The Use of Low Dose Metronidazole to Decrease Postoperative Pain After Endometriosis Surgery
Primary Purpose
Endometriosis, Endometriosis-related Pain
Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Metronidazole Oral
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Endometriosis
Eligibility Criteria
Inclusion Criteria:
- Able to give informed consent
- Women aged 18-50 years old
- Scheduled to undergo excision of endometriosis
- Able to read and write in English and or Spanish
- Pain score > 2 on a 10 point visual analogue scale at baseline
- Negative screening by CAGE questionnaire
Exclusion Criteria:
- Refusal to surgery
- Contraindication to surgery
- Known allergy to metronidazole
- Known allergy to any component in gelatin placebo capsules
- Scheduled hysterectomy
- Endometriosis excision surgery within the last 3 months
- Elevated serum creatinine
- Abnormal liver function test greater than 2 times the normal
- Current pregnancy
- Breastfeeding
- Use of Disulfiram within the last 2 weeks
- History of Cockayne syndrome
- Inability to abstain from alcohol during the use of study drug
Sites / Locations
- University of Louisville HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Metronidazole
Placebo
Arm Description
Metronidazole
Halal and Kosher certified gelatin placebo capsules
Outcomes
Primary Outcome Measures
Self-reported pain persistence
The outcome of binary, subject pain persistence, assessed as yes or no, will be compared between groups using the Fisher exact test.
Secondary Outcome Measures
Quality of life scores
Endometriosis Health Profile-5 on scale of 1-100 with higher scores meaning worse outcome
Quality of life scores
Endometriosis Health Profile-5 on scale of 1-100 with higher scores meaning worse outcome
Quality of life scores
Endometriosis Health Profile-5 on scale of 1-100 with higher scores meaning worse outcome
Quality of life scores
Endometriosis Health Profile-5 on scale of 1-100 with higher scores meaning worse outcome
Sexual health
Female sexual function index on a scale of 0-36 with higher scores meaning higher sexual dysfunction
Sexual health
Female sexual function index on a scale of 0-36 with higher scores meaning higher sexual dysfunction
Sexual health
Female sexual function index on a scale of 0-36 with higher scores meaning higher sexual dysfunction
Sexual health
Female sexual function index on a scale of 0-36 with higher scores meaning higher sexual dysfunction
Self-reported pain persistence
The outcome of binary, subject pain persistence, assessed as yes or no, will be compared between groups using the Fisher exact test.
Self-reported pain persistence
The outcome of binary, subject pain persistence, assessed as yes or no, will be compared between groups using the Fisher exact test.
Full Information
NCT ID
NCT04554693
First Posted
September 5, 2020
Last Updated
March 1, 2022
Sponsor
University of Louisville
1. Study Identification
Unique Protocol Identification Number
NCT04554693
Brief Title
The Use of Low Dose Metronidazole to Decrease Postoperative Pain After Endometriosis Surgery
Official Title
The Use of Low Dose Metronidazole to Decrease Postoperative Pain After Endometriosis Surgery: A Prospective, Randomized, Placebo-Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 19, 2020 (Actual)
Primary Completion Date
September 2027 (Anticipated)
Study Completion Date
September 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Louisville
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to determine a difference in participant reported pain after endometriosis surgery in participants given oral metronidazole versus placebo.
Detailed Description
The study is a prospective, randomized, placebo-controlled trial. Women scheduled for endometriosis surgery between 18-50 years of age will be invited to participate in the study.
Participants with surgically staged endometriosis will be randomized to the metronidazole plus routine postoperative care arm or the placebo plus routine postoperative care arm. Participants will take study or placebo drug for a total of 14 days.
Participants will complete surveys at baseline and postoperatively at 6 weeks, 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years reporting intensity of endometriosis associated pain on a visual analog scale, pregnancy outcomes, quality of life, and sexual health.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Endometriosis, Endometriosis-related Pain
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
90 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Metronidazole
Arm Type
Experimental
Arm Description
Metronidazole
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Halal and Kosher certified gelatin placebo capsules
Intervention Type
Drug
Intervention Name(s)
Metronidazole Oral
Intervention Description
250 mg oral three times a day for 14 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Halal and Kosher certified gelatin placebo capsules oral three times a day for 14 days
Primary Outcome Measure Information:
Title
Self-reported pain persistence
Description
The outcome of binary, subject pain persistence, assessed as yes or no, will be compared between groups using the Fisher exact test.
Time Frame
6 weeks postoperatively.
Secondary Outcome Measure Information:
Title
Quality of life scores
Description
Endometriosis Health Profile-5 on scale of 1-100 with higher scores meaning worse outcome
Time Frame
1 year postoperatively.
Title
Quality of life scores
Description
Endometriosis Health Profile-5 on scale of 1-100 with higher scores meaning worse outcome
Time Frame
6 months postoperatively.
Title
Quality of life scores
Description
Endometriosis Health Profile-5 on scale of 1-100 with higher scores meaning worse outcome
Time Frame
6 weeks postoperatively.
Title
Quality of life scores
Description
Endometriosis Health Profile-5 on scale of 1-100 with higher scores meaning worse outcome
Time Frame
5 years postoperatively.
Title
Sexual health
Description
Female sexual function index on a scale of 0-36 with higher scores meaning higher sexual dysfunction
Time Frame
6 weeks postoperatively.
Title
Sexual health
Description
Female sexual function index on a scale of 0-36 with higher scores meaning higher sexual dysfunction
Time Frame
6 months postoperatively.
Title
Sexual health
Description
Female sexual function index on a scale of 0-36 with higher scores meaning higher sexual dysfunction
Time Frame
1 year postoperatively.
Title
Sexual health
Description
Female sexual function index on a scale of 0-36 with higher scores meaning higher sexual dysfunction
Time Frame
5 year postoperatively.
Title
Self-reported pain persistence
Description
The outcome of binary, subject pain persistence, assessed as yes or no, will be compared between groups using the Fisher exact test.
Time Frame
1 year postoperatively.
Title
Self-reported pain persistence
Description
The outcome of binary, subject pain persistence, assessed as yes or no, will be compared between groups using the Fisher exact test.
Time Frame
6 months postoperatively.
Other Pre-specified Outcome Measures:
Title
Fertility
Description
Number of pregnancies and miscarriages postoperatively will be compared
Time Frame
6 months postoperatively
Title
Fertility
Description
Number of pregnancies and miscarriages postoperatively will be compared
Time Frame
1 year postoperatively
Title
Fertility
Description
Number of pregnancies and miscarriages postoperatively will be compared
Time Frame
5 years postoperatively
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
Female participants
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Able to give informed consent
Women aged 18-50 years old
Scheduled to undergo excision of endometriosis
Able to read and write in English and or Spanish
Pain score > 2 on a 10 point visual analogue scale at baseline
Negative screening by CAGE questionnaire
Exclusion Criteria:
Refusal to surgery
Contraindication to surgery
Known allergy to metronidazole
Known allergy to any component in gelatin placebo capsules
Scheduled hysterectomy
Endometriosis excision surgery within the last 3 months
Elevated serum creatinine
Abnormal liver function test greater than 2 times the normal
Current pregnancy
Breastfeeding
Use of Disulfiram within the last 2 weeks
History of Cockayne syndrome
Inability to abstain from alcohol during the use of study drug
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Amira Quevedo, MD
Phone
5025884400
Email
amira.quevedo@uoflhealth.org
First Name & Middle Initial & Last Name or Official Title & Degree
Resad Pasic, MD, PhD
Phone
5025884400
Email
resad.pasic@louisville.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Resad Pasic, MD, PhD
Organizational Affiliation
University of Louisville
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Louisville Hospital
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
AMIRA QUEVEDO, MD
Phone
502-588-4400
Email
amira.quevedo@uoflhealth.org
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
22819144
Citation
Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012 Sep;98(3):511-9. doi: 10.1016/j.fertnstert.2012.06.029. Epub 2012 Jul 20.
Results Reference
background
PubMed Identifier
31486802
Citation
Working group of ESGE, ESHRE and WES; Saridogan E, Becker CM, Feki A, Grimbizis GF, Hummelshoj L, Keckstein J, Nisolle M, Tanos V, Ulrich UA, Vermeulen N, De Wilde RL. Recommendations for the Surgical Treatment of Endometriosis. Part 1: Ovarian Endometrioma. Hum Reprod Open. 2017 Dec 19;2017(4):hox016. doi: 10.1093/hropen/hox016. eCollection 2017.
Results Reference
background
PubMed Identifier
20567196
Citation
Practice bulletin no. 114: management of endometriosis. Obstet Gynecol. 2010 Jul;116(1):223-236. doi: 10.1097/AOG.0b013e3181e8b073. No abstract available.
