Trial Outcomes & Findings for Safety and Effectiveness of the Adherus Dural Sealant System When Used as a Dural Sealant in Cranial Procedures (NCT NCT01158378)
NCT ID: NCT01158378
Last Updated: 2014-04-08
Results Overview
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.
COMPLETED
PHASE3
250 participants
120 days
2014-04-08
Participant Flow
The first subject was treated on September 3, 2010 and the last subject visit occurred on January 17, 2013.
Randomized study, no washout or run-in period.
Participant milestones
| Measure |
Adherus Dural Sealant
Adherus Dural Sealant: In situ polymerizing sealant
|
DuraSeal Dural Sealant System
DuraSeal Dural Sealant System: In situ polymerizing sealant
|
|---|---|---|
|
Overall Study
STARTED
|
124
|
126
|
|
Overall Study
COMPLETED
|
114
|
117
|
|
Overall Study
NOT COMPLETED
|
10
|
9
|
Reasons for withdrawal
| Measure |
Adherus Dural Sealant
Adherus Dural Sealant: In situ polymerizing sealant
|
DuraSeal Dural Sealant System
DuraSeal Dural Sealant System: In situ polymerizing sealant
|
|---|---|---|
|
Overall Study
Death
|
4
|
5
|
|
Overall Study
Lost to Follow-up
|
2
|
4
|
|
Overall Study
Withdrawal by Subject
|
4
|
0
|
Baseline Characteristics
Safety and Effectiveness of the Adherus Dural Sealant System When Used as a Dural Sealant in Cranial Procedures
Baseline characteristics by cohort
| Measure |
Adherus Dural Sealant
n=120 Participants
Adherus Dural Sealant: In situ polymerizing sealant
|
DuraSeal Dural Sealant System
n=122 Participants
DuraSeal Dural Sealant System: In situ polymerizing sealant
|
Total
n=242 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
|
51.1 years
STANDARD_DEVIATION 14.0 • n=5 Participants
|
49.6 years
STANDARD_DEVIATION 15.1 • n=7 Participants
|
50.4 years
STANDARD_DEVIATION 15.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
41 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
79 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
79 Participants
n=5 Participants
|
84 Participants
n=7 Participants
|
163 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
120 participants
n=5 Participants
|
122 participants
n=7 Participants
|
242 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 120 daysPopulation: All subjects who received treatment with evaluable 120-day follow-up data.
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.
Outcome measures
| Measure |
Adherus Dural Sealant System
n=114 Participants
Adherus Dural Sealant: In situ polymerizing sealant
|
DuraSeal Dural Sealant System
n=117 Participants
DuraSeal Dural Sealant System: In situ polymerizing sealant
|
|---|---|---|
|
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
Interval 84.5 to 95.7
|
90.6 percentage of subjects
Interval 83.8 to 95.2
|
SECONDARY outcome
Timeframe: 120 daysPopulation: Includes all subjects with available data that through 120 days 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.
Outcome measures
| Measure |
Adherus Dural Sealant System
n=114 Participants
Adherus Dural Sealant: In situ polymerizing sealant
|
DuraSeal Dural Sealant System
n=117 Participants
DuraSeal Dural Sealant System: In situ polymerizing sealant
|
|---|---|---|
|
Proportion of Subjects Free of Device-related Surgical Wound Infections or Meningitis During 120-day Follow-up.
|
100 percentage of subjects
|
98.3 percentage of subjects
|
POST_HOC outcome
Timeframe: 14 daysPopulation: All subjects who received treatment with evaluable 14-day follow-up data.
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.
Outcome measures
| Measure |
Adherus Dural Sealant System
n=117 Participants
Adherus Dural Sealant: In situ polymerizing sealant
|
DuraSeal Dural Sealant System
n=120 Participants
DuraSeal Dural Sealant System: In situ polymerizing sealant
|
|---|---|---|
|
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
Interval 95.3 to 100.0
|
95.0 percentage of subjects
Interval 89.4 to 98.1
|
POST_HOC outcome
Timeframe: 45 daysPopulation: All subjects who received treatment with evaluable 45-day follow-up data.
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.
Outcome measures
| Measure |
Adherus Dural Sealant System
n=119 Participants
Adherus Dural Sealant: In situ polymerizing sealant
|
DuraSeal Dural Sealant System
n=123 Participants
DuraSeal Dural Sealant System: In situ polymerizing sealant
|
|---|---|---|
|
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
Interval 91.6 to 99.1
|
91.9 percentage of subjects
Interval 85.6 to 96.0
|
Adverse Events
Adherus Dural Sealant System
DuraSeal Dural Sealant System
Serious adverse events
| Measure |
Adherus Dural Sealant System
n=124 participants at risk
Adherus Dural Sealant: In situ polymerizing sealant
|
DuraSeal Dural Sealant System
n=126 participants at risk
DuraSeal Dural Sealant System: In situ polymerizing sealant
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.81%
1/124 • Number of events 1 • 120 days
|
0.00%
0/126 • 120 days
|
|
Cardiac disorders
Atrial Fibrillation
|
0.00%
0/124 • 120 days
|
0.79%
1/126 • Number of events 1 • 120 days
|
|
Ear and labyrinth disorders
Deafness Unilateral
|
0.81%
1/124 • Number of events 1 • 120 days
|
0.00%
0/126 • 120 days
|
|
Ear and labyrinth disorders
Hypoacusis
|
0.00%
0/124 • 120 days
|
0.79%
1/126 • Number of events 1 • 120 days
|
|
Gastrointestinal disorders
Diverticular Perforation
|
0.00%
0/124 • 120 days
|
0.79%
1/126 • Number of events 1 • 120 days
|
|
Gastrointestinal disorders
Dysphagia
|
0.81%
1/124 • Number of events 1 • 120 days
|
0.00%
0/126 • 120 days
|
|
Gastrointestinal disorders
Faecaloma
|
0.00%
0/124 • 120 days
|
0.79%
1/126 • Number of events 1 • 120 days
|
|
Gastrointestinal disorders
Hiatus Hernia
|
0.00%
0/124 • 120 days
|
0.79%
1/126 • Number of events 1 • 120 days
|
|
Gastrointestinal disorders
Intestinal Obstruction
|
0.00%
0/124 • 120 days
|
0.79%
1/126 • Number of events 1 • 120 days
|
|
General disorders
Adverse Drug Reaction
|
0.00%
0/124 • 120 days
|
1.6%
2/126 • Number of events 2 • 120 days
|
|
General disorders
Disease Progression
|
1.6%
2/124 • Number of events 2 • 120 days
|
2.4%
3/126 • Number of events 3 • 120 days
|
|
Infections and infestations
Bronchitis
|
0.00%
0/124 • 120 days
|
0.79%
1/126 • Number of events 1 • 120 days
|
|
Infections and infestations
Diverticulitis
|
0.00%
0/124 • 120 days
|
0.79%
1/126 • Number of events 1 • 120 days
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/124 • 120 days
|
0.79%
1/126 • Number of events 1 • 120 days
|
|
Infections and infestations
Incision Site Infection
|
0.00%
0/124 • 120 days
|
1.6%
2/126 • Number of events 2 • 120 days
|
|
Infections and infestations
Infection
|
0.00%
0/124 • 120 days
|
0.79%
1/126 • Number of events 1 • 120 days
|
|
Infections and infestations
Pneumonia Viral
|
0.81%
1/124 • Number of events 1 • 120 days
|
0.00%
0/126 • 120 days
|
|
Infections and infestations
Sepsis
|
0.00%
0/124 • 120 days
|
0.79%
1/126 • Number of events 1 • 120 days
|
|
Infections and infestations
Wound Infection
|
0.81%
1/124 • Number of events 1 • 120 days
|
0.00%
0/126 • 120 days
|
|
Injury, poisoning and procedural complications
Brain Contusion
|
0.81%
1/124 • Number of events 1 • 120 days
|
0.00%
0/126 • 120 days
|
|
Injury, poisoning and procedural complications
Brain Herniation
|
0.00%
0/124 • 120 days
|
0.79%
1/126 • Number of events 1 • 120 days
|
|
Injury, poisoning and procedural complications
Extradural Haematoma
|
0.81%
1/124 • Number of events 1 • 120 days
|
0.00%
0/126 • 120 days
|
|
Injury, poisoning and procedural complications
Pseudomeningocele
|
2.4%
3/124 • Number of events 3 • 120 days
|
0.79%
1/126 • Number of events 1 • 120 days
|
|
Injury, poisoning and procedural complications
Radiation Injury
|
0.00%
0/124 • 120 days
|
0.79%
1/126 • Number of events 1 • 120 days
|
|
Injury, poisoning and procedural complications
Seroma
|
1.6%
2/124 • Number of events 2 • 120 days
|
0.00%
0/126 • 120 days
|
|
Metabolism and nutrition disorders
Dehydration
|
0.81%
1/124 • Number of events 1 • 120 days
|
0.00%
0/126 • 120 days
|
|
Metabolism and nutrition disorders
Electrolyte Imbalance
|
0.81%
1/124 • Number of events 1 • 120 days
|
0.00%
0/126 • 120 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer Metastatic
|
0.81%
1/124 • Number of events 1 • 120 days
|
0.00%
0/126 • 120 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer Recurrent
|
0.00%
0/124 • 120 days
|
0.79%
1/126 • Number of events 1 • 120 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon Cancer
|
0.00%
0/124 • 120 days
|
0.79%
1/126 • Number of events 1 • 120 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung Cancer Metastatic
|
0.81%
1/124 • Number of events 1 • 120 days
|
0.00%
0/126 • 120 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic Neoplasm
|
0.00%
0/124 • 120 days
|
0.79%
1/126 • Number of events 1 • 120 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Sarcoma
|
0.00%
0/124 • 120 days
|
0.79%
1/126 • Number of events 1 • 120 days
|
|
Nervous system disorders
Basal Ganglia Infarction
|
0.81%
1/124 • Number of events 1 • 120 days
|
0.00%
0/126 • 120 days
|
|
Nervous system disorders
Cerebellar Haemorrhage
|
0.81%
1/124 • Number of events 1 • 120 days
|
0.00%
0/126 • 120 days
|
|
Nervous system disorders
Cerebral Haemorrhage
|
0.00%
0/124 • 120 days
|
1.6%
2/126 • Number of events 2 • 120 days
|
|
Nervous system disorders
Cerebrospinal Fluid Rhinorrhoea
|
0.00%
0/124 • 120 days
|
0.79%
1/126 • Number of events 1 • 120 days
|
|
Nervous system disorders
Cerebrovascular Accident
|
0.81%
1/124 • Number of events 1 • 120 days
|
2.4%
3/126 • Number of events 3 • 120 days
|
|
Nervous system disorders
Convulsion
|
2.4%
3/124 • Number of events 3 • 120 days
|
0.00%
0/126 • 120 days
|
|
Nervous system disorders
Dyspraxia
|
0.81%
1/124 • Number of events 1 • 120 days
|
0.00%
0/126 • 120 days
|
|
Nervous system disorders
Embolic Stroke
|
1.6%
2/124 • Number of events 2 • 120 days
|
0.79%
1/126 • Number of events 1 • 120 days
|
|
Nervous system disorders
Gran Mal Convulsion
|
0.81%
1/124 • Number of events 1 • 120 days
|
0.00%
0/126 • 120 days
|
|
Nervous system disorders
Headache
|
0.81%
1/124 • Number of events 1 • 120 days
|
0.00%
0/126 • 120 days
|
|
Nervous system disorders
Hemiparesis
|
0.81%
1/124 • Number of events 1 • 120 days
|
0.00%
0/126 • 120 days
|
|
Nervous system disorders
Hydrocephalus
|
0.00%
0/124 • 120 days
|
0.79%
1/126 • Number of events 1 • 120 days
|
|
Nervous system disorders
Intracranial Hypotension
|
0.00%
0/124 • 120 days
|
0.79%
1/126 • Number of events 1 • 120 days
|
|
Nervous system disorders
Intracranial Venous Sinus Thrombosis
|
0.00%
0/124 • 120 days
|
0.79%
1/126 • Number of events 1 • 120 days
|
|
Nervous system disorders
Ischaemic Cerebral Infarction
|
0.00%
0/124 • 120 days
|
0.79%
1/126 • Number of events 1 • 120 days
|
|
Nervous system disorders
Memory Impairment
|
0.81%
1/124 • Number of events 1 • 120 days
|
0.00%
0/126 • 120 days
|
|
Nervous system disorders
Metabolic Encephalopathy
|
0.00%
0/124 • 120 days
|
0.79%
1/126 • Number of events 1 • 120 days
|
|
Nervous system disorders
Thalamic Infarction
|
0.81%
1/124 • Number of events 1 • 120 days
|
0.00%
0/126 • 120 days
|
|
Nervous system disorders
Toxic Encephalopathy
|
0.00%
0/124 • 120 days
|
0.79%
1/126 • Number of events 1 • 120 days
|
|
Nervous system disorders
VIIth Nerve Paralysis
|
0.81%
1/124 • Number of events 1 • 120 days
|
0.00%
0/126 • 120 days
|
|
Nervous system disorders
Vocal Cord Paralysis
|
0.81%
1/124 • Number of events 1 • 120 days
|
0.00%
0/126 • 120 days
|
|
Psychiatric disorders
Anxiety
|
0.81%
1/124 • Number of events 1 • 120 days
|
0.00%
0/126 • 120 days
|
|
Psychiatric disorders
Panic Disorder
|
0.00%
0/124 • 120 days
|
0.79%
1/126 • Number of events 1 • 120 days
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.81%
1/124 • Number of events 1 • 120 days
|
0.00%
0/126 • 120 days
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
0.81%
1/124 • Number of events 1 • 120 days
|
0.00%
0/126 • 120 days
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia Aspiration
|
0.81%
1/124 • Number of events 1 • 120 days
|
0.00%
0/126 • 120 days
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
1.6%
2/124 • Number of events 2 • 120 days
|
0.00%
0/126 • 120 days
|
|
Skin and subcutaneous tissue disorders
Drug Rash With Eosinophilia and Systemic Symptoms
|
0.81%
1/124 • Number of events 1 • 120 days
|
0.00%
0/126 • 120 days
|
|
Vascular disorders
Hypertension
|
0.00%
0/124 • 120 days
|
0.79%
1/126 • Number of events 1 • 120 days
|
Other adverse events
| Measure |
Adherus Dural Sealant System
n=124 participants at risk
Adherus Dural Sealant: In situ polymerizing sealant
|
DuraSeal Dural Sealant System
n=126 participants at risk
DuraSeal Dural Sealant System: In situ polymerizing sealant
|
|---|---|---|
|
Eye disorders
Vision Blurred
|
5.6%
7/124 • Number of events 7 • 120 days
|
5.6%
7/126 • Number of events 7 • 120 days
|
|
Nervous system disorders
Dizziness
|
5.6%
7/124 • Number of events 7 • 120 days
|
3.2%
4/126 • Number of events 4 • 120 days
|
|
Nervous system disorders
Headache
|
10.5%
13/124 • Number of events 14 • 120 days
|
12.7%
16/126 • Number of events 17 • 120 days
|
|
Nervous system disorders
Hypoaesthesia
|
3.2%
4/124 • Number of events 4 • 120 days
|
7.1%
9/126 • Number of events 9 • 120 days
|
Additional Information
Michael Carnahan, PhD
HyperBranch Medical Technology, Inc
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place