Topical Analgesia Post-Haemorrhoidectomy

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Hemorrhoid Pain, Hemorrhoids

Intervention / Treatment
-----------------
* Drug: Metronidazole cream
* Drug: Metronidazole and Diltiazem cream
* Drug: Metronidazole and Lidocaine cream
* Drug: Metronidazole, Diltiazem and Lidocaine cream


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 16 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: Parallel with 1:1:1:1 Allocation.
Masking: Double


Arms and Interventions

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

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 |