Clinical trial NCT03343509: Topical Versus Oral Metronidazole Following Excisional Haemorrhoidectomy
Official title: A Prospective, Multicentre, Double-Blinded Randomised Controlled Trial Comparing Topical Versus Oral Metronidazole in Reducing Post-Operative Pain Following Excisional Haemorrhoidectomy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hemorrhoids
Postoperative Pain
Keywords: Hemorrhoidectomy
Metronidazole
Postoperative analgesia
Lead sponsor: University of Auckland, New Zealand
Sponsor class: OTHER
First posted: 2017-11-17
Enrollment: 120
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Daily Post-Operative Pain
timeFrame: Day 7
Secondary outcomes:
measure: Total Analgesia Use
timeFrame: Day 7
measure: Complication Rates
timeFrame: Day 30
measure: Return to Normal Activity
timeFrame: Day 30 (Followed up until returned back to normal)
measure: Return of Bowel Function
timeFrame: Day 7
Other outcomes:
Locations:
city: Auckland
country: New Zealand
facility: Manukau SuperClinic, Counties Manukau District Health Board
city: Auckland
country: New Zealand
facility: Ormiston Hospital
Study officials:
affiliation: The University of Auckland
name: Andrew G Hill, MBChB
role: PRINCIPAL_INVESTIGATOR
References: