Empiric Therapy of Mucopurulent Cervicitis (MPC)

Study Overview
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Brief Summary
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Mucopurulent cervicitis (MPC) is a syndrome with associated symptoms including mucopurulent discharge (mucus and pus) from the cervix and other signs of inflammation such as easily induced cervical bleeding. The purpose of this study is to evaluate the effectiveness of no treatment versus empiric treatment with a single dose of cefixime and azithromycin for cure of MPC. Empiric treatment is the initiation of treatment prior to a firm diagnosis. Study participants will include 772 women ages 18 and older in good health with MPC. Women will be randomly assigned to 1 of 2 possible study groups: Group 1 will receive a single dose of cefixime and azithromycin antibiotics and Group 2 will receive placebo (inactive substance). Study procedures will include pelvic examination with a cervical swab sample. Participants will be involved in study related procedures for approximately 2 months, which includes 3 study visits.

Detailed Description
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Mucopurulent cervicitis (MPC) is a clinical syndrome characterized by the presence of mucopurulent discharge from the cervix and other signs of inflammation such as easily induced cervical bleeding. This phase III study is designed to evaluate the effectiveness of no treatment (placebo) versus empiric treatment with a single dose of cefixime 400 mg and azithromycin 1 gram for clinical cure of MPC at 2 months of follow-up. Secondary aims of the study are: to compare the pelvic inflammatory disease (PID) rate and adverse event rates between no treatment (placebo) versus empiric treatment; explore the role of bacterial vaginosis and Mycoplasma genitalium in the persistence of MPC; evaluate microbiological cure rate of M. genitalium in women treated with cefixime and azithromycin versus placebo; and present the clinical cure, partial response and failure proportions at 2-3 weeks and 2 months for each study arm. Participants will include 772 women greater than or equal to 18 years of age from Sexually Transmitted Disease (STD) or Family Planning (FP) clinics in good general health with MPC in New Orleans, LA; Birmingham, AL; Jackson, MS; Los Angeles, CA; and an additional site to be determined. Research specimens will be obtained at the time of the pelvic examination. As part of the study protocol, 3 cervical and 4 vaginal swabs will be collected at screening, follow-up visit 1, and follow-up visit 2. Eligible participants with clinical MPC at the time of their pelvic examination (cervical mucopus or easily induced cervical bleeding), will be consented, screened, enrolled, and randomized to one of the following arms: Group 1: empiric treatment: a single dose of cefixime 400 mg (1 capsule oral at 400 mg) and azithromycin 1 gm (2 capsules oral at 500 mg each) or Group 2: no treatment: placebo pills that look identical to the above medications. Subjects will be involved in study related procedures for 2 months.

Official Title
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A Randomized Trial to Evaluate the Need for Empiric Therapy for Mucopurulent Cervicitis of Unknown Etiology

Conditions
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Vaginitis Bacterial, Cervicitis

Intervention / Treatment
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* Other: Placebo
* Drug: Azithromycin
* Drug: Cefixime


