The Use of Low Dose Metronidazole to Decrease Postoperative Pain After Endometriosis Surgery

Endometriosis Clinical Trial

Official title:

The Use of Low Dose Metronidazole to Decrease Postoperative Pain After Endometriosis Surgery: A Prospective, Randomized, Placebo-Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04554693
• Other study ID #: 200544
• Status: Recruiting
• Phase: Phase 4
• Start date: October 19, 2020
• Est. completion date: September 2027

Study information

• Verified date: October 2023
• Source: University of Louisville
• Contact: Amira Quevedo, MD
• Phone: 5025884400
• Email: amira.quevedo[@]uoflhealth.org
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: September 2027
• Est. primary completion date: September 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Endometriosis
• Endometriosis-related Pain
• Pain, Postoperative

Intervention

Drug:
• Metronidazole Oral
250 mg oral three times a day for 14 days
• Placebo
Halal and Kosher certified gelatin placebo capsules oral three times a day for 14 days

Locations

Country	Name	City	State
United States	University of Louisville Hospital	Louisville	Kentucky

Sponsors (1)

Lead Sponsor	Collaborator
University of Louisville

Country where clinical trial is conducted

United States, 

References & Publications (14)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Practice bulletin no. 114: management of endometriosis. Obstet Gynecol. 2010 Jul;116(1):223-236. doi: 10.1097/AOG.0b013e3181e8b073. No abstract available. — View 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. — View 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. — View 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. — View 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. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Fertility	Number of pregnancies and miscarriages postoperatively will be compared	6 months postoperatively
Other	Fertility	Number of pregnancies and miscarriages postoperatively will be compared	1 year postoperatively
Other	Fertility	Number of pregnancies and miscarriages postoperatively will be compared	5 years postoperatively
Primary	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.	6 weeks postoperatively.
Secondary	Quality of life scores	Endometriosis Health Profile-5 on scale of 1-100 with higher scores meaning worse outcome	1 year postoperatively.
Secondary	Quality of life scores	Endometriosis Health Profile-5 on scale of 1-100 with higher scores meaning worse outcome	6 months postoperatively.
Secondary	Quality of life scores	Endometriosis Health Profile-5 on scale of 1-100 with higher scores meaning worse outcome	6 weeks postoperatively.
Secondary	Quality of life scores	Endometriosis Health Profile-5 on scale of 1-100 with higher scores meaning worse outcome	5 years postoperatively.
Secondary	Sexual health	Female sexual function index on a scale of 0-36 with higher scores meaning higher sexual dysfunction	6 weeks postoperatively.
Secondary	Sexual health	Female sexual function index on a scale of 0-36 with higher scores meaning higher sexual dysfunction	6 months postoperatively.
Secondary	Sexual health	Female sexual function index on a scale of 0-36 with higher scores meaning higher sexual dysfunction	1 year postoperatively.
Secondary	Sexual health	Female sexual function index on a scale of 0-36 with higher scores meaning higher sexual dysfunction	5 year postoperatively.
Secondary	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.	1 year postoperatively.
Secondary	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.	6 months postoperatively.