Efficacy and Safety of FS VH S/D 500 S-apr (Tisseel) as a... | NCT02891070

NCT02891070

ID	Type	Description	Link
2015-005535-40	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
FS VH S/D 500 s-apr	Experimental	FS VH S/D 500 s-apr (Tisseel), single use treatment, intraoperative	Drug: FS VH S/D 500 s-apr
DuraSeal Dural Sealant	Active Comparator	DuraSeal Dural Sealant, single use treatment, intraoperative	Device: DuraSeal Dural Sealant

Name	Type	Description	Arm Group Labels	Other Names
FS VH S/D 500 s-apr	Drug		FS VH S/D 500 s-apr	Tisseel
DuraSeal Dural Sealant

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With No CSF Leak During and After Surgery	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.	Day 0 (Intra-operative) to Day 30 (+/-3 days) post-operative

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With no Intra-operative CSF Leaks Following Final Valsalva Maneuver	Assessment of whether the suture line was not watertight causing CSF leaks after up to two product/control applications and Valsalva maneuvers.	Day 0 (Intra-operative)
Number of Participants With CSF Leaks Within 30 (+3) Days Post-operatively

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Patients undergoing craniotomy/craniectomy for pathological processes in the PF or ST region
Patients must be willing and able to participate in the study and provide written IC before any protocol specific assessment is performed
Patients must be willing to receive peri-operative antibiotic prophylaxis
Female patients of childbearing potential must present with a negative serum pregnancy test, and must agree to employ adequate birth control measures [restricted to abstinence, barrier contraceptives, intrauterine contraceptive devices or licensed hormonal products] for the duration of their participation in the study
Patients are willing and able to comply with the requirements of the protocol

Exclusion Criteria:

Patients with a dural lesion from a recent surgery that still has the potential for CSF leakage
Patients who had undergone chemotherapy treatment, excluding hormonal therapy, within 3 weeks prior to the planned procedure, or with chemotherapy scheduled within 7 days following surgery
Patients with radiation therapy to the surgical site or standard fractionated radiation therapy scheduled within 7 days following surgery
Patients with a previous craniotomy/craniectomy within 6 months prior to the study surgery
Use of corticosteroids on a chronic basis (defined as daily use of corticosteroids for ≥8 weeks) for purposes other than decreasing the symptoms of systemic chemotherapy (unless if those steroids were discontinued 4 weeks prior to the planned surgery)
Patients with a known hypersensitivity to the components of the IP or control (human fibrinogen, synthetic aprotinin, human albumin, human FXIII, tri sodium citrate, histidine, niacinamide, polysorbate 80, human thrombin, polyethylene glycol [PEG], trilysine amine)
Patients with a known hypersensitivity to US Federal Drug & Cosmetic Blue #1 dye
Evidence of an infection indicated by any one of the following: clinical examination supporting the diagnosis of infection, fever (temperature >100.7°F or 38.2°C), positive urine culture, positive blood culture, positive chest X ray consistent with pulmonary infection, or infection along the planned surgical path. A white blood cell (WBC) count of <20000 cells/µL is permitted if the patient is being treated with steroids in the absence of all other infection parameters
Female patients of childbearing potential with a positive pregnancy test or intent to become pregnant during the clinical study period
Female patients who are nursing
Patients with exposure to another investigational drug or device clinical trial within 30 days prior to enrolment or anticipated in the 60-day Follow-up period
Patients with severely altered renal function as confirmed by local laboratory reference ranges for serum creatinine and/or hepatic function (alanine aminotransferase [ALT], aspartate aminotransferase >3 × upper limit of normal [ULN])
Patients who currently have or have had a compromised immune system (such as Acquired Immune Deficiency Syndrome [AIDS]) or autoimmune disease, or were on chronic immunosuppressant agents
Patients with uncontrolled diabetes as evidenced by the institution's standard of care (glycated haemoglobin [HbA1c] >7%, blood glucose, etc.)
Patients with traumatic injuries to the head
Patients with dural injury during craniotomy/craniectomy that cannot be eliminated by widening the craniotomy/craniectomy to recreate the native dural cuff
Patients requiring surgical approaches that would not allow sutured dural closure such as trans-sphenoidal or translabyrinthine/-petrosal/-mastoid. Superficial penetration of mastoid air cells is allowed
Patients with hydrocephalus, except occlusive hydrocephalus caused by PF pathology or incompletely open cerebrospinal fluid pathways, to be treated during surgical procedure
Existing CSF (ventricular, etc.) drains, Cushing/Dandy cannulation, or Burr holes which damage the dura
Patients with confined bony structures where nerves are present and neural compression may result due to swelling

Contacts/Locations Module

Name	Affiliation	Role
Qing Li, MD, PhD	Baxter Healthcare	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Southern Illinois University School of Medicine		Springfield	Illinois	62702	United States
Baystate Medical Center

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 6, 2017	Aug 21, 2019

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Full analysis set (FAS): The FAS consisted of all patients who were randomized and treated with at least 1 dose of IP/control. Patients were analyzed as randomized.

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	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.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00051.8± 14.24 BG00151.3± 14.85 BG00251.5± 14.53

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00066 BG00165 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With No CSF Leak During and After Surgery

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.

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.

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG00089 OG00195

Title

Denominators

Categories

Title	Measurements
	OG00076 OG00187

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Regression, Logistic				Mean Difference (Net)	-9.29			2-Sided	95	-21.11	2.54			Difference in Average Predicted Proportion (Tisseel - Duraseal)		Non-Inferiority	To demonstrate non-inferiority (NI) of Tisseel to DuraSeal for the primary endpoint, the lower limit of the 95% CI (based on normal approximation) for the difference in average predicted proportions had to be greater than -10%.

Secondary

Number of Participants With no Intra-operative CSF Leaks Following Final Valsalva Maneuver

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

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.

