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Topical Versus Oral Metronidazole Following Excisional Haemorrhoidectomy

Phase 4
Completed
Conditions
Hemorrhoids
Postoperative Pain
Interventions
Drug: Placebo Oral Tablet
Drug: Placebo Ointment
Registration Number
NCT03343509
Lead Sponsor
University of Auckland, New Zealand
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
120
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Group A - OralMetronidazole OralOral metronidazole 400mg 3 times a day for 7 days Placebo ointment applied 3 time times a day for 7 days to affected region
Group B - TopicalPlacebo Oral TabletTopical metronidazole ointment 10% 3 times a day for 7 days Oral placebo tablets 3 times a day for 7 days
Group A - OralPlacebo OintmentOral metronidazole 400mg 3 times a day for 7 days Placebo ointment applied 3 time times a day for 7 days to affected region
Group B - TopicalMetronidazole OintmentTopical metronidazole ointment 10% 3 times a day for 7 days Oral placebo tablets 3 times a day for 7 days
Primary Outcome Measures
NameTimeMethod
Daily Post-Operative PainDay 7

Daily Post-Operative Pain Measured on Visual Analogue Scale (0 to 10)

Secondary Outcome Measures
NameTimeMethod
Total Analgesia UseDay 7

Measured in Morphine Equivalent Doses

Complication RatesDay 30

Short term complication rates including adverse reactions, bleeding, paraesthesiae, urinary retention, readmission

Return to Normal ActivityDay 30 (Followed up until returned back to normal)

Time to return back to normal activity

Return of Bowel FunctionDay 7

Time for first bowel motion

Trial Locations

Locations (2)

Ormiston Hospital

🇳🇿

Auckland, New Zealand

Manukau SuperClinic, Counties Manukau District Health Board

🇳🇿

Auckland, New Zealand

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