Trial Outcomes & Findings for Fibrin Sealant for the Sealing of Dura Sutures (NCT NCT00681824)
NCT ID: NCT00681824
Last Updated: 2013-06-27
Results Overview
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.
COMPLETED
PHASE2
95 participants
33 +/- 3 days after surgery
2013-06-27
Participant Flow
Participants were enrolled at 12 United States and 1 Canadian clinical site(s) beginning May 2008 and completing in March 2010
95 were enrolled. 23 discontinued (10 screen failures, 3 withdrawn by investigator, 3 withdrawn by representative or self, 1 died- failure to thrive, 1 had surgery before randomized, 1 study site distance, 1 site reached enrollment goal, 2 patients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.
Participant milestones
| Measure |
Standard of Care
The closure of a dura defect by suturing in a patch of autologous fascia, pericranium or suturable collagen-based dura substitute.
|
Run-in Participants: FS VH S/D 500 S-apr
One initial
|
FS VH S/D 500 S-apr
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.
|
|---|---|---|---|
|
Overall Study
STARTED
|
28
|
13
|
34
|
|
Overall Study
COMPLETED
|
27
|
12
|
33
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
1
|
Reasons for withdrawal
| Measure |
Standard of Care
The closure of a dura defect by suturing in a patch of autologous fascia, pericranium or suturable collagen-based dura substitute.
|
Run-in Participants: FS VH S/D 500 S-apr
One initial
|
FS VH S/D 500 S-apr
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.
|
|---|---|---|---|
|
Overall Study
withdrawn by investigator
|
0
|
0
|
1
|
|
Overall Study
scheduling conflict
|
1
|
0
|
0
|
|
Overall Study
Death
|
0
|
1
|
0
|
Baseline Characteristics
Fibrin Sealant for the Sealing of Dura Sutures
Baseline characteristics by cohort
| Measure |
Standard of Care (SoC)
n=28 Participants
The closure of a dura defect by suturing in a patch of autologous fascia, pericranium or suturable collagen-based dura substitute.
|
FS VH S/D 500 S-apr (Run-In Participants Only)
n=13 Participants
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)
|
FS VH S/D 500 S-apr (Non Run-In Participants Only)
n=34 Participants
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)
|
Total
n=75 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age Continuous
|
40.2 years
STANDARD_DEVIATION 19.7 • n=5 Participants
|
42.9 years
STANDARD_DEVIATION 20.34 • n=7 Participants
|
33.3 years
STANDARD_DEVIATION 19.01 • n=5 Participants
|
37.5 years
STANDARD_DEVIATION 19.6 • n=4 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
48 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
27 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
25 participants
n=5 Participants
|
12 participants
n=7 Participants
|
30 participants
n=5 Participants
|
67 participants
n=4 Participants
|
|
Region of Enrollment
Canada
|
3 participants
n=5 Participants
|
1 participants
n=7 Participants
|
4 participants
n=5 Participants
|
8 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 33 +/- 3 days after surgeryPopulation: 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
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.
Outcome measures
| Measure |
Standard of Care (SoC)
n=27 Participants
The closure of a dura defect by suturing in a patch of autologous fascia, pericranium or suturable collagen-based dura substitute.
|
FS VH S/D 500 S-apr
n=32 Participants
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 13 initial run-in participants (one for each site permitted to familiarize the investigators with the study procedures)
|
|---|---|---|
|
Incidence of Cerebrospinal Fluid (CSF) Leakage Observed After Surgery
|
74.07 percentage of participants
Interval 55.32 to 86.83
|
78.13 percentage of participants
Interval 61.25 to 88.98
|
PRIMARY outcome
Timeframe: 33 +/- 3 days after surgeryPopulation: 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
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.
Outcome measures
| Measure |
Standard of Care (SoC)
n=27 Participants
The closure of a dura defect by suturing in a patch of autologous fascia, pericranium or suturable collagen-based dura substitute.
|
FS VH S/D 500 S-apr
n=32 Participants
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 13 initial run-in participants (one for each site permitted to familiarize the investigators with the study procedures)
|
|---|---|---|
|
Number of Participants With Cerebrospinal Fluid (CSF) Leakage Observed After Surgery
|
20 participants
|
25 participants
|
SECONDARY outcome
Timeframe: until resolution or 30 days after final follow-up visit (Day 33+/-3), whichever is firstPopulation: 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
The incidence of surgical revisions, number and duration of compression bandage applications and of liquor drainage procedures
Outcome measures
| Measure |
Standard of Care (SoC)
n=27 Participants
The closure of a dura defect by suturing in a patch of autologous fascia, pericranium or suturable collagen-based dura substitute.
|
FS VH S/D 500 S-apr
n=33 Participants
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 13 initial run-in participants (one for each site permitted to familiarize the investigators with the study procedures)
|
|---|---|---|
|
Incidence of Procedures Resulting From the Treatment of CSF Leaks
Surgical Revision
|
0 percentage of participants
There were no procedures for this group
|
3.03 percentage of participants
Interval 0.54 to 15.32
|
|
Incidence of Procedures Resulting From the Treatment of CSF Leaks
Compression Bandage
|
0 percentage of participants
There were no procedures for this group
|
0 percentage of participants
There were no procedures for this group
|
|
Incidence of Procedures Resulting From the Treatment of CSF Leaks
Liquor Drainage
|
0 percentage of participants
There were no procedures for this group
|
0 percentage of participants
There were no procedures for this group
|
SECONDARY outcome
Timeframe: until resolution or 30 days after final follow-up visit (Day 33+/-3), whichever is firstPopulation: 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
The number of participants with surgical revisions, number and duration of compression bandage applications and of liquor drainage procedures.
Outcome measures
| Measure |
Standard of Care (SoC)
n=27 Participants
The closure of a dura defect by suturing in a patch of autologous fascia, pericranium or suturable collagen-based dura substitute.
|
FS VH S/D 500 S-apr
n=33 Participants
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 13 initial run-in participants (one for each site permitted to familiarize the investigators with the study procedures)
|
|---|---|---|
|
Number of Participants With Procedures Resulting From the Treatment of CSF Leaks
Surgical Revision
|
0 participants
|
1 participants
Interval 0.54 to 15.32
|
|
Number of Participants With Procedures Resulting From the Treatment of CSF Leaks
Compression Bandage
|
0 participants
|
0 participants
|
|
Number of Participants With Procedures Resulting From the Treatment of CSF Leaks
Liquor Drainage
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: within 1 month following surgeryPopulation: 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
Outcome measures
| Measure |
Standard of Care (SoC)
n=28 Participants
The closure of a dura defect by suturing in a patch of autologous fascia, pericranium or suturable collagen-based dura substitute.
|
FS VH S/D 500 S-apr
n=46 Participants
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 13 initial run-in participants (one for each site permitted to familiarize the investigators with the study procedures)
|
|---|---|---|
|
Incidence of Surgical Site Infections (SSI) According to National Nosocomial Infection Surveillance (NNIS) Criteria
|
0.00 percentage of participants
There were no SSIs for this group
|
2.17 percentage of participants
Interval 0.38 to 11.34
|
SECONDARY outcome
Timeframe: within 1 month following surgeryPopulation: 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
Outcome measures
| Measure |
Standard of Care (SoC)
n=28 Participants
The closure of a dura defect by suturing in a patch of autologous fascia, pericranium or suturable collagen-based dura substitute.
|
FS VH S/D 500 S-apr
n=46 Participants
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 13 initial run-in participants (one for each site permitted to familiarize the investigators with the study procedures)
|
|---|---|---|
|
Number of Participants With Surgical Site Infections (SSI) According to National Nosocomial Infection Surveillance (NNIS) Criteria
|
0 participants
|
1 participants
Interval 0.38 to 11.34
|
Adverse Events
Standard of Care (SoC)
FS VH S/D 500 S-apr
Serious adverse events
| Measure |
Standard of Care (SoC)
n=28 participants at risk
The closure of a dura defect by suturing in a patch of autologous fascia, pericranium or suturable collagen-based dura substitute.
|
FS VH S/D 500 S-apr
n=47 participants at risk
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 includes 13 initial "run-in" participants (one for each site permitted to familiarize the investigators with the study procedures)
|
|---|---|---|
|
Injury, poisoning and procedural complications
Intracranial hypotension
|
0.00%
0/28 • Throughout the study period, 1 year and 10 months
|
4.3%
2/47 • Number of events 2 • Throughout the study period, 1 year and 10 months
|
|
Injury, poisoning and procedural complications
Post procedural complication
|
0.00%
0/28 • Throughout the study period, 1 year and 10 months
|
2.1%
1/47 • Number of events 1 • Throughout the study period, 1 year and 10 months
|
|
Injury, poisoning and procedural complications
Pseudomeningocele
|
0.00%
0/28 • Throughout the study period, 1 year and 10 months
|
4.3%
2/47 • Number of events 2 • Throughout the study period, 1 year and 10 months
|
|
Metabolism and nutrition disorders
Failure to thrive
|
0.00%
0/28 • Throughout the study period, 1 year and 10 months
|
2.1%
1/47 • Number of events 1 • Throughout the study period, 1 year and 10 months
|
|
Nervous system disorders
Cerebellar haemorrhage
|
0.00%
0/28 • Throughout the study period, 1 year and 10 months
|
2.1%
1/47 • Number of events 1 • Throughout the study period, 1 year and 10 months
|
|
Nervous system disorders
Hydrocephalus
|
0.00%
0/28 • Throughout the study period, 1 year and 10 months
|
4.3%
2/47 • Number of events 2 • Throughout the study period, 1 year and 10 months
|
|
Nervous system disorders
Meningitis aseptic
|
0.00%
0/28 • Throughout the study period, 1 year and 10 months
|
2.1%
1/47 • Number of events 1 • Throughout the study period, 1 year and 10 months
|
|
Psychiatric disorders
Affect lability
|
0.00%
0/28 • Throughout the study period, 1 year and 10 months
|
2.1%
1/47 • Number of events 1 • Throughout the study period, 1 year and 10 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/28 • Throughout the study period, 1 year and 10 months
