RCT(Randomized Clinical Trial ) of Antibiotic Therapy in Chronic Endometritis

NCT ID: NCT02648698

Last Updated: 2022-02-07

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-01-10

Study Completion Date

2018-12-15

Brief Summary

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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

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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.

Conditions

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Chronic Endometritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Investigators

Study Groups

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Antibiotic group

This group received antibiotic therapy

Group Type EXPERIMENTAL

Antibiotics

Intervention Type DRUG

Levofloxacin Tab and Tinidazole Tab are combined in the antibiotic group

Control group

This group did not receive antibiotic therapy

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Antibiotics

Levofloxacin Tab and Tinidazole Tab are combined in the antibiotic group

Intervention Type DRUG

Other Intervention Names

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Levofloxacin and Tinidazole

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Fu Xing Hospital, Capital Medical University

OTHER

Sponsor Role lead

Responsible Party

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Song Dongmei

Hysteroscopy Center

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Dongmei Song, Master

Role: PRINCIPAL_INVESTIGATOR

FuXing Hospital,Capital Medical University

Enlan Xia, Master

Role: STUDY_DIRECTOR

FuXing Hospital,Capital Medical University

Tinchiu Li, PhD

Role: STUDY_CHAIR

FuXing Hospital,Capital Medical University

Xiaoxia Peng, PhD

Role: STUDY_DIRECTOR

Capital Medical University

Locations

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FuXing Hospital,Capital Medical University

Beijing, Beijing Municipality, China

Site Status

Countries

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China

References

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McQueen DB, Bernardi LA, Stephenson MD. Chronic endometritis in women with recurrent early pregnancy loss and/or fetal demise. Fertil Steril. 2014 Apr;101(4):1026-30. doi: 10.1016/j.fertnstert.2013.12.031. Epub 2014 Jan 23.

Reference Type BACKGROUND
PMID: 24462055 (View on PubMed)

Cicinelli E, Matteo M, Tinelli R, Pinto V, Marinaccio M, Indraccolo U, De Ziegler D, Resta L. Chronic endometritis due to common bacteria is prevalent in women with recurrent miscarriage as confirmed by improved pregnancy outcome after antibiotic treatment. Reprod Sci. 2014 May;21(5):640-7. doi: 10.1177/1933719113508817. Epub 2013 Oct 31.

Reference Type BACKGROUND
PMID: 24177713 (View on PubMed)

Kitaya K. Prevalence of chronic endometritis in recurrent miscarriages. Fertil Steril. 2011 Mar 1;95(3):1156-8. doi: 10.1016/j.fertnstert.2010.09.061. Epub 2010 Oct 28.

Reference Type BACKGROUND
PMID: 21030015 (View on PubMed)

Bayer-Garner IB, Nickell JA, Korourian S. Routine syndecan-1 immunohistochemistry aids in the diagnosis of chronic endometritis. Arch Pathol Lab Med. 2004 Sep;128(9):1000-3. doi: 10.5858/2004-128-1000-RSIAIT.

Reference Type BACKGROUND
PMID: 15335255 (View on PubMed)

Kannar V, Lingaiah HK, Sunita V. Evaluation of endometrium for chronic endometritis by using syndecan-1 in abnormal uterine bleeding. J Lab Physicians. 2012 Jul;4(2):69-73. doi: 10.4103/0974-2727.105584.

Reference Type BACKGROUND
PMID: 23440678 (View on PubMed)

Kitaya K, Yasuo T. Immunohistochemistrical and clinicopathological characterization of chronic endometritis. Am J Reprod Immunol. 2011 Nov;66(5):410-5. doi: 10.1111/j.1600-0897.2011.01051.x. Epub 2011 Jul 12.

Reference Type BACKGROUND
PMID: 21749546 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25385744 (View on PubMed)

McQueen DB, Perfetto CO, Hazard FK, Lathi RB. Pregnancy outcomes in women with chronic endometritis and recurrent pregnancy loss. Fertil Steril. 2015 Oct;104(4):927-931. doi: 10.1016/j.fertnstert.2015.06.044. Epub 2015 Jul 21.

Reference Type RESULT
PMID: 26207958 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33549312 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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FuXingH

Identifier Type: -

Identifier Source: org_study_id

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