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women greater than or equal to 18 years old in Sexually Transmitted Disease (STD) clinics or Family Planning clinics. Presence of cervical mucopus and/or easily induced cervical bleeding on pelvic exam via endocervical swab. Greater than or equal to 30 white blood cells (WBCs) per high power field in the cervical Gram stain. (Note: the cervical Gram stains will be sent to a central lab for review. The results will not be available at the time of enrollment. Subjects who do not meet this criterion will be withdrawn from the study at the time the results are available). Willingness to provide written informed consent Willing to abstain from sexual intercourse or use condoms during the entire study (approximately 2 months). Willing to abstain from using vaginal products during the entire study (approximately 2 months). Exclusion Criteria: Signs and symptoms of pelvic inflammatory disease, including cervical motion, uterine, or adnexal tenderness. History of pelvic inflammatory disease (PID), ectopic pregnancy or recurrent cervicitis (3 or more episodes in the prior year) or written documentation of recent cervicitis (within past 30 days). Gonorrhea or Chlamydia on nucleic acid amplification test (NAAT) at time of enrollment. (Participant testing positive for Neisseria gonorrhoeae (GC) or Chlamydia trachomatis (CT) on enrollment visit sample will be discontinued). Women with motile trichomonas on wet mount examination or positive trichomonas culture at time of enrollment. Women with symptomatic bacterial vaginosis (BV) (based on clinical Amsel criteria for BV and reported symptoms by participant, i.e. discharge, vaginal odor, etc). Use of vaginal products in past 48 hours (i.e. douching, use of vaginal medications or suppositories). History of chronic renal disease by verbal or documented history. Current use of probenecid. Nursing mothers. Colitis or coagulopathy as per patient self-report. Known allergy to cephalosporins, penicillin or macrolides by verbal or documented history. History of latex allergy. Use of systemic antibiotics (oral or intravenous), vaginal antibiotics, vaginal antifungal, or oral antifungal use within 30 days of study enrollment. Women who will require antibiotic treatment due to GC or CT in a sexual partner. Serious underlying conditions, including human immunodeficiency virus (HIV) or other primary or secondary immunosuppressive condition. Concomitant infection, which requires antimicrobial therapy (for example, urinary tract infection, sinusitis, skin and soft tissue infection, tooth abscess, etc.) or expected use of any antibiotic/antimicrobial therapy during the study. Menstruation at the time of screening visit. Women who are menstruating can be screened after cessation of bleeding. Active herpes outbreak at the time of enrollment determined by clinical observation. Suspected pregnancy or positive urine pregnancy test at screening or actively seeking pregnancy during study period. Any clinical adverse event, intercurrent illness, or other medical condition or situation as determined by the investigator that is present or occurs such that participation in the study would not be in the best interest of the participant. Previously enrolled in this study. Unable to follow the protocol (inc. inability to comply with the follow-up procedures). Failing to provide contact information.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo. | Other: Placebo<br>* Capsule will be filled with lactose and be identical in appearance to the capsule with the active ingredient.<br>|
| Experimental: Azithromycin/Cefixime<br>A single dose of cefixime 400 mg (1 tablet oral at 400 mg) and azithromycin 1 gram (2 tablets oral at 500 mg each). | Drug: Azithromycin<br>* Single dose will consist of 2 over-encapsulated capsules (500 mg each) administered orally.<br>Drug: Cefixime<br>* Single dose will consist of 1 over-encapsulated capsule (400 mg) administered orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate Clinical Cure in Participants Not Treated Versus Participants Empirically Treated With Cefixime and Azithromycin for Mucopurulent Cervicitis (MPC). | The proportion of participants who have cleared MPC by the second follow-up visit. Clinical cure is defined as: absence of cervical mucopus and absence of easily induced cervical bleeding and < 30 white blood cells per oil immersion field on cervical gram stain. | Visit 2 - 2 months (Day 50-70). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine Pelvic Inflammatory Disease (PID) in Patients Empirically Treated With Cefixime and Azithromycin for Mucopurulent Cervicitis (MPC) in Comparison to no Treatment. | The number of participants experiencing PID after randomization. | At 2-3 week and 2 month (Day 50-70) follow-up. | 
