Please note the ANZCTR will be unattended from Friday 20 December 2019 for the holidays. The Registry will re-open on Tuesday 07 January 2020. Submissions and updates will not be processed during that time.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12619000735156
Ethics application status
Approved
Date submitted
9/05/2019
Date registered
16/05/2019
Date last updated
16/05/2019
Date data sharing statement initially provided
16/05/2019
Date results information initially provided
16/05/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Post-haemorrhoidectomy Pain and Metronidazole Trial
Scientific title
Efficacy of oral metronidazole for patients with post-haemorrhoidectomy pain: a double-blinded, randomised controlled trial
Secondary ID [1] 298167 0
None
Universal Trial Number (UTN)
Trial acronym
PPM Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Post-haemorrhoidectomy pain 312727 0
Haemorrhoids
312816 0
Condition category
Condition code
Oral and Gastrointestinal 311229 311229 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Anaesthesiology 311314 311314 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
400mg oral metronidazole three times daily versus placebo for 7 days post-haemorrhoidectomy in addition to standard analgesic care for both groups.

Standard analgesic regimen is as follows; 1000mg oral paracetamol four times a day, 50mg diclofenac three times a day for 7-10 days, one macrogol 3350 13.8g sachet daily, oxycodone 5mg 6-hourly as required (20 tablets supplied).

No specific monitoring strategies regarding compliance for the intervention drug was established. Patients were counselled to complete the course of trial medication as prescribed and also to report any potential side-effects. A list of common side-effects was included with the patient information and consent for and also contained within the trial questionnaire.
Intervention code [1] 314395 0
Treatment: Drugs
Comparator / control treatment
Matching placebo (composed of 'Avicel' microcrystalline cellulose) capsules three times daily for 7 days
Control group
Placebo

Outcomes
Primary outcome [1] 319987 0
Daily pain scores for 21 days on a numerical rating scale
Timepoint [1] 319987 0
Day of operation to 21 days post-operatively
Secondary outcome [1] 370113 0
Overall satisfaction with surgery via satisfaction survey at routine post-operative follow-up appointment

Satisfaction was measured on a 7-point scale from very dissatisfied, dissatisfied, slightly dissatisfied, not sure, slightly satisfied, satisfied to very satisfied. This scale was modified from a previous study examining surgical satisfaction post-haemorrhoidectomy.
Timepoint [1] 370113 0
4 weeks post-operatively
Secondary outcome [2] 370363 0
Surgical complications via study specific questionnaire, clinical examination at routine post-operative follow-up appointment and medical records

Complications include bleeding, infection, urinary retention, faecal incontinence or constipation, anal canal stenosis
Timepoint [2] 370363 0
Up to 4 weeks post-operatively
Secondary outcome [3] 370364 0
Medication related side-effects study specific questionnaire, patient history at routine post-operative follow-up appointment and medical records

Possible side-effects abdominal discomfort, nausea, vomiting, headache, rash or itch
Timepoint [3] 370364 0
Up to 4 weeks post-operatively

Eligibility
Key inclusion criteria
Males and females between 18-70 years of age undergoing elective haemorrhoidectomy and able to provide voluntary consent for the procedure and to participate in the trial.
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Renal impairment (eGFR <50, severe ischemic heart disease, active peptic ulcer disease, alcoholism and IV opiate dependency, severe aspirin-sensitive asthma, pregnant women, institutionalised patients, patients unable to provide consent, patients with chronic pain conditions, hypersensitivity or known intolerance to metronidazole, NSAIDs or oxycodone.

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)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a random number generator via computer software
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
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Continuous and ordinal variables were compared using a Mann-Whitney test, with reporting of median values and interquartile ranges. Categorical variables were compared using Fisher’s exact test, with presentation of percentage values. To assess significance of change over the time-course of the trial of pain and defaecation pain scores, we employed multilevel mixed effects modelling utilizing the “xtmixed” command in STATA. This permits assessment of the significance of both changes in patients’ individual pain scores as a function of time and separately as the interaction of time with treatment allocation (placebo versus metronidazole).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 13693 0
Box Hill Hospital - Box Hill
Recruitment hospital [2] 13694 0
Maroondah Hospital - Ringwood East
Recruitment hospital [3] 13695 0
Angliss Hospital - Upper Ferntree Gully
Recruitment postcode(s) [1] 26385 0
3128 - Box Hill
Recruitment postcode(s) [2] 26386 0
3135 - Ringwood East
Recruitment postcode(s) [3] 26387 0
3156 - Upper Ferntree Gully

Funding & Sponsors
Funding source category [1] 302702 0
Hospital
Name [1] 302702 0
Colorectal Unit, Department of Surgery, Eastern Health
Address [1] 302702 0
Box Hill Hospital, 5 Arnold St, Box Hill VIC 3128
Country [1] 302702 0
Australia
Primary sponsor type
Individual
Name
Bruce Wilkie
Address
C/O Department of Surgery, Box Hill Hospital, 5 Arnold St, Box Hill VIC 3128
Country
Australia
Secondary sponsor category [1] 302631 0
None
Name [1] 302631 0
Address [1] 302631 0
Country [1] 302631 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303312 0
Eastern Health Human Research and Ethic s Committee
Ethics committee address [1] 303312 0
8 Arnold St, Box Hill VIC 3128
Ethics committee country [1] 303312 0
Australia
Date submitted for ethics approval [1] 303312 0
Approval date [1] 303312 0
27/08/2014
Ethics approval number [1] 303312 0
E02/2014

Summary
Brief summary
Pain is an expected problem after haemorrhoidectomy surgery and there have been a number of studies that have examined metronidazole in helping to reduce post-operative pain. The results are conflicting and the purpose of this study is to further examine the role of oral metronidazole plus standardised analgesia in reducing post-heamorrhoidectomy pain and compare its efficacy to placebo plus standardised analgesia.
Trial website
None
Trial related presentations / publications
Public notes
e-Poster: Wilkie B, Chandra R, Lam D, Chua J, Keck J, ‘Post-haemorrhoidectomy Pain and Metronidazole (PPM Trial): Protocol design for a double-blind randomised controlled trial’, Australian Scientific Congress, Royal Australasian College of Surgeons, Adelaide May 2017

Contacts
Principal investigator
Name 93230 0
Dr Bruce Wilkie
Address 93230 0
C/O Department of Surgery, Box Hill Hospital, 5 Arnold St, Box Hill VIC 3128
Country 93230 0
Australia
Phone 93230 0
+61 431235672
Fax 93230 0
Email 93230 0
brucedwilkie@gmail.com
Contact person for public queries
Name 93231 0
Dr Bruce Wilkie
Address 93231 0
C/O Department of Surgery, Box Hill Hospital, 5 Arnold St, Box Hill VIC 3128
Country 93231 0
Australia
Phone 93231 0
+61 431235672
Fax 93231 0
Email 93231 0
brucedwilkie@gmail.com
Contact person for scientific queries
Name 93232 0
Dr Bruce Wilkie
Address 93232 0
C/O Department of Surgery, Box Hill Hospital, 5 Arnold St, Box Hill VIC 3128
Country 93232 0
Australia
Phone 93232 0
+61 431235672
Fax 93232 0
Email 93232 0
brucedwilkie@gmail.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
This was not included in the study design and ethics proposal
What supporting documents are/will be available?
Study protocol
Statistical analysis plan
Informed consent form
Ethical approval
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary
Of 88 patients enrolled in the study, forty patients (19 placebo patients, 21 metronidazole patients) completed the trial and returned the survey questionnaire (45.5%). There were no differences between groups with regards to age, gender, smoking status, self-reported general health, self-reported general quality of life, haemorrhoid-related pain, haemorrhoid-related impact on quality of life, surgery received (Milligan-Morgan or Ferguson technique), treating surgeon, rate of surgical complications, satisfaction with surgery, experience of surgery, median overall pain score, overall impression of pain control, and likelihood of recommending surgery to other patients.
With regards to reported worst pain scores, differences were seen between groups on days 16 and 18-21 with the metronidazole group reporting less pain. Defaecation-related pain followed a similar pattern with the metronidazole group reporting less pain on days 16, 18 and 19.
Multilevel mixed effects modelling was utilised to determine whether the interaction of time with treatment allocation was relevant. Using this method of analysis, the impact of time on median worst pain score was identified to more important that treatment allocation, i.e. being prescribed placebo versus metronidazole did not affect the improvement in patients’ reported pain.