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

NCT02891070 | Completed Phase 3 Results DMC

• 2 other identifiers: 3599-0012015-005535-40
• Study Type: interventional
• Target: 224
• Locations: 4 countries
• Sites: 25

Brief Summary

The objective of this study is to evaluate the safety and efficacy of FS VH S/D 500 s-apr for use as an adjunct to sutured dural repair in cranial surgery.

Conditions

Cerebrospinal Fluid Leak

Keywords

Cranial Surgery; Cerebrospinal Fluid Leak; Tisseel

Outcome Measures

Primary Outcomes (1)

• 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 (5)

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

  Day 0 (Intra-operative)

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

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

• Duration in Surgery (Minutes)

  Day 0 (intra-operatively)

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

  Day 0 (Intra-operatively)

• Length of Stay in Hospital (Days).

  Day 0 to Day 60 (Study Completion)

Study Arms (2)

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

Interventions

FS VH S/D 500 s-apr DRUG

Also known as: Tisseel

FS VH S/D 500 s-apr

DuraSeal Dural Sealant DEVICE

DuraSeal Dural Sealant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Baxter Healthcare Corporation: lead

Study Sites (25)

Southern Illinois University School of Medicine

Springfield, Illinois, 62702, United States

Location

Baystate Medical Center

Springfield, Massachusetts, 01199, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

The Ohio State University

Columbus, Ohio, 43201, United States

Location

Temple University School of Medicine

Philadelphia, Pennsylvania, 19140, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Houston Methodist Neurological Institute

Houston, Texas, 77030, United States

Location

University of Virginia School of Medicine

Charlottesville, Virginia, 22903, United States

Location

University Hospital Brno

Brno, 62500, Czechia

Location

St. Anne's University Hospital Brno

Brno, 65691, Czechia

Location

University Hospital Hradec Kralove

Hradec Králové, 50005, Czechia

Location

University Hospital Ostrava

Ostrava, 70852, Czechia

Location

Hospital Na Homolce

Prague, 15030, Czechia

Location

University Hospital Motol

Praha 5 - Motol, 15006, Czechia

Location

University Hospital Leipzig

Leipzig, 04103, Germany

Location

Hospital Bogenhausen Municipal Hospital

Munich, 81925, Germany

Location

University Hospital Rostock

Rostock, 18057, Germany

Location

University Hospital Germans Trias I Pujol

Badalona, 08916, Spain

Location

Hospital Clinic I Provincial de Barcelona

Barcelona, 08036, Spain

Location

University Hospital Foundation Jimenez Diaz

Madrid, 28040, Spain

Location

University Hospital 12 de Octubre

Madrid, 28041, Spain

Location

University Hospital Son Espases

Palma de Mallorca, 07010, Spain

Location

University General Hospital of Valencia

Valencia, 46014, Spain

Location

MeSH Terms

Conditions

Cerebrospinal Fluid Leak

Interventions

Low Density Lipoprotein Receptor-Related Protein-1; Fibrin Tissue Adhesive

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Wounds and Injuries

Intervention Hierarchy (Ancestors)

LDL-Receptor Related Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, LDL; Receptors, Lipoprotein; Receptors, Cell Surface; Membrane Proteins; Fibrin; Blood Proteins

Results Point of Contact

• Title: Baxter Clinical Trials Disclosure Call Center
• Organization: Baxter Healtcare

Global_CORP_ClinicalTrialsDisclosure@baxter.com

(224) 948-7359

Study Officials

• Qing Li, MD, PhD

  Baxter Healthcare

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2016
• First Posted: September 7, 2016
• Study Start: October 11, 2016
• Primary Completion: August 22, 2018
• Study Completion: August 22, 2018
• Last Updated: September 10, 2019
• Results First Posted: September 10, 2019

Record last verified: 2019-08

Locations

US (10); ES (6); DE (3); CZ (6)