Efficiency of Amnion Graft to Prevent Intrauterine Adhesions After Hysteroscopic Surgery

Intrauterine Adhesions Clinical Trial

Official title:

Amnion Graft for Preventing Intrauterine Adhesions Following Hysteroscopic Surgery

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02132104
• Other study ID #: CMU-FXH-14-06
• Status: Not yet recruiting
• Phase: N/A
• First received: May 2, 2014
• Last updated: October 20, 2014
• Start date: November 2014
• Est. completion date: November 2016

Study information

• Verified date: October 2014
• Source: Capital Medical University
• Contact: Xuebing Peng, MD
• Phone: 008613901297392
• Email: peng_xue_bing[@]hotmail.com
• Is FDA regulated: No
• Health authority: China: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to evaluate whether human amnion graft reduces the reformation of severe intrauterine adhesions (IUA) following hysteroscopic adhesiolysis.

Description:

Background

IUA is a consequence of trauma to the endometrium, producing partial or complete obliteration in the uterine cavity and/or the cervical canal, resulting in conditions such as menstrual abnormalities, infertility, and recurrent pregnancy loss. The outcome of hysteroscopic adhesiolysis for IUA is significantly affected by recurrence of intrauterine adhesions. The IUA research should be directed toward reduction of adhesion reformation with a view to improve outcome.

The reformation of intrauterine adhesions appears to be directly related to the severity of the adhesions. It has been reported that the recurrence rate for intrauterine adhesions ranges from 3.1% to 23.5% among all cases of intrauterine adhesions and from 20% to 62.5% in those with severe adhesions.

In this study, considering the high recurrent rate in severe IUA, investigator will focus on severe IUA cases.

Up to now several strategies are commonly employed by various investigators after division of intrauterine adhesions:

1. Physical barriers have been used to promote regeneration of the endometrium and prevention of adhesions. The physical barriers include an intrauterine device (IUD), a Foley catheter, a number of modifications of hyaluronic acid and Auto-cross-linked hyaluronic acid gel.

2. Hormonal treatment has been used to promote regeneration of the endometrium.

3. Antibiotic therapy has been used to prevent infection which is a potent trigger for adhesion formation/reformation.

4. Various medications have been described to increase vascular flow to endometrium, such as asprin, nitroglycerine and sildenafil citrate.

There is published data (Amer et al, 2010), which based on a plot prospective, randomised, comparative study that grafting of either fresh or dried amnion is a promising adjunctive procedure for decreasing recurrence of adhesions and encouraging endometrial regeneration after hysteroscopic lysis of severe intrauterine adhesions. However, the study had a small number of patients, the valid conclusion can not be drawn.

In this study, the aim is to compare the safety and the efficacy of insertion of intrauterine balloon + hormonal treatment with or without grafting amnion to prevent intrauterine adhesion formation/reformation following division of intrauterine adhesions.

Study Design

Patients with severe IUA are enrolled according to the classification of intrauterine adhesion by American Fertility Society.

208 patients with severe IUA were chosen at random and divided equally into those who received amnion graft, following hysteroscopic adhesiolysis (treatment groups) and to those who did not receive the amnion graft (control groups).

Intervention

Following hysteroscopic adhesiolysis, patients will be randomised to have a Foley balloon with or without amnion graft into the uterine cavity. Hormones therapy has been used after surgical treatment both in treatment groups and control groups. A second look and a third look hysteroscopy will be performed about 4 and 12 weeks after the initial operative hysteroscopy. The amount of adhesions, if any, during the initial and reexamine hysteroscopies will be scored.

Power calculation

The investigators' retrospective pilot study data showed that the recurrent rate of severe IUA is around 30% in amnion treatment groups, and around 47.5% in control groups. According to these data, investigators calculated the sample sizes of this study by using Cochran-Mantel-Haenszel test with software PASS 11. Investigators will recruit 104 patients in each group.

Group sample sizes of 104 in group one and 104 in group two achieve 85% power to detect a difference between the group proportions of -0.2000. The group two proportion is 0.5000. The group one proportion is assumed to be 0.5000 under the null hypothesis and 0.3000 under the alternative hypothesis. The test statistic used is the two-sided Z test (unpooled). The significance level of the test was targeted at 0.0500. The significance level actually achieved by this design is not available.

Statistics

Safety and efficacy were evaluated by software NCSS-PASS, using Two Independent Proportions (Non-Null Case) Power Analysis.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 208
• Est. completion date: November 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• patients scheduled for adhesiolysis of intrauterine adhesions

• patients willing to undergo followed hysteroscopy about 4 and 12 weeks after the surgery to assess the reformation of intrauterine adhesions.

• Written, informed consent obtained.

Exclusion Criteria:

• ongoing pregnancy

• Peroperative fever or infections

• Malignancy

• Precious pelvic inflammatory disease

• Uterine fibroid (>3cm size)

• endometriosis

• Contraindications for anesthesia

• Not able to read and/or understand informed consent.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Intrauterine Adhesions
• Tissue Adhesions

Intervention

Procedure:
• Uterine application of amnion membrane
Uterine application of amnion membrane following hysteroscopic adhesiolysis.

Device:
• Foley balloon
Uterine application of Foley balloon

Drug:
• Femoston
Hormones treatment after surgery.

Locations

Country	Name	City	State
China	Fu Xing Hospital, Capital Medical University	Beijing
China	Fu Xing Hospital, Capital Medical University	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Capital Medical University

Country where clinical trial is conducted

China, 

References & Publications (4)

Amer MI, Abd-El-Maeboud KH, Abdelfatah I, Salama FA, Abdallah AS. Human amnion as a temporary biologic barrier after hysteroscopic lysis of severe intrauterine adhesions: pilot study. J Minim Invasive Gynecol. 2010 Sep-Oct;17(5):605-11. doi: 10.1016/j.jmig.2010.03.019. Epub 2010 Jun 23. — View Citation

Amer MI, Abd-El-Maeboud KH. Amnion graft following hysteroscopic lysis of intrauterine adhesions. J Obstet Gynaecol Res. 2006 Dec;32(6):559-66. — View Citation

The American Fertility Society classifications of adnexal adhesions, distal tubal occlusion, tubal occlusion secondary to tubal ligation, tubal pregnancies, müllerian anomalies and intrauterine adhesions. Fertil Steril. 1988 Jun;49(6):944-55. — View Citation

Yu D, Wong YM, Cheong Y, Xia E, Li TC. Asherman syndrome--one century later. Fertil Steril. 2008 Apr;89(4):759-79. doi: 10.1016/j.fertnstert.2008.02.096. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	safety of intrauterine application of amnion membrane	patients treated by amnion membrane following their hysteroscopic procedure were followed for immediate and late adverse effect: fever, abnormal vaginal discharge, pelvic pain, increased intrauterine adhesion formation upon follow up and changes in menstrual pattern.	3 months	Yes
Secondary	efficacy of intrauterine application of amnion graft in reducing adhesion formation following hysteroscopic adhesiolysis.	intrauterine adhesions were assessed and graded according to the American Fertility Society (AFS) score upon hysteroscopy follow up 4 and 12 weeks following initial treatment.	3 months	No