds. * CSF leak or pseudomeningocele diagnosed by physical examination, biochemical assay or imaging study during the 120-day follow-up period of the index procedure * Unplanned retreatment of the original surgical site adjudicated by the CEC to be device-related, including meningitis or the management of deep infection, minimally invasive procedures or return to the operating room for neurosurgical complications other than CSF leak or pseudomeningocele formation or those related to the subject's pre-existing condition, during the 120-day follow-up period.
Time frame: 45 days
Population: All subjects who received treatment with evaluable 45-day follow-up data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adherus Dural Sealant System | Proportion of Treated Subjects Who Were Free of Intra-operative Cerebrospinal Fluid (CSF) Leakage From Dural Repair During Valsalva Maneuver, CSF Leak / Pseudomeningocele, and Unplanned Retreatment of the Original Surgical Site | 96.6 percentage of subjects |
| DuraSeal Dural Sealant System | Proportion of Treated Subjects Who Were Free of Intra-operative Cerebrospinal Fluid (CSF) Leakage From Dural Repair During Valsalva Maneuver, CSF Leak / Pseudomeningocele, and Unplanned Retreatment of the Original Surgical Site | 91.9 percentage of subjects |
p-value: <0.0001one-sided z-test
Comparison: Superiority Testp-value: 0.0561one-sided z-test