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

Chronic Endometritis Clinical Trial

Official title:

A Prospective, Randomized,Controlled Trial on the Effect of Antibiotic Therapy on Endometrial Response in Women With Chronic Endometritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02648698
• Other study ID #: FuXingH
• Status: Completed
• Phase: N/A
• Start date: January 10, 2016
• Est. completion date: December 15, 2018

Study information

• Verified date: February 2022
• Source: Fu Xing Hospital, Capital Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: December 15, 2018
• Est. primary completion date: December 15, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Endometritis
• Endometritis

Intervention

Drug:
• Antibiotics
Levofloxacin Tab and Tinidazole Tab are combined in the antibiotic group

Locations

Country	Name	City	State
China	FuXing Hospital,Capital Medical University	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Fu Xing Hospital, Capital Medical University

Country where clinical trial is conducted

China, 

References & Publications (8)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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),	1-6 months

External Links

•   2004 Sep
•   2011 Jul 12
•   2011 Mar
•   2012 Jul
•   2013 Oct 31
•   2014
•   2015
•   2015 Feb