Topical Analgesia Post-Haemorrhoidectomy

A Prospective, Multicentre, Double-Blinded Randomised Controlled Trial Comparing Topical Metronidazole, Diltiazem and Lidocaine on Post-Operative Pain Following Excisional Haemorrhoidectomy

Symptomatic haemorrhoids, or piles, have significant effects on quality of life. The treatment for advanced disease is surgical excision (haemorrhoidectomy) which is extremely effective. However, pain following haemorrhoidectomy is known by all to be a miserable experience and current treatment is not very effective. We have formulated a new cream treatment which targets three theorised mechanisms of pain after haemorrhoidectomy. We will test the effectiveness of the treatments with a multi-centred randomised controlled factorial trial with four parallel double-blinded arms containing different combinations of the active agents. The outcomes include pain scores, amount of analgesia required and time to return to work. The results of our study could provide evidence of an effective treatment for post haemorrhoidectomy pain. The treatment may provide considerable benefit to patients undergoing this surgical procedure.

Study Overview

• Status: Completed
• Conditions: Hemorrhoids; Hemorrhoid Pain
• Intervention / Treatment: Drug: Metronidazole cream; Drug: Metronidazole and Diltiazem cream; Drug: Metronidazole and Lidocaine cream; Drug: Metronidazole, Diltiazem and Lidocaine cream

Detailed Description

Study Design: This will be a patient-and-investigator blinded factorial randomised trial with four parallel groups. Participants in all four groups will be instructed to apply cream 3 times a day for 7 days after surgery. A standard analgesia prescription will be provided with laxatives as per routine care. Patients will be provided a questionnaire to complete and return on day 14.

Random Sequence Generation: Computer generated sequence allocating patients to a 1:1:1:1 ratio using permuted block randomisation in blocks of 12.

Allocation Concealment: This randomisation code will be seeded to the pharmacist to who will package and label the cream according to a code. The creams will be indistinguishable to which active ingredient they contain.

Assignment of intervention: Patients will be assigned in order according to the numbering of the cream tubes by the blinded investigator.

Data recording: Data will be recorded on Redcap database.

• Study Type: Interventional
• Enrollment (Actual): 192
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• New Zealand
  • Auckland, New Zealand, 1041
    • Counties Manukau District Health Board

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥16
• All patients undergoing excisional haemorrhoidectomy

Exclusion Criteria:

• Age <16,
• history of chronic pain,
• drug allergy or idiosyncracies to any actives or excipients in
• cream,
• breastfeeding,
• any medical history which is a contraindication to any of metronidazole, lidocaine, or diltiazem including including:
• sick sinus syndrome,
• atrioventricular block,
• hypotension,
• heart failure and bradycardia.
• concomitant medications which are contraindicated to metronidazole, lidocaine or diltiazem.
• patients already taking diltiazem.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Metronidazole; Group A receiving 10% metronidazole cream	Drug: Metronidazole cream; 10% metronidazole applied rectally
Active Comparator: Metronidazole + Diltiazem; Metronidazole 10% + Diltiazem 2%	Drug: Metronidazole and Diltiazem cream; Combination Metronidazole and Diltiazem applied rectally
Active Comparator: Metronidazole + Lignocaine; Metronidazole 10% + Lignocaine 4%	Drug: Metronidazole and Lidocaine cream; Combination metronidazole and lignocaine applied rectally
Active Comparator: Metronidazole + Diltiazem + Lignocaine; Metronidazole 10% + Diltiazem 2% + Lignocaine 4%	Drug: Metronidazole, Diltiazem and Lidocaine cream; Combination of all active agents tested applied rectally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain scores	Measured by visual analog scale, 1-10cm, continuous, the higher the score, the worse the pain	7 days
Amount of analgesic use	Morphine equivalent amount	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Return to work	Day post-operation when the patient returns to work	14 days
Pain on bowel motion: Visual Analog Scale	Measured by Visual Analog Scale, continuous 1-10cm, the higher the score, the worse the pain.	7 days
Complications	Rates of Bleeding	30 days
Re-admission	Rates of Re-admission to hospital,	30 days
Repeat Prescription	Rates of Repeat Prescription Requirement	30 days

Collaborators and Investigators

• Sponsor: University of Auckland, New Zealand
• Investigators: Principal Investigator: Andrew G Hill, MBChB, MD, EdD, FRACS, FACS, Counties Manukau Health

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Actual): February 1, 2022
• Study Completion (Actual): February 1, 2022

Study Registration Dates

• First Submitted: February 17, 2020
• First Submitted That Met QC Criteria: February 18, 2020
• First Posted (Actual): February 19, 2020

Study Record Updates

• Last Update Posted (Actual): May 18, 2022
• Last Update Submitted That Met QC Criteria: May 16, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Cardiovascular Diseases; Vascular Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases; Hemorrhoids; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Anti-Infective Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anti-Bacterial Agents; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Calcium-Regulating Hormones and Agents; Antiprotozoal Agents; Antiparasitic Agents; Calcium Channel Blockers; Lidocaine; Metronidazole; Diltiazem
• Other Study ID Numbers: RCT Haemorrhoidectomy

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Will be shared when results become available.
• IPD Sharing Time Frame: When results are available for 12 months
• IPD Sharing Access Criteria: email request
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

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