Results Reference
background
PubMed Identifier
15482763
Citation
Abbott J, Hawe J, Hunter D, Holmes M, Finn P, Garry R. Laparoscopic excision of endometriosis: a randomized, placebo-controlled trial. Fertil Steril. 2004 Oct;82(4):878-84. doi: 10.1016/j.fertnstert.2004.03.046.
Results Reference
background
PubMed Identifier
7926075
Citation
Sutton CJ, Ewen SP, Whitelaw N, Haines P. Prospective, randomized, double-blind, controlled trial of laser laparoscopy in the treatment of pelvic pain associated with minimal, mild, and moderate endometriosis. Fertil Steril. 1994 Oct;62(4):696-700. doi: 10.1016/s0015-0282(16)56990-8.
Results Reference
background
PubMed Identifier
31827467
Citation
Quaranta G, Sanguinetti M, Masucci L. Fecal Microbiota Transplantation: A Potential Tool for Treatment of Human Female Reproductive Tract Diseases. Front Immunol. 2019 Nov 26;10:2653. doi: 10.3389/fimmu.2019.02653. eCollection 2019.
Results Reference
background
PubMed Identifier
31454452
Citation
Leonardi M, Hicks C, El-Assaad F, El-Omar E, Condous G. Endometriosis and the microbiome: a systematic review. BJOG. 2020 Jan;127(2):239-249. doi: 10.1111/1471-0528.15916. Epub 2019 Sep 19.
Results Reference
background
PubMed Identifier
31037294
Citation
Chadchan SB, Cheng M, Parnell LA, Yin Y, Schriefer A, Mysorekar IU, Kommagani R. Antibiotic therapy with metronidazole reduces endometriosis disease progression in mice: a potential role for gut microbiota. Hum Reprod. 2019 Jun 4;34(6):1106-1116. doi: 10.1093/humrep/dez041.
Results Reference
background
PubMed Identifier
17584822
Citation
Simoens S, Hummelshoj L, D'Hooghe T. Endometriosis: cost estimates and methodological perspective. Hum Reprod Update. 2007 Jul-Aug;13(4):395-404. doi: 10.1093/humupd/dmm010.
Results Reference
background
PubMed Identifier
31623187
Citation
Nogueira F, Sharghi S, Kuchler K, Lion T. Pathogenetic Impact of Bacterial-Fungal Interactions. Microorganisms. 2019 Oct 16;7(10):459. doi: 10.3390/microorganisms7100459.
Results Reference
background
PubMed Identifier
30069974
Citation
Mert I, Walther-Antonio M, Mariani A. Case for a role of the microbiome in gynecologic cancers: Clinician's perspective. J Obstet Gynaecol Res. 2018 Sep;44(9):1693-1704. doi: 10.1111/jog.13701. Epub 2018 Aug 2.
Results Reference
background
PubMed Identifier
26662472
Citation
Moloney RD, Johnson AC, O'Mahony SM, Dinan TG, Greenwood-Van Meerveld B, Cryan JF. Stress and the Microbiota-Gut-Brain Axis in Visceral Pain: Relevance to Irritable Bowel Syndrome. CNS Neurosci Ther. 2016 Feb;22(2):102-17. doi: 10.1111/cns.12490. Epub 2015 Dec 10.
Results Reference
background
PubMed Identifier
31551115
Citation
Guo R, Chen LH, Xing C, Liu T. Pain regulation by gut microbiota: molecular mechanisms and therapeutic potential. Br J Anaesth. 2019 Nov;123(5):637-654. doi: 10.1016/j.bja.2019.07.026. Epub 2019 Sep 21.
Results Reference
background
PubMed Identifier
30809655
Citation
Glick LR, Sossenheimer PH, Ollech JE, Cohen RD, Hyman NH, Hurst RD, Rubin DT. Low-Dose Metronidazole is Associated With a Decreased Rate of Endoscopic Recurrence of Crohn's Disease After Ileal Resection: A Retrospective Cohort Study. J Crohns Colitis. 2019 Sep 19;13(9):1158-1162. doi: 10.1093/ecco-jcc/jjz047.
Results Reference
background
Learn more about this trial
The Use of Low Dose Metronidazole to Decrease Postoperative Pain After Endometriosis Surgery
We'll reach out to this number within 24 hrs