|
2.1%
1/47 • Number of events 1 • Throughout the study period, 1 year and 10 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/28 • Throughout the study period, 1 year and 10 months
|
2.1%
1/47 • Number of events 1 • Throughout the study period, 1 year and 10 months
|
|
Vascular disorders
Deep vein thrombosis
|
3.6%
1/28 • Number of events 1 • Throughout the study period, 1 year and 10 months
|
2.1%
1/47 • Number of events 1 • Throughout the study period, 1 year and 10 months
|
|
General disorders
Facial pain
|
3.6%
1/28 • Number of events 1 • Throughout the study period, 1 year and 10 months
|
0.00%
0/47 • Throughout the study period, 1 year and 10 months
|
|
Psychiatric disorders
Mental status changes
|
3.6%
1/28 • Number of events 1 • Throughout the study period, 1 year and 10 months
|
0.00%
0/47 • Throughout the study period, 1 year and 10 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
3.6%
1/28 • Number of events 1 • Throughout the study period, 1 year and 10 months
|
0.00%
0/47 • Throughout the study period, 1 year and 10 months
|
Other adverse events
| Measure |
Standard of Care (SoC)
n=28 participants at risk
The closure of a dura defect by suturing in a patch of autologous fascia, pericranium or suturable collagen-based dura substitute.
|
FS VH S/D 500 S-apr
n=47 participants at risk
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 includes 13 initial "run-in" participants (one for each site permitted to familiarize the investigators with the study procedures)
|
|---|---|---|
|
Eye disorders
Diplopia
|
10.7%
3/28 • Number of events 3 • Throughout the study period, 1 year and 10 months
|
0.00%
0/47 • Throughout the study period, 1 year and 10 months
|
|
Gastrointestinal disorders
Nausea
|
21.4%
6/28 • Number of events 6 • Throughout the study period, 1 year and 10 months
|
10.6%
5/47 • Number of events 5 • Throughout the study period, 1 year and 10 months
|
|
Gastrointestinal disorders
Vomiting
|
10.7%
3/28 • Number of events 3 • Throughout the study period, 1 year and 10 months
|
4.3%
2/47 • Number of events 2 • Throughout the study period, 1 year and 10 months
|
|
General disorders
Pyrexia
|
0.00%
0/28 • Throughout the study period, 1 year and 10 months
|
10.6%
5/47 • Number of events 5 • Throughout the study period, 1 year and 10 months
|
|
Infections and infestations
Candidiasis
|
7.1%
2/28 • Number of events 2 • Throughout the study period, 1 year and 10 months
|
0.00%
0/47 • Throughout the study period, 1 year and 10 months
|
|
Infections and infestations
Urinary tract infection
|
3.6%
1/28 • Number of events 1 • Throughout the study period, 1 year and 10 months
|
6.4%
3/47 • Number of events 3 • Throughout the study period, 1 year and 10 months
|
|
Injury, poisoning and procedural complications
Incision site pain
|
53.6%
15/28 • Number of events 15 • Throughout the study period, 1 year and 10 months
|
53.2%
25/47 • Number of events 25 • Throughout the study period, 1 year and 10 months
|
|
Injury, poisoning and procedural complications
Pseudomeningocele
|
7.1%
2/28 • Number of events 2 • Throughout the study period, 1 year and 10 months
|
2.1%
1/47 • Number of events 1 • Throughout the study period, 1 year and 10 months
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
7.1%
2/28 • Number of events 2 • Throughout the study period, 1 year and 10 months
|
2.1%
1/47 • Number of events 1 • Throughout the study period, 1 year and 10 months
|
|
Nervous system disorders
Balance disorder
|
7.1%
2/28 • Number of events 2 • Throughout the study period, 1 year and 10 months
|
0.00%
0/47 • Throughout the study period, 1 year and 10 months
|
|
Nervous system disorders
Headache
|
3.6%
1/28 • Number of events 2 • Throughout the study period, 1 year and 10 months
|
8.5%
4/47 • Number of events 4 • Throughout the study period, 1 year and 10 months
|
|
Vascular disorders
Hypertension
|
7.1%
2/28 • Number of events 2 • Throughout the study period, 1 year and 10 months
|
10.6%
5/47 • Number of events 5 • Throughout the study period, 1 year and 10 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Baxter's agreements with PIs may vary per requirements of individual PI, but contain common elements. For this study, PIs are restricted from independently publishing results until the earlier of the primary multicenter publication or 12 months after study completion. Baxter requires a review of results communications (e.g., for confidential information) ≥45 days prior to submission or communication. Baxter may request an additional delay of ≤60 days e.g., for intellectual property protection)
- Publication restrictions are in place
Restriction type: OTHER