search
Back to results

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

Primary Purpose

Pelvic Inflammatory Disease

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ceftriaxone
Doxycycline
Metronidazole
Placebo Oral Capsule
Sponsored by
Harold Wiesenfeld
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pelvic Inflammatory Disease focused on measuring PID, Pelvic Inflammatory Disease

Eligibility Criteria

15 Years - 40 Years (Child, Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Allegheny County Health Department Sexually Transmitted Diseases Clinic
  • Magee-Womens Hospital of UPMC
  • UPMC Mercy Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Ceftriaxone/Doxycycline/Placebo Oral Cap

Ceftriaxone, Doxycycline, Metronidazole

Arm Description

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

ceftriaxone 250 mg IM single dose plus doxycycline 100 mg PO bid x 14 days plus metronidazole 500 mg PO bid x 14 days

Outcomes

Primary Outcome Measures

Clearance of Anaerobic Organisms From the Endometrium
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

The Prevalence of M. Genitalium in the Cervix and Endometrium From Women With Acute PID.
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.
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
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.
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.

Full Information

First Posted
July 8, 2010
Last Updated
July 6, 2018
Sponsor
Harold Wiesenfeld
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
search

1. Study Identification

Unique Protocol Identification Number
NCT01160640
Brief Title
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

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
November 2010 (undefined)
Primary Completion Date
August 2015 (Actual)
Study Completion Date
August 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Harold Wiesenfeld
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pelvic Inflammatory Disease
Keywords
PID, Pelvic Inflammatory Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
233 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ceftriaxone/Doxycycline/Placebo Oral Cap
Arm Type
Placebo Comparator
Arm Description
ceftrixone 250mg IM single dose plus doxycycline 100 mg PO bid x 14 days plus placebo oral capsule PO bid x 14 days
Arm Title
Ceftriaxone, Doxycycline, Metronidazole
Arm Type
Active Comparator
Arm Description
ceftriaxone 250 mg IM single dose plus doxycycline 100 mg PO bid x 14 days plus metronidazole 500 mg PO bid x 14 days
Intervention Type
Drug
Intervention Name(s)
Ceftriaxone
Other Intervention Name(s)
Rocephin
Intervention Description
ceftrixone 250mg IM single dose
Intervention Type
Drug
Intervention Name(s)
Doxycycline
Intervention Description
Doxycycline 100 mg PO bid x 14 days
Intervention Type
Drug
Intervention Name(s)
Metronidazole
Other Intervention Name(s)
Flagyl
Intervention Description
metronidazole 500 mg PO bid x 14 days
Intervention Type
Drug
Intervention Name(s)
Placebo Oral Capsule
Intervention Description
placebo oral capsule PO bid x 14 days
Primary Outcome Measure Information:
Title
Clearance of Anaerobic Organisms From the Endometrium
Description
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.
Time Frame
Enrollment to 30 days
Secondary Outcome Measure Information:
Title
The Prevalence of M. Genitalium in the Cervix and Endometrium From Women With Acute PID.
Description
The number of women who had M. genitalium detected in cervical and endometrial biopsy cultures by nucleic acid amplification tests at enrollment.
Time Frame
enrollment
Title
The Eradication of M. Genitalium From the Lower and Upper Genital Tract Following Antibiotic Therapy for Acute PID.
Description
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.
Time Frame
Enrollment to 30 days
Title
Resolution of Clinical Signs and Symptoms of Acute PID - Intention to Treat Analysis
Description
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.
Time Frame
Enrollment to 3 day follow up visit
Title
Identification of Endometrial Microorganisms Present Obtained From Women With or Without Evidence of Endometritis.
Description
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.
Time Frame
enrollment

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
15 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Women must meet all of the following inclusion criteria: 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) Acute PID, defined by symptoms and signs guided by current CDC guidelines:50 Current symptoms of lower abdominal or pelvic pain (present for ≤30 days) AND Cervical motion tenderness AND/OR uterine tenderness AND/OR adnexal tenderness on pelvic examination Ability to provide written informed consent Exclusion Criteria: Women with any of the following will be ineligible to participate: Pregnant or nursing a baby (Note: a urine pregnancy test will be done at enrollment. Result must be negative to participate in the study.) Uterine procedure (e.g. dilation and curettage, abortion) or miscarriage within the past 6 weeks. 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. Systemic or vaginal antibiotic therapy in the preceding 7 days Requires inpatient PID therapy (per the current CDC guidelines)50 Inability to obtain an endometrial biopsy at enrollment Known inability to comply with the follow-up visits Prior hysterectomy 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) Inability to swallow pills Not willing to refrain from alcohol during the two week treatment period (and two additional days following completion of study medication) Other condition present at enrollment that requires additional antibiotic treatment 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) Any condition, in the opinion of the investigator that would interfere with the participant's safety or with study outcomes 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 Previous participation in this study Evidence of a tuboovarian abscess
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Harold C Wiesenfeld, MD
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
Allegheny County Health Department Sexually Transmitted Diseases Clinic
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Magee-Womens Hospital of UPMC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
UPMC Mercy Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15219
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32052831
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs