The Importance of Anti-anaerobic Therapy for Acute Pelvic Inflammatory Disease (PID)

Phase 2

Completed

• Conditions: Pelvic Inflammatory Disease
• Interventions: Drug: Ceftriaxone; Drug: Doxycycline; Drug: Placebo Oral Capsule; Drug: Metronidazole

• Registration Number: NCT01160640
• Lead Sponsor: Harold Wiesenfeld

Brief Summary

This study is a randomized placebo-controlled trial comparing two antibiotic treatment regimens for acute PID. Women with acute PID will be randomized to one of two treatment regimens: 1) a single intramuscular dose of ceftriaxone 250 mg, doxycycline 100 mg orally twice a day for 14 days, along with placebo tablets orally twice a day for 14 days or 2) same doses of ceftriaxone and doxycycline, and metronidazole 500 mg orally twice a day for 14 days. The primary objective is to compare the eradication of anaerobic organisms from the upper genital tract between women who receive standard outpatient antibiotic treatment to those who receive standard outpatient treatment along with a two-week course of metronidazole.

Detailed Description

This study is a randomized placebo-controlled trial comparing two antibiotic treatment regimens for acute PID. Women with acute PID will be randomized to one of two treatment regimens. One group of women will receive a single intramuscular dose of ceftriaxone 250 mg, doxycycline 100 mg orally twice a day for 14 days, along with placebo tablets orally twice a day for 14 days. The second group of women will receive the same doses of ceftriaxone and doxycycline, and metronidazole 500 mg orally twice a day for 14 days. The primary objective is to compare the eradication of anaerobic organisms from the upper genital tract in women with acute PID who receive standard outpatient antibiotic treatment to the eradication of these organisms from the upper genital tract in women who receive standard outpatient treatment along with a two-week course of metronidazole. Women will be followed for one month for clinical outcomes, and will undergo assessment for clearance of microorganisms from the upper genital tract. Our hypothesis is that an antibiotic treatment regimen that includes anaerobic coverage will more effectively clear anaerobic organisms from the endometrium in women with acute PID compared to a standard antibiotic treatment regimen lacking effective antibiotic coverage against anaerobes.

Study Timeline

• Study First Submitted: 2010-07-08
• Study First Submitted QC: 2010-07-09
• Study First Posted: 2010-07-12
• Study Start: 2010-11
• Primary Completion: 2015-08
• Study Completion: 2015-08
• Results First Submitted: 2016-10-26
• Results First Submitted QC: 2016-10-26
• Results First Posted: 2016-12-21
• Status Verified: 2018-07
• Last Update Submitted: 2018-07-06
• Last Update Posted: 2018-07-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 233

Inclusion Criteria

Women must meet all of the following inclusion criteria:

1. Age 15-40 at the time of enrollment (Note: Participants between the ages of 15-17 will require written informed consent from parent/legal guardian. Written assent will also be obtained from the minor)

2. Acute PID, defined by symptoms and signs guided by current CDC guidelines:50

   1. Current symptoms of lower abdominal or pelvic pain (present for ≤30 days) AND
   2. Cervical motion tenderness AND/OR uterine tenderness AND/OR adnexal tenderness on pelvic examination

3. Ability to provide written informed consent

Exclusion Criteria

Women with any of the following will be ineligible to participate:

1. Pregnant or nursing a baby (Note: a urine pregnancy test will be done at enrollment. Result must be negative to participate in the study.)

2. Uterine procedure (e.g. dilation and curettage, abortion) or miscarriage within the past 6 weeks.

3. Allergy to any of the study medications (cephalosporins, doxycycline, or metronidazole) or Type 1 hypersensitivity allergic reaction to penicillin for those with unknown tolerance to cephalosporins.

