Clinical trial NCT01160640: The Importance of Anti-anaerobic Therapy for Acute Pelvic Inflammatory Disease (PID)
Official title: The Importance of Anti-anaerobic Therapy for Acute PID
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pelvic Inflammatory Disease
Keywords: PID
Pelvic Inflammatory Disease
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2010-07-12
Enrollment: 233
Sex: FEMALE
Minimum age (years): 15
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Clearance of Anaerobic Organisms From the Endometrium
timeFrame: Enrollment to 30 days
Secondary outcomes:
measure: The Prevalence of M. Genitalium in the Cervix and Endometrium From Women With Acute PID.
timeFrame: enrollment
measure: The Eradication of M. Genitalium From the Lower and Upper Genital Tract Following Antibiotic Therapy for Acute PID.
timeFrame: Enrollment to 30 days
measure: Resolution of Clinical Signs and Symptoms of Acute PID - Intention to Treat Analysis
timeFrame: Enrollment to 3 day follow up visit
measure: Identification of Endometrial Microorganisms Present Obtained From Women With or Without Evidence of Endometritis.
timeFrame: enrollment
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Allegheny County Health Department Sexually Transmitted Diseases Clinic
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Magee-Womens Hospital of UPMC
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Mercy Hospital
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Harold C Wiesenfeld, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wiesenfeld HC, Meyn LA, Darville T, Macio IS, Hillier SL. A Randomized Controlled Trial of Ceftriaxone and Doxycycline, With or Without Metronidazole, for the Treatment of Acute Pelvic Inflammatory Disease. Clin Infect Dis. 2021 Apr 8;72(7):1181-1189. doi: 10.1093/cid/ciaa101.