The Efficacy and Safety Study of a New Cross-linked Hyaluronan Hydrogel in the Reduction of Postsurgical Peritoneal Adhesions (BAP)

The Efficacy and Safety of a New Cross-linked Hyaluronan Hydrogel in the Reduction of Postsurgical Adhesions After Laparoscopic Gynecological Surgery: a Randomized Controlled Trial

The purpose of this study was to determine whether the new crosslinked hyaluronan hydrogel was safe to use, and was effective for the prevention/reduction of adhesion formation following gynecological surgery

Study Overview

• Status: Completed
• Conditions: Adhesions; Myomas; Ovary Cysts; Endometriotic Cysts
• Intervention / Treatment: Other: Saline; Device: Cross-linked Hyaluronan Hydrogel

Detailed Description

Postsurgical adhesions are a common medical complication of gynecologic and pelvic surgeries, and are frequently associated with chronic or recurrent pelvic pain, intestinal obstruction and infertility. This randomized, controlled, multicenter, clinical study was designed to evaluate the safety and performance of the new crosslinked hyaluronan hydrogel versus the standard of care for the reduction of postoperative adhesions in subjects undergoing laparoscopic surgeries. Subjects were scheduled to return at 9 weeks after the initial surgical procedure. At that time, a second-look laparoscopy was performed for postsurgical adhesion assessment. Adhesions were graded using a modified American Fertility Society (mAFS) scoring system.

• Study Type: Interventional
• Enrollment (Actual): 216
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100034
      • Peking University First Hospital
    • Beijing, Beijing, China, 100020
      • Beijing Chao-Yang Hospital
    • Beijing, Beijing, China, 100730
      • Beijing Hospital
    • Beijing, Beijing, China, 100029
      • China-Japan Friendship Hospital
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • The Second Hospital of Hebei Medical University
  • Hunan
    • Changsha, Hunan, China, 410013
      • The Third Xiangya Hospital
  • Shandong
    • Jinan, Shandong, China, 250012
      • Qilu hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female.
• Aged 18-45 years.
• Been scheduled for removal of myomas, ovary cysts, endometriotic cysts or adhesions.
• Been willing to comply with all aspects of the treatment and evaluation schedule.
• Agreed to a second-look laparoscopic procedure to assess and lyse any adhesions formed at 9 weeks following the primary surgery.
• Provided voluntary written informed consent.

Exclusion Criteria:

• Acute or severe infection.
• Autoimmune diseases such as diabetes etc.
• Abnormal liver/renal and cardiovascular function
• Abnormal blood coagulation
• Medical histories of peripheral vascular disease, alcohol or drug abuse, and mental illness.
• Known or suspected intolerance or hypersensitivity to hyaluronan or its derivatives.
• Concurrent use of systemic antiinflammatory drugs.
• Clinical evidence of cancer.
• Use of anticoagulant, fibrin glue, other thrombogenic agents, or any other anti-adhesion agent during the procedure.
• Concurrent peritoneal grafting or tubal implantation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control Arm; Standard of care for post-operative adhesion prevention included irrigation of tissues and lavage of all fluids with saline placebo following surgery	Other: Saline; On the day of initial surgery
Experimental: Cross-linked Hyaluronan Hydrogel Arm; HyaRegen	Device: Cross-linked Hyaluronan Hydrogel; On the day of the initial surgery; Other Names: HyaRegen; Self Cross-linked Hyaluronan Gel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The adhesion incidence under moderate/severe category	The patient percentage with modified American Fertility Society (mAFS) score (ovaries and tubes) more than 4 points.	9 weeks following primary laparoscopic gynecological surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
modified American Fertility Society (mAFS) score	modified American Fertility Society (mAFS) score of ovaries/tubes	9 weeks following primary laparoscopic gynecological surgery
Adhesion extent	Adhesion extent of ovaries/tubes	9 weeks following primary laparoscopic gynecological surgery
Adhesion severity	Adhesion severity of ovaries/tubes	9 weeks following primary laparoscopic gynecological surgery
The adhesion incidence under moderate/severe category	The patient percentage with modified American Fertility Society (mAFS) score (throughout abdominopelvic cavity) more than 4 points.	9 weeks following primary laparoscopic gynecological surgery
modified American Fertility Society (mAFS) score	modified American Fertility Society (mAFS) score (throughout abdominopelvic cavity)	9 weeks following primary laparoscopic gynecological surgery
Adhesion extent	Adhesion extent (throughout abdominopelvic cavity)	9 weeks following primary laparoscopic gynecological surgery
Adhesion severity	Adhesion severity (throughout abdominopelvic cavity)	9 weeks following primary laparoscopic gynecological surgery
Adverse events	Safety evaluation was based on clinical laboratory tests, the type and severity of adverse events recorded throughout the study, etc.	Up to 9 weeks

Collaborators and Investigators

• Sponsor: BioRegen Biomedical (CHangzhou) Co., Ltd
• Investigators: Principal Investigator: Zhenyu Zhang, MD, PhD, Beijing Chao Yang Hospital

Publications and helpful links

General Publications

• Liu C, Lu Q, Zhang Z, Xue M, Zhang Y, Zhang Y, Wang H, Li H, Zhou Y, Zhang Z, Li W; HyaRegen Adhesion Study Group. A Randomized Controlled Trial on the Efficacy and Safety of a New Crosslinked Hyaluronan Gel in Reducing Adhesions after Gynecologic Laparoscopic Surgeries. J Minim Invasive Gynecol. 2015 Jul-Aug;22(5):853-63. doi: 10.1016/j.jmig.2015.04.011. Epub 2015 Apr 20.

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: June 13, 2014
• First Submitted That Met QC Criteria: June 16, 2014
• First Posted (Estimate): June 18, 2014

Study Record Updates

• Last Update Posted (Estimate): June 18, 2014
• Last Update Submitted That Met QC Criteria: June 16, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: Adhesions; Hyaluronan; Clinical outcomes; Gynaecological surgery
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Pathological Conditions, Anatomical; Fibrosis; Cicatrix; Tissue Adhesions; Cysts; Physiological Effects of Drugs; Immunologic Factors; Protective Agents; Adjuvants, Immunologic; Viscosupplements; Hyaluronic Acid
• Other Study ID Numbers: FNL-2011-05