4. Systemic or vaginal antibiotic therapy in the preceding 7 days

5. Requires inpatient PID therapy (per the current CDC guidelines)50

6. Inability to obtain an endometrial biopsy at enrollment

7. Known inability to comply with the follow-up visits

8. Prior hysterectomy

9. Menopause (including natural menopause defined as lack of menses for 12 consecutive months [in the absence of pregnancy] and surgical menopause defined as a woman who has had both ovaries removed)

10. Inability to swallow pills

11. Not willing to refrain from alcohol during the two week treatment period (and two additional days following completion of study medication)

12. Other condition present at enrollment that requires additional antibiotic treatment

13. Current use of any of the following medications:

    • Anticoagulants, coumarin- or indandione-derivative: warfarin
    • cimetidine (Tagamet)
    • Disulfiram
    • Seizure medications including: phenytoin (Dilantin), carbamezapine (Tegretol), barbiturates (i.e. Phenobarbital)
    • Lithium
    • Immunosuppressive drugs including: cyclosporine, amprenavir
    • Antacids, minerals or bismuth subsalicylate (Pepto Bismol)

14. Any condition, in the opinion of the investigator that would interfere with the participant's safety or with study outcomes

15. Participation in any study involving an investigational product in the past 30 days or anticipation of participation in any study using an investigational product in the next 30 days

16. Previous participation in this study

17. Evidence of a tuboovarian abscess

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ceftriaxone/Doxycycline/Placebo Oral Cap	Ceftriaxone	ceftrixone 250mg IM single dose plus doxycycline 100 mg PO bid x 14 days plus placebo oral capsule PO bid x 14 days
Ceftriaxone/Doxycycline/Placebo Oral Cap	Doxycycline	ceftrixone 250mg IM single dose plus doxycycline 100 mg PO bid x 14 days plus placebo oral capsule PO bid x 14 days
Ceftriaxone/Doxycycline/Placebo Oral Cap	Placebo Oral Capsule	ceftrixone 250mg IM single dose plus doxycycline 100 mg PO bid x 14 days plus placebo oral capsule PO bid x 14 days
Ceftriaxone, Doxycycline, Metronidazole	Ceftriaxone	ceftriaxone 250 mg IM single dose plus doxycycline 100 mg PO bid x 14 days plus metronidazole 500 mg PO bid x 14 days
Ceftriaxone, Doxycycline, Metronidazole	Doxycycline	ceftriaxone 250 mg IM single dose plus doxycycline 100 mg PO bid x 14 days plus metronidazole 500 mg PO bid x 14 days
Ceftriaxone, Doxycycline, Metronidazole	Metronidazole	ceftriaxone 250 mg IM single dose plus doxycycline 100 mg PO bid x 14 days plus metronidazole 500 mg PO bid x 14 days

Primary Outcome Measures

Name	Time	Method
Clearance of Anaerobic Organisms From the Endometrium	Enrollment to 30 days	Clearance of anaerobic microorganisms from the endometrium at the 30 day follow-up visit among women who had anaerobic microorganisms detected in their endometrial tissue sample at enrollment. Clearance is defined as no anaerobic microorganisms detected in the endometrial tissue biopsy sample collected at the 30-day visit.

Secondary Outcome Measures

Name	Time	Method
The Prevalence of M. Genitalium in the Cervix and Endometrium From Women With Acute PID.	enrollment	The number of women who had M. genitalium detected in cervical and endometrial biopsy cultures by nucleic acid amplification tests at enrollment.
The Eradication of M. Genitalium From the Lower and Upper Genital Tract Following Antibiotic Therapy for Acute PID.	Enrollment to 30 days	M. genitalium not detected in the cervical and endometrial cultures by nucleic acid amplification testing at the 30 day visit among women who had M. genitalium detected at either anatomical site at the enrollment visit.
Resolution of Clinical Signs and Symptoms of Acute PID - Intention to Treat Analysis	Enrollment to 3 day follow up visit	Clinical response to treatment is improvement (reduction) of the McCormack Scale total score from baseline to day 3 follow-up visit. Participants without a 3-day measure were considered treatment failures.
Identification of Endometrial Microorganisms Present Obtained From Women With or Without Evidence of Endometritis.	enrollment	Identification of endometrial microorganisms present obtained from women with or without evidence of endometritis using a combination of culture methods, rRna sequencing and whole genomic sequencing. The aim is to identify the etiology of endometritis.

Trial Locations

Locations (3)

Magee-Womens Hospital of UPMC; 🇺🇸 Pittsburgh, Pennsylvania, United States

Allegheny County Health Department Sexually Transmitted Diseases Clinic; 🇺🇸 Pittsburgh, Pennsylvania, United States

UPMC Mercy Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States