Bioseal Dural Sealing Study BIOS-14-001

Phase 3

Completed

• Conditions: Malignant Tumors; Benign Tumors; Vascular Malformation
• Interventions: Biological: Bioseal

• Registration Number: NCT03110783
• Lead Sponsor: Guangzhou Bioseal Biotechnology Co., Ltd.

Brief Summary

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

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 Timeline

• Study First Submitted: 2017-03-22
• Study First Submitted QC: 2017-04-11
• Study First Posted: 2017-04-12
• Study Start: 2017-09-14
• Primary Completion: 2019-09-20
• Study Completion: 2019-09-20
• Status Verified: 2019-11
• Last Update Submitted: 2019-11-15
• Last Update Posted: 2019-11-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 200

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bioseal	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Incidence of adverse events	Up to 30(±7)Days	Incidence of adverse events
Incidence of surgical site infections (SSI)	Up to 30(± 7) days	Incidence of surgical site infections (SSI) according to Surgical Site Infection Infection Prevention and Control Guideline (MOH) criteria
Incidence of CSF leakage	Up to 30(+/-7)Days	Incidence of CSF leakage 30 (±7) days post operatively

Trial Locations

Locations (10)

Xuanwu Hospital Capital Medical University; 🇨🇳 Beijing, Beijing, China

The First Affiliated Hospital of Fujian Medical University; 🇨🇳 Fuzhou, Fujian, China

The Affiliated Hospital of Guizhou Medical University; 🇨🇳 Guiyang, Guizhou, China

The first Affiliated Hospital of Zhengzhou University; 🇨🇳 Zhengzhou, Henan, China

ZhuJiang Hospital of Southern Medical University; 🇨🇳 Guangzhou, Guangdong, China

TongJi Hospital, TongJi Medical College of HUST; 🇨🇳 Wuhan, Hubei, China

The First Affiliated Hospital of Soochow University; 🇨🇳 Suzhou, Jiangsu, China

The Affiliated Hospital of Xuzhou Medical University; 🇨🇳 Xuzhou, Jiangsu, China

The First Hospital of Jilin University; 🇨🇳 Changchun, Jilin, China

Huashan Hospital, Shanghai Medical College, Fudan University; 🇨🇳 Shanghai, Shanghai, China