The Importance of Anti-anaerobic Therapy for Acute Pelvic Inflammatory Disease (PID)
Condition: Pelvic Inflammatory Disease
MeSH terms: Pelvic Inflammatory Disease; Pelvic Infection
Intervention: Ceftriaxone; Doxycycline; Metronidazole; Placebo Oral Capsule
Intervention description: ceftrixone 250mg IM single dose; Doxycycline 100 mg PO bid x 14 days; metronidazole 500 mg PO bid x 14 days; placebo oral capsule PO bid x 14 days
Intervention MeSH terms: Metronidazole; Doxycycline; Ceftriaxone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 233.0
Sex: Female
Minimum age: 15 Years
Maximum age: 40 Years
Healthy volunteers: No
Keywords: PID; Pelvic Inflammatory Disease

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.
    

Eligibility criteria:

        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