RCT(Randomized Clinical Trial ) of Antibiotic Therapy in Chronic Endometritis
Primary Purpose
Chronic Endometritis
Status
Completed
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Antibiotics
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Endometritis focused on measuring chronic endometritis, CD138, antibiotic, conversion rate.
Eligibility Criteria
Inclusion Criteria:
- CD138 immunohistochemical staining of endometrial specimen showed presence of one or more plasma cells per 10HPF which confirmed chronic endometritis, according to published criteria.
- women who were pre-menopausal.
- no evidence of endometrial hyperplasia or malignancy or structural uterine pathology.
- agreement to have a second endometrial biopsy ~4 weeks after the initial endometrial biopsy.
- written informed consent obtained
Exclusion Criteria:
- women who received steroid hormone therapy within one month of recruitment.
- allergy or suspected allergy to the chosen antibiotic therapy.
- 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.
Sites / Locations
- FuXing Hospital,Capital Medical University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Antibiotic group
Control group
Arm Description
This group received antibiotic therapy
This group did not receive antibiotic therapy
Outcomes
Primary Outcome Measures
The Conversion Rate of CE (From Positive to Negative)
Subjects in antibiotic group underwent a second-look hysteroscopy and repeat endometrial biopsy for histopathological CD138 immunohistochemical examination 2-4 weeks after completion of antibiotic treatment and in the follicular phase of the following menstrual cycle. Subjects in control group underwent a second-look hysteroscopy and repeat endometrial biopsy for histopathological CD138 immunohistochemical examination ~4 weeks after recruitment in the follicular phase of the following menstrual cycle.
The biopsies were graded as "negative" for CE if there was less than one plasma cell identified per 10 high-power fields (HPFs) and "positive" when there was one or more plasma cell identified per 10 HPFs.
To compare the cure rate (From positive to negative) of CE in women who received antibiotic therapy (treatment group) with the spontaneous cure rate in those who did not receive antibiotic therapy (control group),
Secondary Outcome Measures
Full Information
NCT ID
NCT02648698
First Posted
December 23, 2015
Last Updated
February 3, 2022
Sponsor
Fu Xing Hospital, Capital Medical University
1. Study Identification
Unique Protocol Identification Number
NCT02648698
Brief Title
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
2. Study Status
Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
January 10, 2016 (Actual)
Primary Completion Date
December 15, 2018 (Actual)
Study Completion Date
December 15, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fu Xing Hospital, Capital Medical University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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:
CD138 immunohistochemical staining of endometrial specimen showed presence of one or more plasma cells per 10HPF which confirmed chronic endometritis, according to published criteria.
women who were pre-menopausal.
no evidence of endometrial hyperplasia or malignancy or structural uterine pathology.
agreement to have a second endometrial biopsy ~4 weeks after the initial endometrial biopsy.
written informed consent obtained
Exclusion Criteria:
women who received steroid hormone therapy within one month of recruitment.
allergy or suspected allergy to the chosen antibiotic therapy.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Endometritis
Keywords
chronic endometritis, CD138, antibiotic, conversion rate.
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
120 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Antibiotic group
Arm Type
Experimental
Arm Description
This group received antibiotic therapy
Arm Title
Control group
Arm Type
No Intervention
Arm Description
This group did not receive antibiotic therapy
Intervention Type
Drug
Intervention Name(s)
Antibiotics
Other Intervention Name(s)
Levofloxacin and Tinidazole
Intervention Description
Levofloxacin Tab and Tinidazole Tab are combined in the antibiotic group
Primary Outcome Measure Information:
Title
The Conversion Rate of CE (From Positive to Negative)
Description
Subjects in antibiotic group underwent a second-look hysteroscopy and repeat endometrial biopsy for histopathological CD138 immunohistochemical examination 2-4 weeks after completion of antibiotic treatment and in the follicular phase of the following menstrual cycle. Subjects in control group underwent a second-look hysteroscopy and repeat endometrial biopsy for histopathological CD138 immunohistochemical examination ~4 weeks after recruitment in the follicular phase of the following menstrual cycle.
The biopsies were graded as "negative" for CE if there was less than one plasma cell identified per 10 high-power fields (HPFs) and "positive" when there was one or more plasma cell identified per 10 HPFs.
To compare the cure rate (From positive to negative) of CE in women who received antibiotic therapy (treatment group) with the spontaneous cure rate in those who did not receive antibiotic therapy (control group),
Time Frame
1-6 months
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
CD138 immunohistochemical staining of endometrial specimen showed presence of one or more plasma cells per 10HPF which confirmed chronic endometritis, according to published criteria.
women who were pre-menopausal.
no evidence of endometrial hyperplasia or malignancy or structural uterine pathology.
agreement to have a second endometrial biopsy ~4 weeks after the initial endometrial biopsy.
written informed consent obtained
Exclusion Criteria:
women who received steroid hormone therapy within one month of recruitment.
allergy or suspected allergy to the chosen antibiotic therapy.
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dongmei Song, Master
Organizational Affiliation
FuXing Hospital,Capital Medical University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Enlan Xia, Master
Organizational Affiliation
FuXing Hospital,Capital Medical University
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Tinchiu Li, PhD
Organizational Affiliation
FuXing Hospital,Capital Medical University
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Xiaoxia Peng, PhD
Organizational Affiliation
Capital Medical University
Official's Role
Study Director
Facility Information:
Facility Name
FuXing Hospital,Capital Medical University
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100038
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
24462055
Citation
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.
Results Reference
background
PubMed Identifier
24177713
Citation
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.
Results Reference
background
PubMed Identifier
21030015
Citation
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.
Results Reference
background
PubMed Identifier
15335255
Citation
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.
Results Reference
background
PubMed Identifier
23440678
Citation
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.
Results Reference
background
PubMed Identifier
21749546
Citation
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.
Results Reference
background
PubMed Identifier
25385744
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.
Results Reference
background
PubMed Identifier
26207958
Citation
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.
Results Reference
result
PubMed Identifier
33549312
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.
Results Reference
derived
Links:
URL
http://www.ncbi.nlm.nih.gov/pubmed/26207958
Description
2015
URL
http://www.ncbi.nlm.nih.gov/pubmed/24462055
Description
2014
URL
http://www.ncbi.nlm.nih.gov/pubmed/24177713
Description
2013 Oct 31
URL
http://www.ncbi.nlm.nih.gov/pubmed/21030015
Description
2011 Mar
URL
http://www.ncbi.nlm.nih.gov/pubmed/?term=Routine+syndecan-1+immunohistochemistry+aids+in+the+diagnosis+of+chronic+endometritis
Description
2004 Sep
URL
http://www.ncbi.nlm.nih.gov/pubmed/23440678
Description
2012 Jul
URL
http://www.ncbi.nlm.nih.gov/pubmed/?term=Immunohistochemistrical+and+clinicopathological+characterization+of+chronic+endometritis
Description
2011 Jul 12
URL
http://www.ncbi.nlm.nih.gov/pubmed/25385744
Description
2015 Feb
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RCT(Randomized Clinical Trial ) of Antibiotic Therapy in Chronic Endometritis
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