Trial Outcomes & Findings for Efficacy and Safety of FS VH S/D 500 S-apr (Tisseel) as an Adjunct to Sutured Dural Repair in Cranial Surgery (NCT NCT02891070)

Last Updated: 2019-09-10

Results Overview

Participants who have no intra-operative CSF leak from dural repair after up to two applications during Valsalva maneuver (25 cm H2O for up to 5 - 10 seconds), or post-operative CSF leak within 30 (+3) days post-operatively. The Valsalva maneuver was performed by the anaesthesiologist to increase the intra-thoracic pressure (e.g., by increasing the positive end-expiratory pressure or by giving a large tidal volume and holding the inflating pressure) to approximately 25 cm H2O, constantly for up to 5 - 10 seconds to transiently elevate the intracranial pressure and test for any CSF leaks. The suture line was to be watertight after up to two product/control applications and Valsalva maneuvers.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

224 participants

Primary outcome timeframe

Day 0 (Intra-operative) to Day 30 (+/-3 days) post-operative

Results posted on

2019-09-10

Participant Flow

Participant milestones

Participant milestones
Measure	Tisseel Tisseel (FS VH S/D 500 s-apr), single use treatment, was administered intra-operatively with sutures during dural closure. Product was applied with cannula by dripping in a thin and continuous layer with a 5 mm overlap on each side of the sutured line, ensuring that all suture holes were covered.	DuraSeal DuraSeal Dural Sealant, single use treatment, was administered intra-operatively with sutures during dural closure. The product was applied with the DuraSeal System Applicator by spraying a thin (1 - 2 mm) coating, ensuring that all suture holes were covered.
Overall Study STARTED	110	114
Overall Study COMPLETED	100	106
Overall Study NOT COMPLETED	10	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Tisseel Tisseel (FS VH S/D 500 s-apr), single use treatment, was administered intra-operatively with sutures during dural closure. Product was applied with cannula by dripping in a thin and continuous layer with a 5 mm overlap on each side of the sutured line, ensuring that all suture holes were covered.	DuraSeal DuraSeal Dural Sealant, single use treatment, was administered intra-operatively with sutures during dural closure. The product was applied with the DuraSeal System Applicator by spraying a thin (1 - 2 mm) coating, ensuring that all suture holes were covered.
Overall Study Adverse Event	1	0
Overall Study Physician Decision	0	1
Overall Study Lost to Follow-up	4	4
Overall Study Other	1	0
Overall Study Protocol Violation	0	1
Overall Study Withdrawal by Subject	1	2
Overall Study Death	3	0

Baseline Characteristics

Efficacy and Safety of FS VH S/D 500 S-apr (Tisseel) as an Adjunct to Sutured Dural Repair in Cranial Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tisseel n=110 Participants Tisseel (FS VH S/D 500 s-apr), single use treatment, was administered intra-operatively with sutures during dural closure. Product was applied with cannula by dripping in a thin and continuous layer with a 5 mm overlap on each side of the sutured line, ensuring that all suture holes were covered.	DuraSeal n=114 Participants DuraSeal Dural Sealant, single use treatment, was administered intra-operatively with sutures during dural closure. The product was applied with the DuraSeal System Applicator by spraying a thin (1 - 2 mm) coating, ensuring that all suture holes were covered.	Total n=224 Participants Total of all reporting groups
Age, Continuous	51.8 Years STANDARD_DEVIATION 14.24 • n=99 Participants	51.3 Years STANDARD_DEVIATION 14.85 • n=107 Participants	51.5 Years STANDARD_DEVIATION 14.53 • n=206 Participants
Sex: Female, Male Female	66 Participants n=99 Participants	65 Participants n=107 Participants	131 Participants n=206 Participants
Sex: Female, Male Male	44 Participants n=99 Participants	49 Participants n=107 Participants	93 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	2 Participants n=99 Participants	2 Participants n=107 Participants	4 Participants n=206 Participants
Race (NIH/OMB) White	97 Participants n=99 Participants	101 Participants n=107 Participants	198 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	11 Participants n=99 Participants	11 Participants n=107 Participants	22 Participants n=206 Participants

PRIMARY outcome

Timeframe: Day 0 (Intra-operative) to Day 30 (+/-3 days) post-operative

Population: Per-protocol analysis set (PPS): The PPS was defined as a subset of the FAS. Patients with any major deviation that may have impacted the primary efficacy parameter were excluded from the PPS.

Outcome measures

Outcome measures
Measure	Tisseel n=89 Participants Tisseel (FS VH S/D 500 s-apr), single use treatment, was administered intra-operatively with sutures during dural closure. Product was applied with cannula by dripping in a thin and continuous layer with a 5 mm overlap on each side of the sutured line, ensuring that all suture holes were covered.	DuraSeal n=95 Participants DuraSeal Dural Sealant, single use treatment, was administered intra-operatively with sutures during dural closure. The product was applied with the DuraSeal System Applicator by spraying a thin (1 - 2 mm) coating, ensuring that all suture holes were covered.
Number of Participants With No CSF Leak During and After Surgery	76 Participants	87 Participants

SECONDARY outcome

Timeframe: Day 0 (Intra-operative)

Assessment of whether the suture line was not watertight causing CSF leaks after up to two product/control applications and Valsalva maneuvers.

Outcome measures

Outcome measures
Measure	Tisseel n=89 Participants Tisseel (FS VH S/D 500 s-apr), single use treatment, was administered intra-operatively with sutures during dural closure. Product was applied with cannula by dripping in a thin and continuous layer with a 5 mm overlap on each side of the sutured line, ensuring that all suture holes were covered.	DuraSeal n=95 Participants DuraSeal Dural Sealant, single use treatment, was administered intra-operatively with sutures during dural closure. The product was applied with the DuraSeal System Applicator by spraying a thin (1 - 2 mm) coating, ensuring that all suture holes were covered.
Number of Participants With no Intra-operative CSF Leaks Following Final Valsalva Maneuver	89 Participants	95 Participants

SECONDARY outcome

Timeframe: Day 0 (Intra-operative) to Day 30 (+/-3 days) post-operative

Cerebrospinal fluid leak was defined as any overt flow, seepage, weeping, or sweating of CSF through the dura suture line, regardless of volume. All post-operative CSF leaks were primarily diagnosed based on a detailed history and physical examination, including neurological examination. Although not standard of care post-operatively, imaging tests such as computed tomography/magnetic resonance imaging (MRI) were considered if there was a high clinical suspicion of a CSF leak.

Outcome measures

Outcome measures
Measure	Tisseel n=89 Participants Tisseel (FS VH S/D 500 s-apr), single use treatment, was administered intra-operatively with sutures during dural closure. Product was applied with cannula by dripping in a thin and continuous layer with a 5 mm overlap on each side of the sutured line, ensuring that all suture holes were covered.	DuraSeal n=95 Participants DuraSeal Dural Sealant, single use treatment, was administered intra-operatively with sutures during dural closure. The product was applied with the DuraSeal System Applicator by spraying a thin (1 - 2 mm) coating, ensuring that all suture holes were covered.
Number of Participants With CSF Leaks Within 30 (+3) Days Post-operatively	8 Participants	2 Participants

SECONDARY outcome

Timeframe: Day 0 (intra-operatively)

Patients undergoing elective cranial surgery for the treatment of a pathological condition (e.g., benign/malignant tumours, vascular malformations, or Chiari type 1 malformations) specifically located in the posterior fossa (PF) or supratentorial (ST) regions.

Outcome measures

Outcome measures
Measure	Tisseel n=89 Participants Tisseel (FS VH S/D 500 s-apr), single use treatment, was administered intra-operatively with sutures during dural closure. Product was applied with cannula by dripping in a thin and continuous layer with a 5 mm overlap on each side of the sutured line, ensuring that all suture holes were covered.	DuraSeal n=95 Participants DuraSeal Dural Sealant, single use treatment, was administered intra-operatively with sutures during dural closure. The product was applied with the DuraSeal System Applicator by spraying a thin (1 - 2 mm) coating, ensuring that all suture holes were covered.
Duration in Surgery (Minutes)	241.8 Minutes Standard Deviation 100.80	210.3 Minutes Standard Deviation 90.49

SECONDARY outcome

Timeframe: Day 0 (Intra-operatively)

Suture closure techniques include continuous simple, continuous locked, interrupted.

