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Trial registered on ANZCTR


Registration number
ACTRN12623000514606
Ethics application status
Approved
Date submitted
25/04/2023
Date registered
18/05/2023
Date last updated
4/07/2024
Date data sharing statement initially provided
18/05/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Topical nifedipine for post haemorrhoidectomy pain relief
Scientific title
Topical nifedipine for post haemorrhoidectomy pain relief: a randomised, prospective, double-blind placebo trial protocol
Secondary ID [1] 309519 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Haemorrhoidectomy 329802 0
Pain 329803 0
Condition category
Condition code
Surgery 326702 326702 0 0
Other surgery
Anaesthesiology 326703 326703 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
To assess the efficacy of topical (0.5%) nifedipine ointment for reducing post haemorrhoidectomy pain. Participants will be instructed to apply a pea-sized amount of their ointment, using a glove, 1-1.5cm into the anus circumferentially, as well as to the external anus. This will be done twice a day for four weeks. Follow up will consist of post operative questionnaire's to complete.
Intervention code [1] 325950 0
Treatment: Drugs
Comparator / control treatment
Comparative placebo ointment consisting of pluronic lecithin organogel (PLO).
Control group
Placebo

Outcomes
Primary outcome [1] 334566 0
Post operative pain will be the primary outcome. This will be assessed using a validated 10-point standardised visual analogue scale (VAS). Scores will range from zero (no pain at all) to ten (worst pain imaginable).
Timepoint [1] 334566 0
Using the 10-point standardised VAS, pain will be measured at the following timepoints:
i. pre-operatively (baseline)
ii. recovery (within the first 30 minutes post-operatively)
iii. 4 hours (discharge) post-operatively
iv. 24 and 48hours post-operatively
v. 1 and 4 weeks post-operatively
Secondary outcome [1] 421238 0
Secondary outcomes will include the initial time of rescue oxycodone analgesia usage. This will be assessed by patient records and patient reporting.
Timepoint [1] 421238 0
This will be the first time-point, within 4 weeks post-operartively, when the patient uses rescue oxycodone.
Secondary outcome [2] 421842 0
Secondary outcomes will include the total rescue oxycodone usage. This will be assessed by patient records and patient reporting.
Timepoint [2] 421842 0
This will be the total amount of oxycodone consumed within 4 weeks post-operatively.
Secondary outcome [3] 421843 0
Secondary outcomes will include the time to first defecation. This will be assessed by patient records and patient reporting.
Timepoint [3] 421843 0
This will be the first time-point, within 4 weeks post-operatively, when the patient defecates.
Secondary outcome [4] 421844 0
Secondary outcomes will include any adverse events. This will be assessed by patient records and patient reporting survey.
Timepoint [4] 421844 0
This will be measure over the 4 weeks post-operatively. These will included any of the following:
o readmission
o reoperation
o urinary retention requiring catherisation
o perianal bleeding
o perianal swelling or oedema
o faecal incontinence
o tenesmus
o headache
o light-headedness or dizziness
o peripheral oedema

Eligibility
Key inclusion criteria
Patients over the age of 18 who are planned for 3-column haemorrhoidectomy, by a closed technique, will be recruited by surgeons during either their initial consultation for haemorrhoidectomy surgery or on the day of planned surgery.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who will not be included in the trial will be those who:
i. are under the age of 18
ii. are pregnant or breast feeding
iii. have concurrent non-haemorrhoidal anorectal disease
iv. have a known allergy to nifedipine
v. have comorbidities or take medications that are a contra-indication to nifedipine usage
vi. have impaired renal function where parecoxib is contra-indicated
vii. have a chronic pain condition requiring ongoing regular analgesia
viii. cannot provide informed consent
ix. cannot have a general anaesthetic

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Concealment of treatment and placebo ointments in de-identified, opaque and numbered containers.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated block randomisation.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3 / Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample calculation:

Compared to similar studies, pre-trial calculations established a required sample size of 48 (24 patients per group), based on alpha = 0.05 and power = 0.9 based on primary outcome (pain). Estimating an attrition rate of 20-25%, a sample size of 60 (30 per group) was chosen. The sample size was calculated utilizing STATA 17 (StataCorp, College Station, Texas 77845 USA) considering a two-tailed test.

Statistical analysis:

The statistical analysis for this study will be conducted using STATA 17 (StataCorp, College Station, Texas 77845 USA). To ensure the validity of our findings, we will first check the normality of the numeric variables using the Kolmogorov-Smirnov test, as well as descriptive measures of distribution such as skewness and kurtosis.

For presentation purposes, we will report mean (SD) for numeric normal variables, median (min-max) for non-normal variables, and frequency (percent) for categorical variables. To compare baseline measures and demographic variables between the two groups, we will use independent t-tests and Fisher-Freeman-Halton Exact tests where appropriate.

To assess the effect of the intervention, we will use two analysis of covariance (ANCOVA) models: model 1 will control for baseline measures (baseline adjusted), and model 2 will control for baseline measures and possible confounders (fully adjusted).

The study will utilize a two-way analysis of variance with repeated measures (RMANOVA) to evaluate the effect of the intervention, time, and their interactions on primary and secondary outcomes. The assumption of sphericity will be assessed using the Mauchly test and, to correct for any deviation from the assumption, Greenhouse-Geiser-based correction will be employed. Significant RMANOVA results will be followed by Sidak post-hoc tests.

We will also use an intention-to-treat (ITT) approach for all analyses, and will consider p values less than 0.05 to be statistically significant.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/09/2024
Actual
Date of last participant enrolment
Anticipated
30/05/2025
Actual
Date of last data collection
Anticipated
30/06/2025
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 24598 0
Cabrini Hospital - Malvern - Malvern
Recruitment postcode(s) [1] 40196 0
3144 - Malvern

Funding & Sponsors
Funding source category [1] 313713 0
University
Name [1] 313713 0
Cabrini Monash University (Department of Surgery)
Country [1] 313713 0
Australia
Primary sponsor type
Individual
Name
Dr Christopher Steen
Address
Cabrini Monash University Department of Surgery
154 Wattletree Road
Malvern, 3144
Victoria, Australia
Country
Australia
Secondary sponsor category [1] 315522 0
None
Name [1] 315522 0
N/a
Address [1] 315522 0
N/a
Country [1] 315522 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312886 0
Cabrini Research Governance
Ethics committee address [1] 312886 0
Research Governance Officer
Cabrini Research
Level 2, 154 Wattletree Rd
MALVERN VIC 3144
Ethics committee country [1] 312886 0
Australia
Date submitted for ethics approval [1] 312886 0
25/04/2023
Approval date [1] 312886 0
15/01/2024
Ethics approval number [1] 312886 0
Project 01-01-06-23
Ethics committee name [2] 315637 0
Monash Health Human Research Ethics Committee A
Ethics committee address [2] 315637 0
https://monashhealth.org/research/resources/resource-library/
Ethics committee country [2] 315637 0
Australia
Date submitted for ethics approval [2] 315637 0
01/11/2023
Approval date [2] 315637 0
08/11/2023
Ethics approval number [2] 315637 0
HREC/99377/MonH-2023-376381(v1)

Summary
Brief summary
Haemorrhoidectomy (surgical removal of haemorrhoid) is a common surgical procedure carried out by general and colorectal surgeons worldwide. Pain following haemorrhoidectomy is universal and problematic, causing absenteeism from work and school as well as a hospital readmission for pain relief. This is thought to be related to spasm of the anal sphincter muscles or creation of an anal fissure. Topical medications to aid in pain relief are well studied and accepted due to their ready availability and low side effects. Calcium channel blockers (CCB), such as diltiazem and nifedipine, are available in topical preparation, and are thought to aid in pain relief by decreasing muscle spasm. Whilst there are some studies accessing the role of CCB in post haemorrhoidectomy pain relief, most are focussed on diltiazem. Interestingly, nifedipine has reported better healing rates in anal fissure than diltiazem. This study aims to ascertain the effectiveness of topical nifedipine versus placebo as a post operative adjunct in the hopes of reducing pain experienced and reducing the post-operative short-term disability associated with haemorrhoidectomy.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 126222 0
Dr Christopher Steen
Address 126222 0
Cabrini Monash University Department of Surgery
154 Wattletree Rd
Malvern, 3144
Victoria
Country 126222 0
Australia
Phone 126222 0
+61 395081786
Fax 126222 0
Email 126222 0
[email protected]
Contact person for public queries
Name 126223 0
Christopher Steen
Address 126223 0
Cabrini Monash University Department of Surgery
154 Wattletree Rd
Malvern, 3144
Victoria
Country 126223 0
Australia
Phone 126223 0
+61 395081222
Fax 126223 0
Email 126223 0
[email protected]
Contact person for scientific queries
Name 126224 0
Christopher Steen
Address 126224 0
Cabrini Monash University Department of Surgery
154 Wattletree Rd
Malvern, 3144
Victoria
Country 126224 0
Australia
Phone 126224 0
+61 395081222
Fax 126224 0
Email 126224 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All de-identified individual line-by-line data.
When will data be available (start and end dates)?
Immediately following publication, no end date determined.
Available to whom?
Researchers who provide a sound proposal.
Available for what types of analyses?
Meta-analyses.
How or where can data be obtained?
By contact with principal investigation ([email protected])


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.