- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03131596
Postoperative Intermittent Intrauterine Balloon Dilatation Therapy.
Prevention of Postoperative Adhesion Reformation by Intrauterine Balloon Therapy: a Randomized Controlled Trial
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Beijing
-
Beijing, Beijing, China, 100038
- Fu Xing Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- women aged 18-40 years;
- moderate to severe intrauterine adhesion (AFS score≥5);
- no previous history of hysteroscopic adhesiolysis in our hospital;
- written consent obtained
- agreement to have second-look and third-look hysteroscopy.
Exclusion Criteria:
- minimal adhesion (AFS score <5);
- previous hysteroscopic adhesiolysis in our hospital.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / 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.
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
at 8 weeks post-operation
|
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.
|
at 8 weeks post-operation
|
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. |
at 8 weeks post-operation
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
within 12 months after third look hysteroscopy(8 weeks post-operation)
|
Collaborators and Investigators
Investigators
- Study Chair: Tinchiu Li, Fuxing Hospital,Capital Medical University,China
Publications and helpful links
General Publications
- 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.
- March CM. Intrauterine adhesions. Obstet Gynecol Clin North Am. 1995 Sep;22(3):491-505.
- 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.
- 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.
- 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.
- 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. No abstract available.
- 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.
- 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. doi: 10.1016/s0020-7292(03)00030-4.
- Saravelos, S.H. & Li, TC. Gynecol Surg (2016) 13: 403. doi:10.1007/s10397-016-0972-2
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2016FXHEC-KY036
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Intrauterine Adhesion
-
Hua DuanRecruitingIntrauterine Adhesion | Database for Intrauterine Adhesion | Risk Factors for Intrauterine Adhesion | Risk Stratification and Prognostic AssessmentChina
-
The Fourth Affiliated Hospital of Zhejiang University...Recruiting
-
Rejoni Inc.CompletedIntrauterine AdhesionUnited States
-
Ain Shams Maternity HospitalCompletedIntrauterine AdhesionEgypt
-
Fu Xing Hospital, Capital Medical UniversityBeijing Tiantan HospitalUnknown
-
Rejoni Inc.RecruitingIntrauterine AdhesionUnited States
-
Limin FengRecruitingIntrauterine AdhesionChina
-
Fu Xing Hospital, Capital Medical UniversityRecruitingIntrauterine AdhesionChina
-
Second Affiliated Hospital, School of Medicine,...Shanghai iCELL Biotechnology Co., Ltd, Shanghai, ChinaRecruitingIntrauterine AdhesionChina
-
WomedCompletedIntrauterine AdhesionBelgium, France, Netherlands
Clinical Trials on IUB dilatation therapy
-
Fu Xing Hospital, Capital Medical UniversityBeijing Tiantan HospitalUnknownIntrauterine AdhesionChina
-
Ocon Medical Ltd.RecruitingHeavy Menstrual BleedingIsrael, Georgia
-
University Hospital, GhentCompletedDiabetic Angiopathies | Intermittent ClaudicationBelgium
-
Wiebe, Ellen, M.D.Completed
-
Ocon Medical Ltd.RecruitingHeavy Menstrual BleedingIsrael
-
University of Cape TownCompletedTracheal StenosisSouth Africa
-
Karolinska University HospitalSahlgrenska University Hospital, Sweden; University Hospital, Linkoeping; Lund... and other collaboratorsUnknownDelayed Gastric Emptying | Esophagectomy | No Signs of Cancer RecurrenceSweden
-
Recherches et etudes en sciences sociales et sante...Unknown
-
Biosensors Europe SACompleted