| Examine Adverse Events in Patients Empirically Treated With Cefixime and Azithromycin for Mucopurulent Cervicitis (MPC) in Comparison to no Treatment. | The proportion of participants experiencing one or more adverse events after randomization. | At 2-3 week and 2 month (Day 50-70) follow-up. | 
| Explore the Role of Bacterial Vaginosis (BV) in Persistent Mucopurulent Cervicitis (MPC). | Proportion of participants with clinical failure, partial response, or clinical cure for mucopurulent cervicitis at 2 month follow-up according to asymptomatic bacterial vaginosis status at 2 month follow-up. Clinical Failure: Persistent cervical mucopus and/or easily induced cervical bleeding, and the presence of > 30 WBCs per oil immersion field on cervical gram stain OR Signs of pelvic inflammatory disease, including cervical motion tenderness, uterine tenderness or adnexal tenderness. Partial Response: Persistent cervical mucopus and/or easily induced cervical bleeding and <30 WBCs per oil immersion field on cervical gram stain OR The presence of ≥ 30 WBCs per oil immersion field on cervical gram stain in the absence of both cervical mucopus and easily induced cervical bleeding. Clinical Cure: • Absence of cervical mucopus and absence of easily induced cervical bleeding and < 30 WBC's per oil immersion field on cervical gram stain. | At 2 month (Day 50-70) follow-up. | 
| Explore the Role of Mycoplasma Genitalium in Persistent Mucopurulent Cervicitis (MPC). | Proportion of participants with clinical failure, partial response, or clinical cure for mucopurulent cervicitis at 2 months according to mycoplasma genitalium status(positive cervical or vaginal swabs versus both negative) at 2 months. Clinical Failure: Persistent cervical mucopus and/or easily induced cervical bleeding, and the presence of > 30 WBCs per oil immersion field on cervical gram stain OR Signs of pelvic inflammatory disease, including cervical motion tenderness, uterine tenderness or adnexal tenderness. Partial Response: Persistent cervical mucopus and/or easily induced cervical bleeding and <30 WBCs per oil immersion field on cervical gram stain OR The presence of ≥ 30 WBCs per oil immersion field on cervical gram stain in the absence of both cervical mucopus and easily induced cervical bleeding. Clinical Cure: • Absence of cervical mucopus and absence of easily induced cervical bleeding and < 30 WBC's per oil immersion field on cervical gram stain. | At 2 month (Day 50-70) follow-up. | 
| Evaluate Microbiological Cure of Mycoplasma Genitalium in Women Treated With Cefixime and Azithromycin Versus Placebo. | The proportion of participants with mycoplasma genitalium at baseline who clear mycoplasma genitalium in either the vagina or cervix at their last follow-up visit. | At 2-3 weeks and 2 month (Day 50-70) follow-up. | 
| Determine the Clinical Cure, Partial Response and Failure Proportions for Mucopurulent Cervicitis at 2 Months for Each Study Arm. | Clinical Failure: Persistent cervical mucopus and/or easily induced cervical bleeding, and the presence of > 30 WBCs per oil immersion field on cervical gram stain OR Signs of pelvic inflammatory disease, including cervical motion tenderness, uterine tenderness or adnexal tenderness. Partial Response: Persistent cervical mucopus and/or easily induced cervical bleeding and <30 WBCs per oil immersion field on cervical gram stain OR The presence of ≥ 30 WBCs per oil immersion field on cervical gram stain in the absence of both cervical mucopus and easily induced cervical bleeding. Clinical Cure: • Absence of cervical mucopus and absence of easily induced cervical bleeding and < 30 WBC's per oil immersion field on cervical gram stain. | At 2 month ( Day 50-70) follow-up. | 
| Determine the Clinical Cure, Partial Response and Failure Proportions for Mucopurulent Cervicitis at 2-3 Weeks for Each Study Arm. | Clinical Failure: Persistent cervical mucopus and/or easily induced cervical bleeding, and the presence of > 30 WBCs per oil immersion field on cervical gram stain OR Signs of pelvic inflammatory disease, including cervical motion tenderness, uterine tenderness or adnexal tenderness. Partial Response: Persistent cervical mucopus and/or easily induced cervical bleeding and <30 WBCs per oil immersion field on cervical gram stain OR The presence of ≥ 30 WBCs per oil immersion field on cervical gram stain in the absence of both cervical mucopus and easily induced cervical bleeding. Clinical Cure: • Absence of cervical mucopus and absence of easily induced cervical bleeding and < 30 WBC's per oil immersion field on cervical gram stain. | At 2-3 weeks follow-up. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mucopurulent cervicitis, chlamydia, gonorrhea, women