EndometriosisPhase 4NCT04554693
The Use of Low Dose Metronidazole to Decrease Postoperative Pain After Endometriosis Surgery
A Phase 4 study testing Metronidazole Oral in people with Endometriosis and Endometriosis-related Pain, run by University of Louisville at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Endometriosis, Endometriosis-related Pain
- What is being tested?
- Metronidazole Oral
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 78 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Oct 2020to 5 Oct 2023
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Louisville Hospital
Louisville, Kentucky, 40202
About this study
Official title: The Use of Low Dose Metronidazole to Decrease Postoperative Pain After Endometriosis Surgery: A Prospective, Randomized, Placebo-Controlled Trial
The purpose of this study is to determine a difference in participant reported pain after endometriosis surgery in participants given oral metronidazole versus placebo.
Read the 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.
- Conditions
- Endometriosis, Endometriosis-related Pain
- Being tested
- Metronidazole Oral, Placebo
- Medical subject headings
- Endometriosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metronidazole OralDrug
250 mg oral three times a day for 14 days
PlaceboDrug
Halal and Kosher certified gelatin placebo capsules oral three times a day for 14 days
| Study group | Role | What they receive |
|---|---|---|
| Metronidazole | Experimental | Metronidazole Receives: Drug: Metronidazole Oral |
| Placebo | Placebo comparator | Halal and Kosher certified gelatin placebo capsules Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With 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.
Measured: 6 weeks postoperatively.
Secondary outcomes (4)
Quality of Life Via Endometriosis Health Profile-5
Endometriosis Health Profile-5 on scale of 0-100, with higher scores meaning worse outcome, using continuous variables reported as means.
Measured: 6 weeks postoperatively.
Sexual Health Via Female Sexual Function Index
Female sexual function index on a scale of 2-36 with higher scores meaning higher sexual dysfunction
Measured: 6 weeks postoperatively.
Percentage of Participants With 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.
Measured: 6 months postoperatively.
Percentage of Participants With 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.
Measured: 1 year postoperatively.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2020
- Study start19 Oct 2020
- Primary completion5 Oct 2023
- Study completion5 Oct 2023
Why it stopped: Principal investigator did not have the necessary staffing resources to continue the study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for EndometriosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Louisville
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Resad Pasic, University of Louisville
- Investigators
- Resad Pasic, MD, PhD, Principal investigator, University of Louisville
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04554693
- Sponsor's protocol ID
- 200544
- Status last verified
- May 2026
- First submitted
- 5 Sep 2020
- Last updated
- 18 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 22819144Working 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.
PubMed 31486802Practice bulletin no. 114: management of endometriosis. Obstet Gynecol. 2010 Jul;116(1):223-236. doi: 10.1097/AOG.0b013e3181e8b073. No abstract available.
PubMed 20567196Abbott 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.
PubMed 15482763Sutton 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.
PubMed 7926075Quaranta 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.
PubMed 31827467Leonardi 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.
PubMed 31454452Chadchan 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.
PubMed 31037294Simoens 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.
PubMed 17584822Nogueira F, Sharghi S, Kuchler K, Lion T. Pathogenetic Impact of Bacterial-Fungal Interactions. Microorganisms. 2019 Oct 16;7(10):459. doi: 10.3390/microorganisms7100459.
PubMed 31623187Mert 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.
PubMed 30069974Moloney 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.
PubMed 26662472Guo 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.
PubMed 31551115Glick 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.
PubMed 30809655Quevedo A, Parikh S, Reinstine J, Chamseddine P, Gaskins JT, Whalen C, Biscette S, Pasic RP. The impact of metronidazole on pain persistence after fertility-sparing endometriosis surgery: METROFERT randomized study. Am J Obstet Gynecol. 2025 Jan;232(1):106.e1-106.e9. doi: 10.1016/j.ajog.2024.07.006. Epub 2024 Jul 15.
PubMed 39019388
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Use of Low Dose Metronidazole to Decrease Postoperative Pain After Endometriosis Surgery: A Prospective, Randomized, Placebo-Controlled Trial
- ClinicalTrials.gov ID
- NCT04554693
- Acronym / sponsor ID
- 200544
- Conditions
- Endometriosis, Endometriosis-related Pain
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Principal investigator did not have the necessary staffing resources to continue the study.
- Enrolment
- 78 participants (actual)
- Lead sponsor
- University of LouisvilleUniversity, hospital or other
- Study start
- 19 Oct 2020 (actual)
- Primary completion
- 5 Oct 2023 (actual)
- Study completion
- 5 Oct 2023 (actual)
- First posted
- 18 Sep 2020 (actual)
- Results
- Posted 18 Jun 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metronidazole | Experimental | Drug: Metronidazole OralMetronidazole |
| Placebo | Placebo comparator | Drug: PlaceboHalal and Kosher certified gelatin placebo capsules |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (13 listed)
- Refusal to surgery
- Contraindication to surgery
- Known allergy to metronidazole
- Known allergy to any component in gelatin placebo capsules
- Scheduled hysterectomy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metronidazole Oral250 mg oral three times a day for 14 days | Drug | Metronidazole |
| PlaceboHalal and Kosher certified gelatin placebo capsules oral three times a day for 14 days | Drug | Placebo |
Primary outcome
Percentage of Participants With Self Reported Pain Persistence
Time frame: 6 weeks postoperatively.
The outcome of binary, subject pain persistence, assessed as yes or no, will be compared between groups using the Fisher exact test.
4 secondary outcomes
Quality of Life Via Endometriosis Health Profile-5
Time frame: 6 weeks postoperatively.
Sexual Health Via Female Sexual Function Index
Time frame: 6 weeks postoperatively.
Percentage of Participants With Self Reported Pain Persistence
Time frame: 6 months postoperatively.
Percentage of Participants With Self Reported Pain Persistence
Time frame: 1 year postoperatively.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22819144Burney 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.
- Background: PubMed 31486802Working 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.
- Background: PubMed 20567196Practice bulletin no. 114: management of endometriosis. Obstet Gynecol. 2010 Jul;116(1):223-236. doi: 10.1097/AOG.0b013e3181e8b073. No abstract available.
- Background: PubMed 15482763Abbott 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.
- Background: PubMed 7926075Sutton 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.
- Background: PubMed 31827467Quaranta 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.
- Background: PubMed 31454452Leonardi 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.
- Background: PubMed 31037294Chadchan 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.
- Background: PubMed 17584822Simoens 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.
- Background: PubMed 31623187Nogueira F, Sharghi S, Kuchler K, Lion T. Pathogenetic Impact of Bacterial-Fungal Interactions. Microorganisms. 2019 Oct 16;7(10):459. doi: 10.3390/microorganisms7100459.
- Background: PubMed 30069974Mert 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.
- Background: PubMed 26662472Moloney 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Resad Pasic, MD, PhD principal investigator
University of Louisville
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Metronidazole Oral in people with Endometriosis and Endometriosis-related Pain, run by University of Louisville at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Self Reported Pain Persistence (time frame: 6 weeks postoperatively.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04554693, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2026.