Topical Versus Oral Metronidazole Following Excisional Haemorrhoidectomy

A Prospective, Multicentre, Double-Blinded Randomised Controlled Trial Comparing Topical Versus Oral Metronidazole in Reducing Post-Operative Pain Following Excisional Haemorrhoidectomy

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.

Study Overview

• Status: Completed
• Conditions: Postoperative Pain; Hemorrhoids
• Intervention / Treatment: Drug: Metronidazole Oral; Drug: Placebo Ointment; Drug: Metronidazole Ointment; Drug: Placebo Oral Tablet

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 Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• New Zealand
  • Auckland, New Zealand
    • Manukau SuperClinic, Counties Manukau District Health Board
  • Auckland, New Zealand
    • Ormiston Hospital

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Daily Post-Operative Pain	Daily Post-Operative Pain Measured on Visual Analogue Scale (0 to 10)	Day 7

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Auckland, New Zealand
• Investigators: Principal Investigator: Andrew G Hill, MBChB, The University of Auckland

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2019
• Primary Completion (Actual): February 1, 2020
• Study Completion (Actual): February 1, 2020

Study Registration Dates

• First Submitted: November 5, 2017
• First Submitted That Met QC Criteria: November 11, 2017
• First Posted (Actual): November 17, 2017

Study Record Updates

• Last Update Posted (Actual): November 3, 2020
• Last Update Submitted That Met QC Criteria: November 2, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Metronidazole; Postoperative analgesia; Hemorrhoidectomy
• Additional Relevant MeSH Terms: Digestive System Diseases; Cardiovascular Diseases; Vascular Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases; Hemorrhoids; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Metronidazole
• Other Study ID Numbers: MetHaemorrhoid

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Not to be shared

Drug and device information, study documents

• 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