Posted

Count of Participants

Participants

Day 0 (Intra-operative)

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts

Secondary

Number of Participants With CSF Leaks Within 30 (+3) Days Post-operatively

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.

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.

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Duration in Surgery (Minutes)

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.

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.

Posted

Mean

Standard Deviation

Minutes

Day 0 (intra-operatively)

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts

Secondary

Time From Dural Closure (Application of IP) Until End of Surgery

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

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.

Posted

Mean

Standard Deviation

Minutes

Day 0 (Intra-operatively)

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants

Secondary

Length of Stay in Hospital (Days).

Days in hospital calculation is Day 0 - Discharge.

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.

Posted

Mean

Standard Deviation

Days

Day 0 to Day 60 (Study Completion)

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants

Post-Hoc

Number of Surgical Site Infections (SSI)

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.

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

Posted

Number

SSI

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

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	3	110	22	110	46	110
EG001	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.	0	114	17	114	46	114

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cardiac Arrest	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0001 events1 affected110 at risk EG0010 events0 affected114 at risk
Adrenal Insufficiency	Endocrine disorders	MedDRA (18.0)	Systematic Assessment	EG0001 events1 affected110 at risk EG0010 events0 affected114 at risk
Abdominal Discomfort	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected110 at risk EG0011 events1 affected114 at risk
Pyrexia	General disorders	MedDRA (18.0)	Systematic Assessment	EG0001 events1 affected110 at risk EG0010 events0 affected114 at risk
Brain Abscess	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected110 at risk EG0012 events2 affected114 at risk
Brain Empyema	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected110 at risk EG0011 events1 affected114 at risk
Epidural Empyema	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected110 at risk EG0011 events1 affected114 at risk
Hepatitis E	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 events1 affected110 at risk EG0010 events0 affected114 at risk
Osteomyelitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected110 at risk EG0012 events2 affected114 at risk
Pneumonia	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 events1 affected110 at risk EG0011 events1 affected114 at risk
Soft Tissue Infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected110 at risk EG0011 events1 affected114 at risk
Wound Infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected110 at risk EG0012 events2 affected114 at risk
Brain Contusion	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0001 events1 affected110 at risk EG0010 events0 affected114 at risk
Extradural Haematoma	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected110 at risk EG0011 events1 affected114 at risk
Femur Fracture	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected110 at risk EG0011 events1 affected114 at risk
Pneumocephalus	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0002 events1 affected110 at risk EG0010 events0 affected114 at risk
Post Procedural Haemorrhage	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected110 at risk EG0011 events1 affected114 at risk
Pseudomeningocele	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected110 at risk EG0011 events1 affected114 at risk
Wound Dehiscence	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected110 at risk EG0012 events2 affected114 at risk
Wound Haematoma	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0001 events1 affected110 at risk EG0010 events0 affected114 at risk
Brain Oedema	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 events1 affected110 at risk EG0012 events2 affected114 at risk
Cerebrospinal Fluid Leakage	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0007 events7 affected110 at risk EG0011 events1 affected114 at risk
Dizziness	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 events1 affected110 at risk EG0010 events0 affected114 at risk
Hydrocephalus	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0003 events3 affected110 at risk EG0011 events1 affected114 at risk
Idiopathic Intracranial Hypertension	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected110 at risk EG0011 events1 affected114 at risk
Sensorimotor Disorder	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected110 at risk EG0011 events1 affected114 at risk
Superior Sagittal Sinus Thrombosis	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected110 at risk EG0011 events1 affected114 at risk
Thalamic Infarction	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 events1 affected110 at risk EG0010 events0 affected114 at risk
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 events1 affected110 at risk EG0010 events0 affected114 at risk
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 events1 affected110 at risk EG0010 events0 affected114 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0002 events2 affected110 at risk EG0010 events0 affected114 at risk
Pulmonary Embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0002 events2 affected110 at risk EG0010 events0 affected114 at risk
Respiratory Distress	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 events1 affected110 at risk EG0010 events0 affected114 at risk
Respiratory Failure	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0002 events2 affected110 at risk EG0010 events0 affected114 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected110 at risk EG0011 events1 affected114 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Constipation	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0009 events8 affected110 at risk EG0015 events5 affected114 at risk
Nausea	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG00012 events10 affected110 at risk EG00116 events14 affected114 at risk
Vomiting	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG00015 events10 affected110 at risk EG00117 events14 affected114 at risk
Pain	General disorders	MedDRA (18.0)	Systematic Assessment	EG00015 events15 affected110 at risk EG00116 events15 affected114 at risk
Pyrexia	General disorders	MedDRA (18.0)	Systematic Assessment	EG0006 events3 affected110 at risk EG0017 events7 affected114 at risk
Dizziness	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0008 events6 affected110 at risk EG0014 events3 affected114 at risk
Headache	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG00025 events20 affected110 at risk EG00125 events21 affected114 at risk
Hypertension	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG0005 events5 affected110 at risk EG0016 events6 affected114 at risk

ID	Term
D065634	Cerebrospinal Fluid Leak

Ancestor Terms

ID	Term
D009461	Neurologic Manifestations
D009422	Nervous System Diseases
D006259	Craniocerebral Trauma
D020196	Trauma, Nervous System
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms
D014947	Wounds and Injuries

ID	Term
D026503	Low Density Lipoprotein Receptor-Related Protein-1
D015718	Fibrin Tissue Adhesive

Ancestor Terms

ID	Term
D026502	LDL-Receptor Related Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D011973	Receptors, LDL
D018110	Receptors, Lipoprotein
D011956	Receptors, Cell Surface
D008565	Membrane Proteins
D005337	Fibrin
D001798	Blood Proteins