Topical Versus Oral Metronidazole Following Excisional Haemorrhoidectomy

• ClinicalTrials.gov Identifier: NCT03343509
• Recruitment Status: Completed
• First Posted: November 17, 2017
• Last Update Posted: November 3, 2020
• Sponsor: University of Auckland, New Zealand
• Information provided by (Responsible Party): Andrew G Hill, MBChB, MD (Thesis), EdD, FACS, FRACS, University of Auckland, New Zealand

Study Description

Brief Summary:

This study aims to determine if topical metronidazole reduces pain more than oral metronidazole following excisional haemorrhoidectomy. The trial will be a multi-centered, patient and investigator blinded superiority trial with two parallel groups and a primary outcome of pain scores during 14 days after surgery.

Group A will receive oral metronidazole and placebo cream. Group B will receive placebo tablets and topical metronidazole cream.

Condition or disease	Intervention/treatment	Phase
Hemorrhoids; Postoperative Pain	Drug: Metronidazole Oral; Drug: Metronidazole Ointment; Drug: Placebo Oral Tablet; Drug: Placebo Ointment	Phase 4

Detailed Description:

The pathogenesis of post-operative excisional haemorrhoidectomy pain is multi-factorial with secondary bacterial colonisation, inflammation and anal sphincter spasm/hypertonicity all purposed to play a role. Several pharmacological agents have been introduced in the last two decades targeting specific parts of the hypothesized pathway of pain pathogenesis showing promising improvements.

Metronidazole is part of the nitroimidazole class of antibiotics and primarily affects anaerobic bacteria and protozoa and traditionally has been used in surgical prophylaxis and treating anaerobic infections. It has been postulated to decrease pain following EH via two mechanisms; first by decreasing secondary bacterial colonisation and hence reducing post-operative inflammation; and second via a hitherto poorly understood direct anti-inflammatory response. The oral route has been initially investigated but topical administration has more recently been mooted for analgesia and theoretically reduces the unpleasant systemic side effects of oral administration. Our research group has recently completed a systematic review of both oral and topical administration of metronidazole. This review showed benefit in reducing postoperative haemorrhoidectomy pain from both routes of administration but this far there has been no comparison of the two routes.

Metronidazole has been proposed to have both anti-bacterial and pleiotropic anti-inflammatory properties but its precise mechanism of action is unknown. The increased understanding of this novel use of an agent with a known pharmacological profile will generally broaden our use of a simple, cheap and widespread agent. The investigators hope research into this drug will enable its use beyond that of haemorrhoidectomies, with possible pleiotropic applications into other similar operations.

Given the high prevalence of haemorrhoids in a vital segment of New Zealand's population, this research will contribute to improved outcomes for affected patients. Decreasing the significant post-operative pain will improve the quality of life for New Zealanders as well as affected populations worldwide. Socially and financially, it will enable earlier return to normal activity and reduce the burden on visits and readmissions to primary and secondary care, respectively.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Prospective, Multicentre, Double-Blinded Randomised Controlled Trial Comparing Topical Versus Oral Metronidazole in Reducing Post-Operative Pain Following Excisional Haemorrhoidectomy
• Actual Study Start Date: March 11, 2019
• Actual Primary Completion Date: February 1, 2020
• Actual Study Completion Date: February 1, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group A - Oral; Oral metronidazole 400mg 3 times a day for 7 days Placebo ointment applied 3 time times a day for 7 days to affected region	Drug: Metronidazole Oral; Oral Metronidazole; Drug: Placebo Ointment; Placebo Ointment
Experimental: Group B - Topical; Topical metronidazole ointment 10% 3 times a day for 7 days Oral placebo tablets 3 times a day for 7 days	Drug: Metronidazole Ointment; Metronidazole Ointment; Drug: Placebo Oral Tablet; Placebo Tablet

Outcome Measures

Primary Outcome Measures :

1. Daily Post-Operative Pain [ Time Frame: Day 7 ]
   Daily Post-Operative Pain Measured on Visual Analogue Scale (0 to 10)

Secondary Outcome Measures :

1. Total Analgesia Use [ Time Frame: Day 7 ]
   Measured in Morphine Equivalent Doses
2. Complication Rates [ Time Frame: Day 30 ]
   Short term complication rates including adverse reactions, bleeding, paraesthesiae, urinary retention, readmission
3. Return to Normal Activity [ Time Frame: Day 30 (Followed up until returned back to normal) ]
   Time to return back to normal activity
4. Return of Bowel Function [ Time Frame: Day 7 ]
   Time for first bowel motion

Eligibility Criteria

• Ages Eligible for Study: 16 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• All patients undergoing excisional haemorrhoidectomy

Exclusion Criteria:

• < 16 years of age
• Have a simultaneous operation other than excisional haemorrhoidectomy
• History of chronic pain
• Previous allergy/adverse reaction to metronidazole
• Patients unable to consent or complete data questionnaires due to cognitive impairment

Contacts and Locations

Locations

New Zealand

Manukau SuperClinic, Counties Manukau District Health Board

Auckland, New Zealand

Ormiston Hospital

Auckland, New Zealand

Sponsors and Collaborators

University of Auckland, New Zealand

Investigators

• Principal Investigator: Andrew G Hill, MBChB; The University of Auckland

More Information

• Responsible Party: Andrew G Hill, MBChB, MD (Thesis), EdD, FACS, FRACS, Professor, University of Auckland, New Zealand
• ClinicalTrials.gov Identifier: NCT03343509
• Other Study ID Numbers: MetHaemorrhoid
• First Posted: November 17, 2017
• Last Update Posted: November 3, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Not to be shared

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Andrew G Hill, MBChB, MD (Thesis), EdD, FACS, FRACS, University of Auckland, New Zealand:

Hemorrhoidectomy; Metronidazole; Postoperative analgesia

Additional relevant MeSH terms:

Hemorrhoids; Rectal Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Vascular Diseases; Cardiovascular Diseases; Metronidazole; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents