Clinical trial NCT02648698: RCT(Randomized Clinical Trial ) of Antibiotic Therapy in Chronic Endometritis
Official title: A Prospective, Randomized,Controlled Trial on the Effect of Antibiotic Therapy on Endometrial Response in Women With Chronic Endometritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Endometritis
Keywords: chronic endometritis
CD138
antibiotic
conversion rate.
Lead sponsor: Fu Xing Hospital, Capital Medical University
Sponsor class: OTHER
First posted: 2016-01-07
Enrollment: 120
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 120 cases with a diagnosis of chronic endometritis, confirmed by the presence of plasma cells in endometrial biopsy sample identified by immunohistochemical staining using CD138 antibody, have been recruited. The subjects have been randomly divided into two groups, the experimental group have been given antibiotic (Levofloxacin and Tinidazole for 14 days) treatment, the control group did not receive any antibiotic. Initially it was planned for women in the control group to take placebo,but the organization was difficult, so it was changed prior to the start of the study to an open label study. A repeat endometrial biopsy sample have been obtained 2-4 weeks after completion of the antibiotic therapy to assess the response to treatment. The conversion rate will be compared between the two groups

Detailed description: This study will be carried out at the Hysteroscopy centre of the Fuxing Hospital, Capital Medical University ,Beijing, China. A total of 120 women with chronic endometritis who fulfilled the following inclusion criteria will be recruited:

1. CD138 immunohistochemical staining of endometrial specimen showed presence of one or more plasma cells per 10HPF which confirmed chronic endometritis, according to published criteria.
2. women who were pre-menopausal.
3. no evidence of endometrial hyperplasia or malignancy or structural uterine pathology.
4. agreement to have a second endometrial biopsy \~4 weeks after the initial endometrial biopsy.
5. written informed consent obtained

Exclusion Criteria:

1. women who received steroid hormone therapy within one month of recruitment.
2. allergy or suspected allergy to the chosen antibiotic therapy.
3. women who developed any concurrent infection and received any antibiotic therapy during the period of study other than the one prescribed according to the study protocol.

Power calculation: Assuming that the spontaneous CD138 conversion (from positive to negative ) rate is 25% and that the antibiotic therapy results in 60% conversion rate, the total number of subjects required in each arm of the RCT will be 37, accepting a Type I error of 0.05 and a Type II error of 0.1, and assuming a drop-out rate of 20%, 45 subjects will need to be recruited into each arm. Hence, a total of 90 subjects who fulfilled the inclusion criteria will be required.

Recruitment: Women have been recruited form the day case hysteroscopy unit of the Hysteroscopy center, Fuxing Hospital, Beijing, China. The Hysteroscopy center currently carries out \~600 day case hysteroscopy per month. In all cases, endometrial biopsy specimen will be obtained at the time of hysteroscopy for histological evaluation. Since 2013, all endometrial specimens have been routinely examined with the used of CD138 antibody to establish if there is evidence of chronic endometritis, in addition to routine histopathological examination. Previous audit showed that \~15% of subjects had positive staining for CD138 cells.We recruited the initial 132 subjects according to the inclusion and exclusion criteria succesfully from July 2016 to December 2018.

Randomization:Women who had histological confirmation of CE in an endometrial biopsy specimen and who fulfilled the inclusion criteria were randomized into the antibiotic group and control group in a 1:1 ratio using a computer-generated randomization list and sealed opaque envelopes prepared by the first author. The patients were not blinded to the antibiotic treatment. The pathologist who performed the histological evaluation was blinded to the treatment.

Antibiotic therapy: Women who were randomized to the treatment group were given oral Levofloxacin and Tinidazole daily for 14 days.

Women who were randomized to the control group did not receive any antibiotic. Staff Pharmacist dispense medication.

Consent: written informed consent will be obtained

Repeat endometrial biopsy \& histological evaluation: The repeat endometrial biopsy will be performed after completion of the the antibiotic therapy. Immunohistochemical study using CD138 antibody will be performed.

Eligibility criteria: Inclusion Criteria:

1. CD138 immunohistochemical staining of endometrial specimen showed presence of one or more plasma cells per 10HPF which confirmed chronic endometritis, according to published criteria.
2. women who were pre-menopausal.
3. no evidence of endometrial hyperplasia or malignancy or structural uterine pathology.
4. agreement to have a second endometrial biopsy \~4 weeks after the initial endometrial biopsy.
5. written informed consent obtained

Exclusion Criteria:

1. women who received steroid hormone therapy within one month of recruitment.
2. allergy or suspected allergy to the chosen antibiotic therapy.
3. women who developed any concurrent infection and received any antibiotic therapy during the period of study other than the one prescribed according to the study protocol.

Primary outcomes:
measure: The Conversion Rate of CE (From Positive to Negative)
timeFrame: 1-6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: FuXing Hospital,Capital Medical University
state: Beijing
Study officials:
affiliation: FuXing Hospital,Capital Medical University
name: Dongmei Song, Master
role: PRINCIPAL_INVESTIGATOR
affiliation: FuXing Hospital,Capital Medical University
name: Enlan Xia, Master
role: STUDY_DIRECTOR
affiliation: FuXing Hospital,Capital Medical University
name: Tinchiu Li, PhD
role: STUDY_CHAIR
affiliation: Capital Medical University
name: Xiaoxia Peng, PhD
role: STUDY_DIRECTOR
References:
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citation: Cicinelli E, Matteo M, Tinelli R, Lepera A, Alfonso R, Indraccolo U, Marrocchella S, Greco P, Resta L. Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy. Hum Reprod. 2015 Feb;30(2):323-30. doi: 10.1093/humrep/deu292. Epub 2014 Nov 10.
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citation: Song D, He Y, Wang Y, Liu Z, Xia E, Huang X, Xiao Y, Li TC. Impact of antibiotic therapy on the rate of negative test results for chronic endometritis: a prospective randomized control trial. Fertil Steril. 2021 Jun;115(6):1549-1556. doi: 10.1016/j.fertnstert.2020.12.019. Epub 2021 Feb 3.