Bioseal Dural Sealing Study BIOS-14-001

A Prospective, Randomized, Controlled, Single Blinded, Study to Evaluate the Safety and Effectiveness of Bioseal as an Adjunct to Sutured Dural Repair

A Prospective, Randomized, Controlled, Single Blinded, Study to Evaluate the Safety and Effectiveness of Bioseal as an Adjunct to Sutured Dural Repair

Study Overview

• Status: Completed
• Conditions: Malignant Tumors; Vascular Malformation; Benign Tumors
• Intervention / Treatment: Biological: Bioseal

Detailed Description

This is a randomized, single blinded, multi-center controlled study evaluating the effectiveness of Bioseal as an adjunct to sutured dural closure compared to control to obtain an intra-operative watertight dural closure.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100053
      • Xuanwu Hospital Capital Medical University
  • Fujian
    • Fuzhou, Fujian, China, 350005
      • The First Affiliated Hospital Of Fujian Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510280
      • Zhujiang Hospital of Southern Medical University
  • Guizhou
    • Guiyang, Guizhou, China, 550004
      • The Affiliated Hospital of Guizhou Medical University
  • Henan
    • Zhengzhou, Henan, China
      • The First Affiliated Hospital of Zhengzhou University
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital, Tongji Medical College of HUST
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • The First Affiliated Hospital of Soochow University
    • Xuzhou, Jiangsu, China, 221000
      • The Affiliated Hospital Of XuZhou Medical University
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Huashan hospital, Shanghai Medical College, Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Preoperative

  1. Patient undergoing elective craniotomy/craniectomy for pathological processes (such as benign and malignant tumors, vascular malformation) in the posterior fossa or in the supratentorial region.
  2. Age ≥ 18 years.
  3. Patients who are able and willing to comply with the procedures required by the protocol.
  4. Signed and dated written informed consent from the subject or from his/her legal representative prior to any study-specific procedures.

• Intraoperative

  1. Patient undergoing elective craniotomy/craniectomy for pathological processes (such as benign and malignant tumors, vascular malformation) in the posterior fossa or in the supratentorial region and who are demonstrated to have persistent CSF leakage following suture closure of the dural incision. CSF leakage will be evaluated during a period of Valsalva of 10-20 cm of H20 for 5-10 seconds. If a spontaneous leak is apparent immediately after dural closure, no Valsalva will be performed.
  2. Surgical wound classification Class I. Penetration of mastoid air cells during partial mastoidectomy is permitted.
  3. The cuff of native dura along the craniotomy edge is ≥10 mm wide, to facilitate suturing and to allow for sufficient surface area for adherence of the investigational product.

Exclusion Criteria:

• Preoperative

  1. Subjects with a dura lesion from a recent surgery that still has the potential for CSF leakage.
  2. The previous craniotomy/ craniectomy within 6 months or radiation therapy within 2 years before this surgery.
  3. Chemotherapy or radiation therapy scheduled within 7 days following surgery.
  4. Subjects with severely altered renal (serum creatinine >2 mg/dL) and/or hepatic function [ALT, AST > 5 x upper limit of norm (ULN)].
  5. Severe Anemia (Hemoglobin <60 g/L) or Hypoproteinemia (Total protein <60 g/L or 6g% ) .
  6. Non-compliant or insufficient treatment of diabetes mellitus [glycosylated hemoglobin (HbA1c) > 7.5%].
  7. Conditions compromising the immune system; existence of autoimmune disease.
  8. Evidence of a potential infection: fever >38℃, WBC <3500/uL or >13000/uL, positive urine culture, positive blood culture, positive chest X-ray, evidence of infection along the planned surgical path.
  9. Known hypersensitivity to the porcine fibrin sealant product.
  10. Female subjects of childbearing potential with a positive urine or serum pregnancy test within 7 days prior to surgery.
  11. Female subjects who are breastfeeding or intend to become pregnant during the clinical study period.
  12. Participation in another clinical trial with exposure to another investigational drug or device within 30 days prior to enrolment.

