Heparin Solution Versus Anti-adhesion Barrier Gel for Intrauterine Adhesions Prevention After Operative Hysteroscopy

Intrauterine Adhesions Prevention: the Use of Heparin Solution Compared to Application of Anti-adhesion Barrier Gel After Operative Hysteroscopy

The aim of this study is to compare the efficacy of intrauterine application of heparin solution to the use of hyaluronic acid barrier gel for the prevention of intrauterine adhesion formation after operative hysteroscopy.

Study Overview

• Status: Recruiting
• Conditions: Intrauterine Adhesion
• Intervention / Treatment: Drug: Heparin solution; Drug: Anti-adhesion barrier gel

Detailed Description

In this trial the investigators aim to evaluate and compare the effect of heparin solution to anti-adhesive hyaluronic barrier gel administration immediately after operative hysteroscopy on post-surgical complications (incidence, extent and severity of intrauterine adhesions, abnormal menstrual cycle pattern) and fertility.

Patients undergoing operative hysteroscopy will be identified and invited to participate in the trial. At 4 to 8 weeks after the initial surgery, a follow-up, diagnostic hysteroscopy will be performed to identify indications for subsequent operative procedure and classify intrauterine adhesions according to extent of uterine cavity affected and type of formation found. Data on subsequent persistent irregular menstrual bleeding and pregnancy success up to 12 months following treatment will also be collected.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Georgi Stamenov; Phone Number: +359888269839; Email: g.stamenov1@abv.bg

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1373
    • Recruiting
    • Nadezhda Women's Health Hospital
    • Contact: Zornitsa Buteva, MD; Phone Number: +359895603362; Email: zornitsa@dr.buteva.com
  • Sofia, Bulgaria, 1330
    • Recruiting
    • Nadezhda Women's Health Hospital
    • Contact: Georgi Stamenov, MD; Phone Number: 359 888269839; Email: g.stamenov@abv.bg
    • Contact: Margarita Ruseva, MSc; Phone Number: 359 889150267; Email: margarita.ruseva@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• female sex
• indication for operative hysteroscopy including one or more of the following:
• infertility,
• irregular bleeding,
• oligo-/amenorrhea,
• Asherman syndrome,
• G0-G3 fibroids,
• dysmorphic uterus.

Exclusion Criteria:

• ongoing pregnancy,
• genital cancer,
• pelvic inflammatory disease,
• excessive uterine bleeding.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Heparin solution; Administration of 3 ml heparin solution into the uterine cavity via a syringe immediately post operative hysteroscopy.	Drug: Heparin solution; 3 ml saline solution containing 5000 IU heparin.; Other Names: HEP
Active Comparator: Anti-adhesion barrier gel; Intrauterine application of 2 ml biodegradable anti-adhesion barrier gel immediately post operative hysteroscopy.	Drug: Anti-adhesion barrier gel; 2 ml biodegradable barrier gel containing sodium hyaluronate (10 mg/ml), sodium chloride (8.5 mg/ml), disodium hydrogen phosphate (0.34mg/ml), sodium dihydrogen phosphate (0.14 mg/ml) and water for injection (QS to weight).; Other Names: AAB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with post-operative intrauterine adhesion formation	Incidence and severity of intrauterine adhesions identified at follow-up diagnostic hysteroscopy as assessed according to Valle and Sciarra's classification of intrauterine synaechia	4 to 8 weeks post treatment
Number of patients with need for subsequent operative hysterectomy	Pathological findings at second-look hysteroscopy taken as indication for successive uterine surgery	4 tot 8 weeks post treatment
Number of patients with persistent irregular menstrual bleeding	Recurring abnormal menstrual cycle patterns identified post initial surgery	up to 12 months post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with fertility improvement	Successful pregnancy post surgical procedure	up to 12 months post treatment

Collaborators and Investigators

• Sponsor: Nadezhda Women's Health Hospital

Publications and helpful links

General Publications

• Valle RF, Sciarra JJ. Intrauterine adhesions: hysteroscopic diagnosis, classification, treatment, and reproductive outcome. Am J Obstet Gynecol. 1988 Jun;158(6 Pt 1):1459-70. doi: 10.1016/0002-9378(88)90382-1.
• Healy MW, Schexnayder B, Connell MT, Terry N, DeCherney AH, Csokmay JM, Yauger BJ, Hill MJ. Intrauterine adhesion prevention after hysteroscopy: a systematic review and meta-analysis. Am J Obstet Gynecol. 2016 Sep;215(3):267-275.e7. doi: 10.1016/j.ajog.2016.05.001. Epub 2016 May 10.
• Nappi C, Di Spiezio Sardo A, Greco E, Guida M, Bettocchi S, Bifulco G. Prevention of adhesions in gynaecological endoscopy. Hum Reprod Update. 2007 Jul-Aug;13(4):379-94. doi: 10.1093/humupd/dml061. Epub 2007 Apr 23.
• van Wessel S, Hamerlynck T, Schutyser V, Tomassetti C, Wyns C, Nisolle M, Verguts J, Colman R, Weyers S, Bosteels J. Anti-adhesion Gel versus No gel following Operative Hysteroscopy prior to Subsequent fertility Treatment or timed InterCourse (AGNOHSTIC), a randomised controlled trial: protocol. Hum Reprod Open. 2021 Feb 16;2021(1):hoab001. doi: 10.1093/hropen/hoab001. eCollection 2021.
• Lee WL, Liu CH, Cheng M, Chang WH, Liu WM, Wang PH. Focus on the Primary Prevention of Intrauterine Adhesions: Current Concept and Vision. Int J Mol Sci. 2021 May 13;22(10):5175. doi: 10.3390/ijms22105175.

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2022
• Primary Completion (Estimated): February 14, 2026
• Study Completion (Estimated): February 28, 2026

Study Registration Dates

• First Submitted: February 16, 2022
• First Submitted That Met QC Criteria: February 16, 2022
• First Posted (Actual): February 25, 2022

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: heparin; hyaluronic acid; intrauterine adhesion; operative hysteroscopy; anti-adhesion barrier gel
• Additional Relevant MeSH Terms: Pathologic Processes; Fibrosis; Cicatrix; Tissue Adhesions; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin
• Other Study ID Numbers: 3/11022022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No