Clinical trial NCT06650540: Levofloxacin Plus Metronidazole Suppositories Versus Levofloxacin Co-administered with Metronidazole Tablets in Chronic Endometritis
Official title: Levofloxacin Plus Metronidazole Suppositories Versus Levofloxacin Co-administered with Metronidazole Tablets for the Treatment of Chronic Endometritis: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: IVF
Keywords: Chronic Endometritis
pregnancy outcomes
pharmacological treatment
Lead sponsor: Peking University Third Hospital
Sponsor class: OTHER
First posted: 2024-10-21
Enrollment: 800
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a single randomised controlled trial. The investigators plan to randomise 800 participants to the levofloxacin plus metronidazole suppositories versus levofloxacin co-administered with metronidazole tablets for the treatment of chronic endometritis in a 1:1 rate. Primary outcome will be the live birth rate after the embryo transfer.

Detailed description: Chronic endometritis (CE) is a pathological condition characterized by inflammation and destruction of the endometrium. In this disease state, microorganisms coexist with the host's immune system in a balanced manner. However, for the majority of patients with CE, clinical symptoms are nonspecific and atypical, rendering diagnosis based on clinical signs or blood tests unreliable. Consequently, invasive procedures such as histopathological examination of the endometrium or hysteroscopy are often necessary to establish a definitive diagnosis. The infiltration of plasma cells in the endometrial stroma associated with CE, together with increased production of immunoglobulins and pro-inflammatory cytokines, can reduce endometrial receptivity. This reduction in receptivity can lead to an increased risk of female infertility, lower pregnancy rates, and reduced live birth rates, which are linked to unexplained infertility, repeated failure of embryo implantation, and recurrent miscarriages. While the etiology of CE remains elusive, it is widely believed to be related to infection by pathogenic microorganisms such as Streptococcus, Enterococcus faecalis, Escherichia coli, Staphylococcus , Klebsiella pneumoniae, Ureaplasma, and Mycoplasma, which can ascend from the vagina into the uterine cavity. Preliminary basic research by investigators also supports the notion that bacterial infections are a leading cause of endometritis. The mainstay of CE treatment currently involves oral antibiotics, with a common regimen being colabitux (500 mg once daily for 14 days) in combination with metronidazole (400 mg twice daily for 14 days). However, oral antibiotics can face issues such as drug resistance, suboptimal local concentrations of the drug, and a propensity to cause gastrointestinal side effects like nausea, vomiting, diarrhea, abdominal distension, and dermatological reactions like skin rashes and leukopenia, which can lead to treatment interruptions and reduced efficacy in managing chronic endometritis. Therefore, there is a need to explore methods to enhance the treatment success rate of CE. Metronidazole suppositories, composed primarily of metronidazole, are used vaginally to treat bacterial infections and other types of bacterial-induced vaginitis. Acting directly on the local area, these suppositories typically exhibit faster and more pronounced therapeutic effects without adversely affecting other tissues and organs. Given that the vagina is connected to the uterine cavity via the cervix, investigators hypothesized that local vaginal administration of the medication might be more effective. This approach not only achieves higher local concentrations of the drug in the uterine cavity, but also prevents ascending infection of vaginal bacteria.

In the prospective, randomized study conducted by investigators, the efficacy of levofloxacin plus metronidazole suppository versus levofloxacin co-administered with metronidazole tablets was compared in patients with chronic endometritis. By comparing the pregnancy outcomes of the two groups, the aim was to identify a superior treatment strategy, enhance treatment efficacy, and improve clinical outcomes.

Purpose The objective of this study is to investigate the efficacy of metronidazole therapy in enhancing treatment outcomes for chronic endometritis, with the aim of increasing clinical pregnancy and live birth rates in IVF procedures, reducing miscarriage rates, and thereby offering a safer and more effective treatment option for participants with chronic endometritis who are considering pregnancy.

Design This study is designed as a randomized controlled trial. Study Population

Inclusion Criteria:

1. Infertile participants between the ages of 20 and 42.
2. Participants who have undergone hysteroscopy and endometrial biopsy, resulting in a pathological diagnosis of chronic endometritis.
3. Participants with a blood FSH level of 12 U/L on the second day of their menstrual cycle.
4. Participants who have provided informed consent and signed the consent form.

Exclusion Criteria:

1. Participants diagnosed with uterine submucosal fibroids, a history of uterine malformations or previous corrective surgeries for such deformities, uterine intrauterine adhesions, or a history of pelvic tuberculosis or endometrial tuberculosis, including cases with pathology suggesting endometrial tuberculosis.
2. Participants or their partners with a history of fetal or child chromosomal abnormalities and those planning a pre-implantation genetic screening.
3. Participants with a well-documented clear history of allergy to the study medication.

Eligibility criteria: Inclusion Criteria:

* Infertile patients aged 20-42 years
* Hysteroscopy and endometrial biopsy were performed, and the
* Pathological diagnosis was chronic endometritis
* Serum FSH level on the second day of menstruation was ≤12U/L
* Agree and sign the informed consent form

Exclusion Criteria:

* Patients with the following diagnoses: submucosal myoma; Uterine malformation or previous surgery for correction of uterine deformity; Intrauterine adhesions; The previous history of pelvic tuberculosis or endometrial tuberculosis or the current pathology suggested endometrial tuberculosis; Endometrial hyperplasia or endometrial cancer
* Patients with spouse, previous fetal or child chromosomal abnormalities who plan to undergo preimplantation genetic screening
* Patients with a history of allergy to study drugs

Primary outcomes:
measure: live birth rate after the first embryo transfer
timeFrame: 22 weeks to 43 weeks gestation after the first embryo transfer cycle
Secondary outcomes:
measure: Clinical pregnancy
timeFrame: around 7 weeks' gestation after the first embryo transfer cycle
measure: Ongoing pregnancy
timeFrame: 12 weeks to 43weeks gestation after the first embryo transfer cycle
measure: Biochemical pregnancy
timeFrame: about 14 days after embryo transfer
measure: Miscarriage
timeFrame: 6-22 weeks of gestation
measure: Cumulative live birth
timeFrame: 6 monti after the first embryo transfer
measure: Pre-eclampsia
timeFrame: after 20 weeks of gestation
measure: Gestational hypertension
timeFrame: after 20 weeks of gestation
measure: Gestational diabetes mellitus
timeFrame: between 24 -28 weeks of gestation
measure: Premature rupture of membrane(PROM)rate
timeFrame: Time Frame: the day of delivery
measure: Preterm delivery
timeFrame: up to 37 weeks
measure: Placenta previa
timeFrame: the day of delivery
measure: Postpartum hemorrhage
timeFrame: the day of delivery
measure: Birth weight
timeFrame: the day of delivery
measure: Stillbirth
timeFrame: the day of delivery
measure: Mode of delivery
timeFrame: the day of delivery
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking university third hospital
Study officials:
References: