Εffectiveness of Intrauterine Antibiotic Administration for Treatment of Chronic Endometritis

Investigating the Effectiveness of Innovative Intrauterine Antibiotic Therapy for the Treatment of Patients With Chronic Endometritis

Chronic Endometritis (CE) is related to infertility and entails a challenging management. This study investigates the treatment of off-label intrauterine antibiotic infusion either separately or combined with oral antibiotic administration, and it assesses respective performance against the gold standard treatment of oral antibiotic adminstration. Data sourced herein reports on treatment efficiency, defined as a negative diagnosis for chronic endometritis.

Study Overview

• Status: Recruiting
• Conditions: Chronic Endometritis
• Intervention / Treatment: Drug: Intrauterine infusion; Drug: Oral administration

Detailed Description

An infectious endometrial environment caused by certain pathologies could compromise establishment of the initial interaction between the embryo and the endometrium. Chronic endometritis (CE) is a case of a persistent endometrial inflammation caused by infectious agents namely Escherichia Coli, Enterococcus faecalis, Streptococcus agalactiae, Mycoplasma, Ureaplasma, and Chlamydia. The perplexity of managing CE is attributed to its asymptomatic nature rendering a definitive diagnosis rather challenging. The list of potential symptoms is limited and vague while manifestation of the disease may be mild and may not correspond to severity. Symptoms include pain in the pelvic cavity, dispareunia, uterine bleeding, vaginal infections and cystitis, and mild gastro-intestinal discomfort. CE is described as a chronic disorder due to its long duration and persistent nature, with potentially slow progression and complex causality, severely compromising reproductive potential of patients.

The antibiotic treatments are primarily administered orally and endometrial re-examination is performed following treatment. It should be emphasized that apart from the differences in the types of antibiotics included, there are also significant discrepancies regarding the dosage of each antibiotic and the different schemes suggested by each practice. Following the antibiotic regime, endometrial receptivity is anticipated to improve. However, a significant correlation between the antibiotic therapeutic approach and a positive results in IVF has failed to be established in literature, indicating that oral antibiotic administration is unseccessful in improving IVF outcome.

A pilot study published by the investigators indicated that combination of intrauterine infusion of antibiotics and oral administration can be more effective in treating CE than solely oral administration. However, it has not been evaluated if sole intrauterine infusion of antibiotics can be of similar effectiveness when compared to the combined regime including intrauterine infusion and oral andministration, or when compared to the gold standard treatment including only oral administration of antibiotics.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Konstantinos Sfakianoudis, MD; Phone Number: 2106894326; Email: sfakianosc@yahoo.gr

Study Locations

• Greece
  • Athens, Greece, 15232
    • Recruiting
    • Genesis AC
    • Contact: Panagiotis Tzonis, MD; Phone Number: 6937115569; Email: ptzonis@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Positive diagnosis of CE following hysteroscopy and endometrial biopsy (positive diagnosis is required by both evaluations)
• Signed Informed Consent
• 18.5 < BMI < 30

Exclusion Criteria:

• Diagnosed endometriosis or other related Pelvic Inflammatory Disorder (PID)
• Current or previous cancer diagnosis
• Auto-immune or genetic disorders
• Menstrual cycle disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intrauterine infusion of antibiotics; Thirty women will receive only intrauterine infusion of antibiotics for 30 days.	Drug: Intrauterine infusion; A total of 10 intrauterine infusions of 3ml of ciprofloxacin at a concentration of 200 mg/100 ml
Experimental: Combination of intrauterine infusion and oral administration of antibiotics; Thirty women will receive a combination of intrauterine infusion and oral administration of antibiotics for 30 days.	Drug: Intrauterine infusion; A total of 10 intrauterine infusions of 3ml of ciprofloxacin at a concentration of 200 mg/100 ml; Drug: Oral administration; per os antibiotic administration as the standard line of strategy for treating CE of doxycycline at a dosage of 100mg twice a day and metronidazole of 500mg twice a day for a total of 30 days
Active Comparator: Oral administration of antibiotics; Thirty women will receive only oral administration of antibiotics for 30 days.	Drug: Oral administration; per os antibiotic administration as the standard line of strategy for treating CE of doxycycline at a dosage of 100mg twice a day and metronidazole of 500mg twice a day for a total of 30 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Negative diagnosis of CE following hysteroscopy and endometrial biopsy	All participants will be subjected to hysteroscopy and endometrial biopsy following completion of treatment. Regarding hysteroscopy the presence of endometritis will be evaluated according to the published unified diagnostic criteria for CE. The endometrial biopsy will be performed employing a pipelle. To minimize contamination risk, following the placement of a vaginal speculum and cleaning external uterine ostium with an iodine solution, the pipelle will be inserted under visual control into the uterine cavity ensuring avoidance of any contact with vaginal walls. Endometrial samples will be diluted into 2 ml of saline for histological analysis. For histological analysis the endometrium samples will be fixated employing neutral formalin and paraffin. To stain the microsections, hematoxyline and eosin will be engaged. CD138 staining will be performed and positivity will indicate a CE diagnosis (>1 plasma cell per 10HPFs). A negative CE diagnosis should be confirmed by both assessments	Negative diagnosis of CE will be assessed in one month -immidiately after treatment completion-.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v6.0	Number of reports of side-effects according to CTCAE v6.0 per treated patients	Side-effects will be monitored for one month from treatment initiation which is until completion of treatment

Collaborators and Investigators

• Sponsor: Genesis Athens Clinic
• Collaborators: National and Kapodistrian University of Athens
• Investigators: Principal Investigator: Konstantinos Sfakianoudis, MD, Genesis Athens Clinic

Publications and helpful links

General Publications

• Pantos K, Simopoulou M, Maziotis E, Rapani A, Grigoriadis S, Tsioulou P, Giannelou P, Nitsos N, Tzonis P, Koutsilieris M, Sfakianoudis K. Introducing intrauterine antibiotic infusion as a novel approach in effectively treating chronic endometritis and restoring reproductive dynamics: a randomized pilot study. Sci Rep. 2021 Aug 2;11(1):15581. doi: 10.1038/s41598-021-95072-w.

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2021
• Primary Completion (Anticipated): January 30, 2024
• Study Completion (Anticipated): April 30, 2024

Study Registration Dates

• First Submitted: December 23, 2021
• First Submitted That Met QC Criteria: January 12, 2022
• First Posted (Actual): January 25, 2022

Study Record Updates

• Last Update Posted (Actual): February 24, 2023
• Last Update Submitted That Met QC Criteria: February 22, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Uterine Diseases; Adnexal Diseases; Pelvic Inflammatory Disease; Endometritis
• Other Study ID Numbers: IAI-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No