HemorrhoidsPhase 4NCT03343509
Topical Versus Oral Metronidazole Following Excisional Haemorrhoidectomy
A Phase 4 study testing Metronidazole Oral and Metronidazole Ointment in people with Hemorrhoids and Postoperative Pain, run by University of Auckland, New Zealand at 2 sites in New Zealand.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Hemorrhoids, Postoperative Pain
- What is being tested?
- Metronidazole Oral and Metronidazole Ointment
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 2 sitesNew Zealand
- Study dates
- 11 Mar 2019to 1 Feb 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- All patients undergoing excisional haemorrhoidectomy
Who cannot join
- < 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
Trial locations and contacts
2 sites in 1 country.
New Zealand2 sites
Manukau SuperClinic, Counties Manukau District Health Board
Auckland
Ormiston Hospital
Auckland
About this study
Official title: A Prospective, Multicentre, Double-Blinded Randomised Controlled Trial Comparing Topical Versus Oral Metronidazole in Reducing Post-Operative Pain Following Excisional Haemorrhoidectomy
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.
Read the 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.
- Conditions
- Hemorrhoids, Postoperative Pain
- Being tested
- Metronidazole Oral, Metronidazole Ointment, Placebo Oral Tablet, Placebo Ointment
- Keywords
- Hemorrhoidectomy, Metronidazole, Postoperative analgesia
- Medical subject headings
- Hemorrhoids, Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metronidazole OralDrug
Oral Metronidazole
Metronidazole OintmentDrug
Metronidazole Ointment
Placebo Oral TabletDrug
Placebo Tablet
Placebo OintmentDrug
Placebo Ointment
| Study group | Role | What they receive |
|---|---|---|
| Group A - Oral | Experimental | Oral metronidazole 400mg 3 times a day for 7 days Placebo ointment applied 3 time times a day for 7 days to affected region Receives: Drug: Metronidazole Oral; Drug: Placebo Ointment |
| Group B - Topical | Experimental | Topical metronidazole ointment 10% 3 times a day for 7 days Oral placebo tablets 3 times a day for 7 days Receives: Drug: Metronidazole Ointment; Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Daily Post-Operative Pain
Daily Post-Operative Pain Measured on Visual Analogue Scale (0 to 10)
Measured: Day 7
Secondary outcomes (4)
Total Analgesia Use
Measured in Morphine Equivalent Doses
Measured: Day 7
Complication Rates
Short term complication rates including adverse reactions, bleeding, paraesthesiae, urinary retention, readmission
Measured: Day 30
Return to Normal Activity
Time to return back to normal activity
Measured: Day 30 (Followed up until returned back to normal)
Return of Bowel Function
Time for first bowel motion
Measured: Day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2017
- Study start11 Mar 2019
- Primary completion1 Feb 2020
- Study completion1 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HemorrhoidsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Auckland, New Zealand
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Andrew G Hill, MBChB, MD (Thesis), EdD, FACS, FRACS, University of Auckland, New Zealand
- Investigators
- Andrew G Hill, MBChB, Principal investigator, The University of Auckland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03343509
- Sponsor's protocol ID
- MetHaemorrhoid
- Status last verified
- Nov 2020
- First submitted
- 5 Nov 2017
- Last updated
- 3 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Not to be shared
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Multicentre, Double-Blinded Randomised Controlled Trial Comparing Topical Versus Oral Metronidazole in Reducing Post-Operative Pain Following Excisional Haemorrhoidectomy
- ClinicalTrials.gov ID
- NCT03343509
- Acronym / sponsor ID
- MetHaemorrhoid
- Conditions
- Hemorrhoids, Postoperative Pain
- Keywords
- Hemorrhoidectomy, Metronidazole, Postoperative analgesia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- University of Auckland, New ZealandUniversity, hospital or other
- Study start
- 11 Mar 2019 (actual)
- Primary completion
- 1 Feb 2020 (actual)
- Study completion
- 1 Feb 2020 (actual)
- First posted
- 17 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A - Oral | Experimental | Drug: Metronidazole Oral, Drug: Placebo 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 - Topical | Experimental | Drug: Metronidazole Ointment, Drug: Placebo Oral TabletTopical metronidazole ointment 10% 3 times a day for 7 days Oral placebo tablets 3 times a day for 7 days |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- All patients undergoing excisional haemorrhoidectomy
Key exclusion criteria (5 listed)
- < 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metronidazole OralOral Metronidazole | Drug | Group A - Oral |
| Metronidazole OintmentMetronidazole Ointment | Drug | Group B - Topical |
| Placebo Oral TabletPlacebo Tablet | Drug | Group B - Topical |
| Placebo OintmentPlacebo Ointment | Drug | Group A - Oral |
Primary outcome
Daily Post-Operative Pain
Time frame: Day 7
Daily Post-Operative Pain Measured on Visual Analogue Scale (0 to 10)
4 secondary outcomes
Total Analgesia Use
Time frame: Day 7
Complication Rates
Time frame: Day 30
Return to Normal Activity
Time frame: Day 30 (Followed up until returned back to normal)
Return of Bowel Function
Time frame: Day 7
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2020.
- Individual participant dataSharing planned: No. Not to be shared
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew G Hill, MBChB principal investigator
The University of Auckland
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Metronidazole Oral and Metronidazole Ointment in people with Hemorrhoids and Postoperative Pain, run by University of Auckland, New Zealand at 2 sites in New Zealand.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Daily Post-Operative Pain (time frame: Day 7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2020.