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

NCT ID: NCT01160640

Last Updated: 2018-07-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 233 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2015-08-31

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.

Conditions

Pelvic Inflammatory Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ceftriaxone/Doxycycline/Placebo Oral Cap

ceftrixone 250mg IM single dose plus doxycycline 100 mg PO bid x 14 days plus placebo oral capsule PO bid x 14 days

Group Type: PLACEBO_COMPARATOR

Ceftriaxone

Intervention Type: DRUG

ceftrixone 250mg IM single dose

Doxycycline

Intervention Type: DRUG

Doxycycline 100 mg PO bid x 14 days

Placebo Oral Capsule

Intervention Type: DRUG

placebo oral capsule PO bid x 14 days

Ceftriaxone, Doxycycline, 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

Group Type: ACTIVE_COMPARATOR

Ceftriaxone

Intervention Type: DRUG

ceftrixone 250mg IM single dose

Doxycycline

Intervention Type: DRUG

Doxycycline 100 mg PO bid x 14 days

Metronidazole

Intervention Type: DRUG

metronidazole 500 mg PO bid x 14 days

Interventions

Ceftriaxone

ceftrixone 250mg IM single dose

Intervention Type: DRUG

Doxycycline

Doxycycline 100 mg PO bid x 14 days

Intervention Type: DRUG

Metronidazole

metronidazole 500 mg PO bid x 14 days

Intervention Type: DRUG

Placebo Oral Capsule

placebo oral capsule PO bid x 14 days

Intervention Type: DRUG

Other Intervention Names

Rocephin; Flagyl

Eligibility Criteria

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

• Minimum Eligible Age: 15 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

Harold Wiesenfeld

OTHER

Sponsor Role: lead

Responsible Party

Harold Wiesenfeld

Associate Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Harold C Wiesenfeld, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

Allegheny County Health Department Sexually Transmitted Diseases Clinic

Pittsburgh, Pennsylvania, United States

Magee-Womens Hospital of UPMC

Pittsburgh, Pennsylvania, United States

UPMC Mercy Hospital

Pittsburgh, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 32052831 (View on PubMed)

Other Identifiers

1U19AI084024-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

PRO10010112

Identifier Type: -

Identifier Source: org_study_id