Clinical trial NCT03131596: Postoperative Intermittent Intrauterine Balloon Dilatation Therapy.
Official title: Prevention of Postoperative Adhesion Reformation by Intrauterine Balloon Therapy: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Intrauterine Adhesion
Keywords: Intrauterine Adhesion
Hysteroscopy
Intrauterine balloon
Reformation
Prevention
Lead sponsor: Fu Xing Hospital, Capital Medical University
Sponsor class: OTHER
First posted: 2017-04-27
Enrollment: 200
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: In this prospective, randomized, controlled study, the investigators wish to determine the efficacy of intrauterine balloon (IUB) dilatation in the prevention of adhesion reformation when compared with the conventional management.

Detailed description: Patients

The patients will be recruited from the Hysteroscopy Center of the Fuxing Hospital, Beijing, China. Before the surgery all patients with suspected Asherman syndrome will undergo preoperative evaluations, including a detailed history of the menstrual pattern, any previous intrauterine surgery, and reproductive history, as well as trans-vaginal ultrasonography. The severity and extent of intrauterine adhesions will be scored according to a classification system recommended by the American Fertility Society (AFS) (1988 version). The inclusion criteria include \[1\] women aged 18-40 years; \[2\] moderate to severe intrauterine adhesion (AFS score≥5); \[3\] first episode of hysteroscopic adhesiolysis in FuXing hospital; \[4\] written consent obtained; and \[5\] agreement to have second-look and an optional third-look hysteroscopy. The exclusion criteria include \[1\] minimal adhesion (AFS score \<5) and \[2\] previous hysteroscopic adhesiolysis in FuXing hospital.

Study Design

After the completion of hysteroscopic adhesiolysis, recruited patients will be randomized to one of the two treatment groups by computer-generated numbers: \[1\] having a Foley-catheter intrauterine balloon dilatation 2 weeks and 6 weeks after hysteroscopic adhesiolysis; \[2\] the control group without any additional treatment. A second-look hysteroscopy will be carried out in the early proliferative phase 4 weeks after the surgery and an optional third-look hysteroscopy will be carried out 8 weeks after the surgery.

Power Calculation

On the basis of the results of the two published retrospective cohort studies comparing the balloon and hormone therapy group (control group) in the prevention of adhesion reformation, we estimate that the adhesion reformation rate in the balloon group to be 20% and in the control group to be 45%. Accepting a type 1 error of 0.05, and a type 2 error of 0.10, the number of subjects in each arm of the randomized, controlled trial would be 79. Assuming that the dropout rate to be 20%, the total number of subject to be recruited would be 100 in each arm.

Procedure

Surgical procedure

The surgery will be carried out by one of two experienced hysteroscopic surgeons with the use of a 8.5-mm rigid hysteroscope (Olympus) with 0.9% normal saline infusion under 120-150 mmHg pressure. The procedure will be performed under general anesthesia in a day surgery unit. Ultrasonographic guidance will be routinely used. Once the extent and severity of uterine adhesion has been assessed, the adhesions will be divided with the use of bipolar instrument until normal uterine anatomy is achieved.

Postoperative treatments

All subjects will be treated with oral antibiotics(Cefaclor 0.375 mg twice daily Tianjin Central Pharmaceutical Co Ltd., Tianjin, China.) for 5-7 days. In all cases hormone therapy also began from the day of operation, consisting of estradiol valerate at a dose of 4 mg/d for 21 days, with the addition of dydrogesterone at a dose of 10 mg/d for the last 7 days of the estrogen therapy. After the withdrawal bleed, the hormone therapy was repeated for a further two cycles, i.e. 3 months in total. Second-look hysteroscopy will be carried out in the early proliferative phase, 4 weeks after the initial operation; a third-look hysteroscopy will be carried out 8 weeks after the initial operation. After assessment of the extent and severity of any reformed adhesion, hysteroscopic adhesiolysis will also be carried out at the time of the second-look procedure, if adhesion has recurred. The surgeon who performs the second-look and third-look hysteroscopy will be blinded to the randomization.

IUB dilatation

IUB dilatation therapy will be performed using a Foley catheter(14fr) and according to the methodology published in the literature. This will be prepared by cutting the catheter tip protruding beyond the balloon. Once the catheter has reached the fundus, 3-4.5mls of saline will be slowly infiltrated into the balloon under ultrasound guidance in order to distend the cavity, thereby separating any reformed intrauterine adhesions.

Statistical Analysis

Intention-to-treat analysis was conducted primarily on all outcomes for all randomized subjects. Numerical data with normal distribution were presented as the mean ± standard deviation, whereas data with skewed distribution were presented as the median (interquartile range). The Student t test was used to compare normally distributed data between two groups and paired t test was used to compare normally distributed data within two groups. The Mann-Whitney U test was used to compare data with skewed distribution. Contingency table analysis and the χ2 test were used to compare categorical data. A p value of \< 0.05 was considered statistically significant. All statistical analysis was carried out with the use of SPSS 21.0.

Outcome measures

The primary outcome measure was defined as the AFS score at each follow-up, including the adhesion reformation rate, in addition to the menstrual improvement, which was evaluated according to Pictorial Blood Loss Assessment Chart (PBAC) score.

Secondary outcomes included pregnancy rate, miscarriage rate and ectopic rate.

Data processing and analysis

The investigators will ensure the confidentiality of sensitive data by minimizing the number of personnel who handle subject data. In addition, computer data will be encrypted as required to maximize security, while paper documents will be locked in filing cabinets, with only authorized personnel having access to the information.

Ethical considerations

IUB dilatation has been published as a novel technique with no untoward complications identified to date. The procedure will be performed according to the methodology available in the literature and the study has gained approval from the local ethical committee.

Consent

All subjects will be given a detailed explanation of the study and sufficient time to consider their participation. A written consent form will be signed by the patient and retained in the confidential records.

Eligibility criteria: Inclusion Criteria:

1. women aged 18-40 years;
2. moderate to severe intrauterine adhesion (AFS score≥5);
3. no previous history of hysteroscopic adhesiolysis in our hospital;
4. written consent obtained
5. agreement to have second-look and third-look hysteroscopy.

Exclusion Criteria:

1. minimal adhesion (AFS score \<5);
2. previous hysteroscopic adhesiolysis in our hospital.

Primary outcomes:
measure: Number of Participants With Adhesion Reformation (American Fertility Society Score of Greater Than 0) 8 Weeks Later After the Index Surgery
timeFrame: at 8 weeks post-operation
measure: The American Fertility Society Score 8 Weeks After Operation
timeFrame: at 8 weeks post-operation
measure: Pictorial Blood Loss Assessment Chart Score 8 Weeks After Operation
timeFrame: at 8 weeks post-operation
Secondary outcomes:
measure: Pregnancy Outcome Within 12 Months Follow-up After Third Look Hysteroscopy
timeFrame: within 12 months after third look hysteroscopy(8 weeks post-operation)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Fu Xing Hospital
state: Beijing
Study officials:
affiliation: Fuxing Hospital,Capital Medical University，China
name: Tinchiu Li
role: STUDY_CHAIR
References:
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citation: March CM. Intrauterine adhesions. Obstet Gynecol Clin North Am. 1995 Sep;22(3):491-505.
citation: ASHERMAN JG. Traumatic intra-uterine adhesions. J Obstet Gynaecol Br Emp. 1950 Dec;57(6):892-6. doi: 10.1111/j.1471-0528.1950.tb06053.x. No abstract available.
citation: ASHERMAN JG. Amenorrhoea traumatica (atretica). J Obstet Gynaecol Br Emp. 1948 Feb;55(1):23-30. doi: 10.1111/j.1471-0528.1948.tb07045.x. No abstract available.
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citation: Saravelos SH, Jayaprakasan K, Ojha K, Li TC. Assessment of the uterus with three-dimensional ultrasound in women undergoing ART. Hum Reprod Update. 2017 Mar 1;23(2):188-210. doi: 10.1093/humupd/dmw040.
citation: Grimbizis GF, Di Spiezio Sardo A, Saravelos SH, Gordts S, Exacoustos C, Van Schoubroeck D, Bermejo C, Amso NN, Nargund G, Timmermann D, Athanasiadis A, Brucker S, De Angelis C, Gergolet M, Li TC, Tanos V, Tarlatzis B, Farquharson R, Gianaroli L, Campo R. The Thessaloniki ESHRE/ESGE consensus on diagnosis of female genital anomalies. Gynecol Surg. 2016;13:1-16. doi: 10.1007/s10397-015-0909-1. Epub 2015 Nov 4.
citation: Shi X, Saravelos SH, Zhou Q, Huang X, Xia E, Li TC. Prevention of postoperative adhesion reformation by intermittent intrauterine balloon therapy: a randomised controlled trial. BJOG. 2019 Sep;126(10):1259-1266. doi: 10.1111/1471-0528.15843. Epub 2019 Jul 18.