Postoperative Intermittent Intrauterine Balloon Dilatation Therapy.

• ClinicalTrials.gov Identifier: NCT03131596
• Recruitment Status: Completed
• First Posted: April 27, 2017
• Results First Posted: September 13, 2019
• Last Update Posted: September 13, 2019
• Sponsor: Fu Xing Hospital, Capital Medical University
• Information provided by (Responsible Party): Xiaoyu Shi, Fu Xing Hospital, Capital Medical University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Intrauterine Adhesion	Procedure: IUB dilatation therapy	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Masking Description: Both surgeons conducting the hysteroscopic surgery and follow-up hysteroscopy were blinded to the patient group allocation.
• Primary Purpose: Prevention
• Official Title: Prevention of Postoperative Adhesion Reformation by Intrauterine Balloon Therapy: a Randomized Controlled Trial
• Actual Study Start Date: May 15, 2017
• Actual Primary Completion Date: November 15, 2017
• Actual Study Completion Date: November 15, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: IUB dilatation therapy; The patient will have Foley-catheter intrauterine balloon dilatation 2 weeks and 6 weeks after hysteroscopic adhesiolysis. A second-look hysteroscopy will be carried out in the early proliferative phase 4 weeks after the surgery and third-look hysteroscopy will be carried out 8 weeks after the surgery.	Procedure: IUB dilatation therapy; A Foley catheter (size 14fr) will be prepared by cutting the excess catheter tip protruding beyond the balloon prior to insertion into the uterine cavity. Once the catheter has reached the fundus, 3-4.5mls of saline will be slowly introduced into the balloon under ultrasound guidance, in order to directly visualize the distention of the cavity and division of any intrauterine adhesions, if present.
No Intervention: control group; Patient will not undergo any balloon therapy. A second-look hysteroscopy will be carried out in the early proliferative phase 4 weeks after the surgery and third-look hysteroscopy will be carried out 8 weeks after the surgery.

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Adhesion Reformation (American Fertility Society Score of Greater Than 0) 8 Weeks Later After the Index Surgery [ Time Frame: at 8 weeks post-operation ]
   The American Fertility Society (AFS) score ranges from 0-12, while represented the severity of the adhesions. Mild 1-4, Moderate 5-8, Severe 9-12. The lower the AFS score is, the better the prognosis the patient is. When the surgery was finished the AFS score should be 0. The reformation of intrauterine adhesions was evaluated by third-look hysteroscopy, if the score was greater than 0, a adhesion reformation was considered.
2. The American Fertility Society Score 8 Weeks After Operation [ Time Frame: at 8 weeks post-operation ]
   The American Fertility Society(AFS) score of each group was evaluated again at third-look hysteroscopy in order to reflect the efficacy of the treatment. The original AFS score was recorded in baseline characteristics part. The AFS score ranges from 0-12, while represented the severity of the adhesions. Mild 1-4, Moderate 5-8, Severe 9-12. The lower the AFS score is, the better the prognosis the patient is. When the surgery was finished the AFS score score should be 0.
3. Pictorial Blood Loss Assessment Chart Score 8 Weeks After Operation [ Time Frame: at 8 weeks post-operation ]

   The Pictorial Blood Loss Assessment Chart (PBAC) score was used to represent the menstrual flow volume of the patient. The PBAC score was evaluated again at 8 weeks after surgery. A higher PBAC score after hysteroscopic adhesiolysis means a better outcome.The PBAC score of a normal women usually range from 30-100 points.

   The minium value of PBAC score is 0, which means the patient is amenorrhea. The maximum value of PBAC score is 1000.

   We measured the score before and 8 weeks after the operation in order to assess if there was any improvement (higher than before) in menstrual flow.

Secondary Outcome Measures :

1. Pregnancy Outcome Within 12 Months Follow-up After Third Look Hysteroscopy [ Time Frame: within 12 months after third look hysteroscopy(8 weeks post-operation) ]
   number of patients who have pregnancy, miscarriage and ectopic pregnancy within12 months follow-up

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 40 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

China, Beijing

Fu Xing Hospital

Beijing, Beijing, China, 100038

Sponsors and Collaborators

Fu Xing Hospital, Capital Medical University

Investigators

• Study Chair: Tinchiu Li; Fuxing Hospital,Capital Medical University，China

  Study Documents (Full-Text)

Documents provided by Xiaoyu Shi, Fu Xing Hospital, Capital Medical University:

Study Protocol and Statistical Analysis Plan  [PDF] March 1, 2017

More Information

Publications:

Saravelos SH, Li TC. Ultrasound-guided treatment of intrauterine adhesions in the outpatient setting. Ultrasound Obstet Gynecol. 2017 Aug;50(2):278-280. doi: 10.1002/uog.16218.

March CM. Intrauterine adhesions. Obstet Gynecol Clin North Am. 1995 Sep;22(3):491-505. Review.

ASHERMAN JG. Traumatic intra-uterine adhesions. J Obstet Gynaecol Br Emp. 1950 Dec;57(6):892-6.

ASHERMAN JG. Amenorrhoea traumatica (atretica). J Obstet Gynaecol Br Emp. 1948 Feb;55(1):23-30.

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.

Orhue AA, Aziken ME, Igbefoh JO. A comparison of two adjunctive treatments for intrauterine adhesions following lysis. Int J Gynaecol Obstet. 2003 Jul;82(1):49-56.

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.

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. Review.

Saravelos, S.H. & Li, TC. Gynecol Surg (2016) 13: 403. doi:10.1007/s10397-016-0972-2

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Xiaoyu Shi, principal investigator, Fu Xing Hospital, Capital Medical University
• ClinicalTrials.gov Identifier: NCT03131596
• Other Study ID Numbers: 2016FXHEC-KY036
• First Posted: April 27, 2017
• Results First Posted: September 13, 2019
• Last Update Posted: September 13, 2019
• Last Verified: August 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Xiaoyu Shi, Fu Xing Hospital, Capital Medical University:

Intrauterine Adhesion; Hysteroscopy; Intrauterine balloon; Reformation; Prevention

Additional relevant MeSH terms:

Tissue Adhesions; Cicatrix; Fibrosis; Pathologic Processes