Outcome measures

Outcome measures
Measure	Tisseel n=89 Participants Tisseel (FS VH S/D 500 s-apr), single use treatment, was administered intra-operatively with sutures during dural closure. Product was applied with cannula by dripping in a thin and continuous layer with a 5 mm overlap on each side of the sutured line, ensuring that all suture holes were covered.	DuraSeal n=95 Participants DuraSeal Dural Sealant, single use treatment, was administered intra-operatively with sutures during dural closure. The product was applied with the DuraSeal System Applicator by spraying a thin (1 - 2 mm) coating, ensuring that all suture holes were covered.
Time From Dural Closure (Application of IP) Until End of Surgery	34 Minutes Standard Deviation 16.13	31.4 Minutes Standard Deviation 17.07

SECONDARY outcome

Timeframe: Day 0 to Day 60 (Study Completion)

Days in hospital calculation is Day 0 - Discharge.

Outcome measures

Outcome measures
Measure	Tisseel n=89 Participants Tisseel (FS VH S/D 500 s-apr), single use treatment, was administered intra-operatively with sutures during dural closure. Product was applied with cannula by dripping in a thin and continuous layer with a 5 mm overlap on each side of the sutured line, ensuring that all suture holes were covered.	DuraSeal n=95 Participants DuraSeal Dural Sealant, single use treatment, was administered intra-operatively with sutures during dural closure. The product was applied with the DuraSeal System Applicator by spraying a thin (1 - 2 mm) coating, ensuring that all suture holes were covered.
Length of Stay in Hospital (Days).	13.5 Days Standard Deviation 15.57	12.6 Days Standard Deviation 8.67

POST_HOC outcome

Timeframe: Day 0 (Intra-operative) to Day 30 (+/-3 days) post-operative

Population: Safety analysis set (SAS): The SAS consisted of all patients who were treated with IP/Control. Patients were analyzed as treated.

Surgical site infections were evaluated by the surgeon or designated physician according to United States (US) National Healthcare Safety Network (NHSN) criteria as specified in the study protocol.

Outcome measures

Outcome measures
Measure	Tisseel n=110 Participants Tisseel (FS VH S/D 500 s-apr), single use treatment, was administered intra-operatively with sutures during dural closure. Product was applied with cannula by dripping in a thin and continuous layer with a 5 mm overlap on each side of the sutured line, ensuring that all suture holes were covered.	DuraSeal n=114 Participants DuraSeal Dural Sealant, single use treatment, was administered intra-operatively with sutures during dural closure. The product was applied with the DuraSeal System Applicator by spraying a thin (1 - 2 mm) coating, ensuring that all suture holes were covered.
Number of Surgical Site Infections (SSI)	1 SSI	4 SSI

Adverse Events

Tisseel

Serious events: 22 serious events

Other events: 46 other events

Deaths: 3 deaths

DuraSeal

Serious events: 17 serious events

Other events: 46 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Tisseel n=110 participants at risk Tisseel (FS VH S/D 500 s-apr), single use treatment, was administered intra-operatively with sutures during dural closure. Product was applied with cannula by dripping in a thin and continuous layer with a 5 mm overlap on each side of the sutured line, ensuring that all suture holes were covered.	DuraSeal n=114 participants at risk DuraSeal Dural Sealant, single use treatment, was administered intra-operatively with sutures during dural closure. The product was applied with the DuraSeal System Applicator by spraying a thin (1 - 2 mm) coating, ensuring that all suture holes were covered.
Gastrointestinal disorders Constipation	7.3% 8/110 • Number of events 9 • Day -30 (Pre-operative) to Day 60 (+/- 3 days) Treatment-Emergent Adverse Events (TEAE) were reported for both Adverse Event (AE) and Serious Adverse Events (SAE). TEAE's are events that began or worsen in severity after the first administration of treatment.	4.4% 5/114 • Number of events 5 • Day -30 (Pre-operative) to Day 60 (+/- 3 days) Treatment-Emergent Adverse Events (TEAE) were reported for both Adverse Event (AE) and Serious Adverse Events (SAE). TEAE's are events that began or worsen in severity after the first administration of treatment.
Gastrointestinal disorders Nausea	9.1% 10/110 • Number of events 12 • Day -30 (Pre-operative) to Day 60 (+/- 3 days) Treatment-Emergent Adverse Events (TEAE) were reported for both Adverse Event (AE) and Serious Adverse Events (SAE). TEAE's are events that began or worsen in severity after the first administration of treatment.	12.3% 14/114 • Number of events 16 • Day -30 (Pre-operative) to Day 60 (+/- 3 days) Treatment-Emergent Adverse Events (TEAE) were reported for both Adverse Event (AE) and Serious Adverse Events (SAE). TEAE's are events that began or worsen in severity after the first administration of treatment.
Gastrointestinal disorders Vomiting	9.1% 10/110 • Number of events 15 • Day -30 (Pre-operative) to Day 60 (+/- 3 days) Treatment-Emergent Adverse Events (TEAE) were reported for both Adverse Event (AE) and Serious Adverse Events (SAE). TEAE's are events that began or worsen in severity after the first administration of treatment.	12.3% 14/114 • Number of events 17 • Day -30 (Pre-operative) to Day 60 (+/- 3 days) Treatment-Emergent Adverse Events (TEAE) were reported for both Adverse Event (AE) and Serious Adverse Events (SAE). TEAE's are events that began or worsen in severity after the first administration of treatment.
General disorders Pain	13.6% 15/110 • Number of events 15 • Day -30 (Pre-operative) to Day 60 (+/- 3 days) Treatment-Emergent Adverse Events (TEAE) were reported for both Adverse Event (AE) and Serious Adverse Events (SAE). TEAE's are events that began or worsen in severity after the first administration of treatment.	13.2% 15/114 • Number of events 16 • Day -30 (Pre-operative) to Day 60 (+/- 3 days) Treatment-Emergent Adverse Events (TEAE) were reported for both Adverse Event (AE) and Serious Adverse Events (SAE). TEAE's are events that began or worsen in severity after the first administration of treatment.
General disorders Pyrexia	2.7% 3/110 • Number of events 6 • Day -30 (Pre-operative) to Day 60 (+/- 3 days) Treatment-Emergent Adverse Events (TEAE) were reported for both Adverse Event (AE) and Serious Adverse Events (SAE). TEAE's are events that began or worsen in severity after the first administration of treatment.	6.1% 7/114 • Number of events 7 • Day -30 (Pre-operative) to Day 60 (+/- 3 days) Treatment-Emergent Adverse Events (TEAE) were reported for both Adverse Event (AE) and Serious Adverse Events (SAE). TEAE's are events that began or worsen in severity after the first administration of treatment.
Nervous system disorders Dizziness	5.5% 6/110 • Number of events 8 • Day -30 (Pre-operative) to Day 60 (+/- 3 days) Treatment-Emergent Adverse Events (TEAE) were reported for both Adverse Event (AE) and Serious Adverse Events (SAE). TEAE's are events that began or worsen in severity after the first administration of treatment.	2.6% 3/114 • Number of events 4 • Day -30 (Pre-operative) to Day 60 (+/- 3 days) Treatment-Emergent Adverse Events (TEAE) were reported for both Adverse Event (AE) and Serious Adverse Events (SAE). TEAE's are events that began or worsen in severity after the first administration of treatment.
Nervous system disorders Headache	18.2% 20/110 • Number of events 25 • Day -30 (Pre-operative) to Day 60 (+/- 3 days) Treatment-Emergent Adverse Events (TEAE) were reported for both Adverse Event (AE) and Serious Adverse Events (SAE). TEAE's are events that began or worsen in severity after the first administration of treatment.	18.4% 21/114 • Number of events 25 • Day -30 (Pre-operative) to Day 60 (+/- 3 days) Treatment-Emergent Adverse Events (TEAE) were reported for both Adverse Event (AE) and Serious Adverse Events (SAE). TEAE's are events that began or worsen in severity after the first administration of treatment.
Vascular disorders Hypertension	4.5% 5/110 • Number of events 5 • Day -30 (Pre-operative) to Day 60 (+/- 3 days) Treatment-Emergent Adverse Events (TEAE) were reported for both Adverse Event (AE) and Serious Adverse Events (SAE). TEAE's are events that began or worsen in severity after the first administration of treatment.	5.3% 6/114 • Number of events 6 • Day -30 (Pre-operative) to Day 60 (+/- 3 days) Treatment-Emergent Adverse Events (TEAE) were reported for both Adverse Event (AE) and Serious Adverse Events (SAE). TEAE's are events that began or worsen in severity after the first administration of treatment.

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee
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