Safety and Efficacy of Intrauterine Biological Barrier on Postoperative Adhesion After Hysteroscopic Adhesiolysis

Study Overview
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Brief Summary
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To evaluate the safety and efficacy of Intrauterine Biological Barrier developed and produced by Chengdu TopRegMed Medical Technology Co., Ltd on postoperative adhesion after Hysteroscopic Adhesiolysis.

Detailed Description
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This study is a prospective, multicenter, randomized, parallel positive-control, non-inferior clinical trial, with the purpose to evaluate the efficacy and safety of Intrauterine Biological Barrier for the prevention or reduction of intrauterine adhesions after Hysteroscopic Adhesiolysis. The trial will be conducted at six clinical centers with 264 subjects who meet all the inclusion/ exclusion criteria. Subjects will be randomly assigned to the experimental group and the control group in a 1:1 ratio. Subjects in the test group were treated with Intrauterine Biological Barrier (IBB) made by Chengdu TopRegMed Medical Technology Co. , Ltd. , while the patients in the positive control group were treated with commercially approved Intrauterine Adhesion Barrier Gel for uterine cavity made by Changzhou Bioregen biopharmaceutical Co. , Ltd. . Subjects will be followed up for 12 months (360 days ± 30 days) after implantation. 73-days (± 12 days) after operation, the safety and effectiveness of IBB will be evaluated by demonstrating non-inferiority to commercially approved gel. If test group is non-inferiority, further study will be performed to explore whether the safety and effectiveness of the IBB is better than the control group in the aspect of the recurrence rate of intrauterine adhesion, types of intrauterine adhesion, postoperative endometrial repair, menstrual recovery and 1-year pregnancy rate.

Official Title
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Safety and Efficacy of Intrauterine Biological Barrier on Postoperative Adhesion After Hysteroscopic Adhesiolysis: a Prospective, Multicentre, Randomized, Positive Parallel Controlled, Non-inferiority, Clinical Trail

Conditions
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Intrauterine Adhesion

Intervention / Treatment
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* Device: Intrauterine Biological Barrier
* Device: Intrauterine Adhesion Barrier Gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: （1）Age, yr20-40 (including boundary value), Female （2）Normal ovarian reserve function (FSH<10U/ml，AMH>2ng/ml) （3）Who suffered from moderate to severe intrauterine adhesions (AFS ≥ 5 points) diagnosed by hysteroscopy, and prepared to be treated by Hysteroscopic adhesiolysis （4）Both husband and wife have fertility intention during treatment （5）Accept to treatment and follow-up visits, Sign the ICF Exclusion Criteria: （1）Severe systemic diseases, contraindications of surgical and cycle （2）Inflammation of reproductive tract, genital tuberculosis, pelvic infection, tumor of reproductive organs （3）Systemic diseases cause uterine bleeding （4）Allergic to hyaluronic acid or components （5）Allergic to swine sources medical device, or refuse to swine sources medical device for religious, ethnic and other reasons （6）Insufficient uterine cavity volume after Hysteroscopic adhesiolysis to place Intrauterine Biological Barrier or inject Intrauterine Adhesion Barrier Gel （7）Involved other clinical trial before Hysteroscopic adhesiolysis in 3 months or during the trail （8）Unable to tolerate anesthesia （9）Estrogen medicine was taken within 30 days of Hysteroscopic adhesiolysis （10）Other inadequacy patient assessed by the researchers

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Group<br>Material：Small intestinal submucosa Specifications：A、B、C、D、E Dosage: investigator selects the specification and quantity(dosage) according to the postoperative uterine cavity volume Frequency：one time after the operation Duration：Single-use | Device: Intrauterine Biological Barrier<br>* after Hysteroscopic adhesiolysis，use of Intrauterine Biological Barrier to repair uterine cavity<br>|
| Active Comparator: Control Group<br>Material: auto-crosslinked HA gel Specifications: 1 ml, 1.25 ml, 1.5 ml, 1.75 ml, 2 ml, 2.25 ml, 2.5 ml, 2.75 ml, 3 ml, 3.25 ml, 3.75 ml, 4 ml, 4.25 ml, 4.5 ml, 5 ml, 6 ml, 8ml Dosage: investigator selects the specification and quantity(dosage) according to the postoperative uterine cavity volume Frequency：one time after the operation Duration：Single-use | Device: Intrauterine Adhesion Barrier Gel<br>* after Hysteroscopic adhesiolysis，use of Intrauterine Adhesion Barrier Gel to repair uterine cavity<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effective rate | At second-look hysteroscopy after Hysteroscopic adhesiolysis, the effective rate (%) = (number of cured + number of apparent effect)/total number in the group × 100% | Day 73±12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence rate of adhesions | The Presence of adhesions was determined at second-look hysteroscopy after Hysteroscopic adhesiolysis, and the recurrence rate of adhesions (%) = number of adhesion reoccurrence/total number in the group × 100% | Day 73±12 | 
| Extent of uterine adhesions | The degree of uterine adhesions was assessed intraoperatively and at the second-look hysteroscopy with reference to the ESGE (European Society for Gynecological Endoscopy) criteria | Day 73±12 | 
| Endometrial improvement | Endometrial thickness in millimeter and change values in millimeter by Ultrasonic Diagnostic Equipment Transvaginal Ultrasonic Probe Head at screening and visit 4 | Day -7 to day 1, Day 100±10 | 
| Time of menstrual recovery | Time to first menstruation after Hysteroscopic adhesiolysis | Day 73±12 | 
| Duration of Menstrual recovery | Days of menstrual duration | Day 73±12, Day 100±10 , Day 180±30, Day 360±30 | 
| Menstrual blood volume | Record and evaluate by Pictorial Blood Loss Assessment Chart (PBAC) | Day 73±12, Day 100±10 , Day 180±30, Day 360±30 | 
| Pregnancy rate after operation 1year | Pregnancy rate (%) = number of pregnancies in the group/total number in the group × 100% | Day 360±30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endometrium, Adhesion, Postoperative adhesion, Hysteroscopy, Biological Barrier, Adhesion prevention, Infertility, Hysteroscopic Adhesiolysis