• Intraoperative

  1. Native dura cuff during craniotomy/craniectomy that cannot be completely repaired.
  2. Use of implants made of synthetic materials coming into direct contact with dura (e.g., PTFE patches, shunts, ventricular and subdural drains).
  3. Occlusive hydrocephalus caused by posterior fossa pathology or partial blockage of CSF pathways during surgical procedure.
  4. Existing CSF drains on the surgical path.
  5. Use of other fibrin sealants for hemostasis.
  6. Placement of Gliadel Wafers or similar products.
  7. Persistently increased brain surface tension that may lead to an incomplete repair requiring.
  8. Intersecting durotomy scars in the surgical path from a previous operation that cannot be completely removed by the planned dura resection.
  9. Two or more separate dura defects during surgery.
  10. Others in addition to above exclusion criteria, the subject, in the opinion of the investigator, would not be suitable for participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: suture (control); Subjects randomized to control will receive additional dural sutures as deemed necessary by the surgeon. CSF leakage will be re-evaluated with the Valsalva maneuver to 10-20 cm H2O for 5 to 10 seconds. Closure of the remaining layers of the surgical site will be performed according to the surgeon's standard of practice.
Experimental: Bioseal; Subjects randomized to receive Bioseal, a thin layer will be applied to the entire length of the suture line and the adjacent area to approximately 5mm away, including all suture holes. Up to two layers of Bioseal may be used for each application. While Bioseal achieves complete coagulation, CSF leakage will be re-evaluated with the Valsalva maneuver to 10-20 cm H2O for 5 to 10 seconds. Up to two applications (one application includes applying up to two layers of Bioseal product followed by the CSF leakage re-evaluation with Valsalva maneuver) per subject are allowed. Closure of the remaining layers of the surgical site will be performed according to the surgeon's standard of practice.	Biological: Bioseal; Upon completion of the sutured dural repair, the closure will be evaluated for intra-operative CSF leakage with a baseline Valsalva maneuver to 10-20 cm H2O for 5-10 seconds. Subjects who have a CSF leak will be enrolled into the study. If randomized to receive Bioseal, a thin layer will be applied to the entire length of the suture line and the adjacent area to approximately 5mm away, including all suture holes. Up to two layers of Bioseal may be used for each application. While Bioseal achieves complete coagulation, CSF leakage will be re-evaluated with the Valsalva maneuver to 10-20 cm H2O for 5 to 10 seconds.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of success (watertight closure) CSF leakage	no CSF leakage from dural repair intra-operatively	5 to 10 seconds after final Valsalva maneuver

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of CSF leakage	Incidence of CSF leakage post-surgery to discharge	Up to Discharge, an average of 3-5days in general
Incidence of CSF leakage	Incidence of CSF leakage 30 (±7) days post operatively	Up to 30(+/-7)Days
Incidence of adverse events	Incidence of adverse events	Up to 30(±7)Days
Incidence of surgical site infections (SSI)	Incidence of surgical site infections (SSI) according to Surgical Site Infection Infection Prevention and Control Guideline (MOH) criteria	Up to 30(± 7) days

Collaborators and Investigators

• Sponsor: Guangzhou Bioseal Biotechnology Co., Ltd.
• Investigators: Principal Investigator: Ying Mao, MD, PhD, Hua Shan Hospital, Shanghai Medical College, Fudan University

Publications and helpful links

General Publications

• Du S, Zhao J, Qiao G, Wu S, Han Y. Cost-Effectiveness Analysis of the Application of a Porcine-Derived Fibrin Sealant for the Treatment of Cerebrospinal Fluid Leak in China. Clin Ther. 2022 Apr;44(4):575-584. doi: 10.1016/j.clinthera.2022.02.010. Epub 2022 Apr 19.

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2017
• Primary Completion (Actual): September 20, 2019
• Study Completion (Actual): September 20, 2019

Study Registration Dates

• First Submitted: March 22, 2017
• First Submitted That Met QC Criteria: April 11, 2017
• First Posted (Actual): April 12, 2017

Study Record Updates

• Last Update Posted (Actual): November 18, 2019
• Last Update Submitted That Met QC Criteria: November 15, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Bioseal as an Adjunct to Sutured Dural Repair; elective posterior fossa; supratentorial procedure
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Vascular Malformations
• Other Study ID Numbers: BIOS-14-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No