Evaluation of Topical 10% Metronidazole Ointment for the Treatment of Active Perianal Crohn's Disease

Phase III Study to Evaluate the Effect of 10% Metronidazole Ointment, Applied Topically Three Times a Day in and Around the Anus and the Change in Perianal Crohn's Disease Activity

The purpose of this study is to compare changes in Perianal Crohn's Disease following use of locally applied 10% metronidazole ointment and a placebo.

Study Overview

• Status: Completed
• Conditions: Crohn's Disease
• Intervention / Treatment: Drug: 10% Metronidazole Ointment

Detailed Description

Anorectal Crohn's disease is one of the most problematic and debilitating conditions encountered in colorectal practise. The condition is usually chronic, debilitating, and frequently refractory to current medications. Failure to respond to medical therapy may ultimately result in proctocolectomy and ileostomy, even in the absence of more proximal colonic disease. Isolated anorectal Crohn's disease is reported in 3 to 5% of Crohn's patients. In Crohn's patients as a whole, anorectal involvement is reported in up to one third to one half of patients, in addition to either colonic or enteric Crohn's disease. In spite of the previously reported painless nature of anorectal Crohn's disease, it is the author's experience that the condition can be inordinately painful due to deeply eroding fissures, oedematous skin tags, and painful induration of the perianal region.

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • Airdrie, United Kingdom, ML6 0JS
    • Monklands Hospital
  • Birmingham, United Kingdom, B9 5SS
    • Birmingham Heartlands Hospital
  • Bristol, United Kingdom, BS1 3NU
    • Bristol Royal Infirmary
  • Cardiff, United Kingdom, CF14 4XW
    • University Hospital of Wales
  • Coventry, United Kingdom, CV2 2DX
    • University Hospital of Warwick and Coventry
  • Harrow, United Kingdom, HA1 3UJ
    • St Marks Hospital
  • London, United Kingdom, SE1 &EH
    • St Thomas Hospital
  • Peterborough, United Kingdom, PE3 6DA
    • Peterborough District Hospital
  • Derbyshire
    • Derby, Derbyshire, United Kingdom, DE22 3NE
      • Derby City General Hospital
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE5 4PW
      • Leicester General Hospital
• United States
  • Missouri
    • St Louis, Missouri, United States, M 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have Crohn's disease (diagnosed by radiology, endoscopy and pathology), with anorectal involvement.
• Have had perianal symptoms for longer than 3 months
• Have a PCDAI of 5 or above at baseline
• Subjects can be on concomitant medication. Acceptable regimes are:-
• Aminosalicylates at a dosage that has been stable for more than 4 weeks before screening;
• Oral corticosteroids <40mg per day that has been stable for more than 3 weeks;
• Methotrexate given for at least 3 months that has been stable for more than 4 weeks; Azathioprine or mercaptopurine given for at least 6 months at dosage that has been stable for more than 8 weeks;
• Antibiotics at a dosage that has been stable for 4 weeks (subjects may be on oral metronidazole but on a dose not more than 750mg per day),
• Cycolsporin for more than 3 months and on a stable dose for more than 4 weeks;
• Patients who have been treated with Infliximab must have received their initial dose 3 months before starting study medication and their most recent dose at least 8 weeks before starting study medication and not receive an infusion whilst in the double-blind treatment phase of the study for 4 weeks. During the second 4 week open stage of the study patients can commence again a maintenance regime with Infliximab treatment if deemed necessary
• Any patients not on concurrent medication must have been off medication for at least 4 weeks before screening.
• If patients have Setons these must have been in place for at least 4 weeks prior to screening.
• Subjects must be aged 18 years or over and of the legal age of consent.
• If female, the subject must not be lactating and must be (a) post- menopausal, (b) surgically sterilised, or (c) have a negative pregnancy test result prior to entry into the study and will use double- barrier methods of contraception (two separate methods of birthcontrol one of which may include oral contraception) for the duration of the study.
• Must have provided written informed consent to participate.

Exclusion Criteria:

• They have had surgery to the anus or rectum in the past 4 weeks;
• They have a perianal abscess requiring incision and drainage;
• They have a stoma of less than 6 months duration;
• Allergic to metronidazole;
• Are taking any prohibited medication.
• Deemed mentally incompetent.
• Considered by their physician unlikely to be able to comply with the protocol.
• Taken part in an experimental drug study in the preceding three months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metronidazole 10% ointment	Drug: 10% Metronidazole Ointment; Metronidazole 10% ointment applied perianally three times daily for four weeks. Placebo ointment applied perianally three times daily for four weeks
Placebo Comparator: Placebo ointment	Drug: 10% Metronidazole Ointment; Metronidazole 10% ointment applied perianally three times daily for four weeks. Placebo ointment applied perianally three times daily for four weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the effect of 10% metronidazole ointment, applied topically three times a day, in and around the anus, on the change in perianal Crohn's disease activity.	Perianal Crohn's Disease Activity Index	Four weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate and compare the relief of perianal pain and discomfort associated with Crohn's disease, against placebo.	Perianal Crohn's Disease Activity Index plus Visual Analogue Scale for perianal pain	4 weeks
To evaluate and compare Patient Global Impression of Improvement	Patient Global Impression of Improvement (numerical scale)	4 weeks
To compare visual improvement (using photographic documentation assessed by a blinded independent observer)	Photographic record	4 weeks
To compare Quality of Life assessments	Short Form 12 Questionnaire	4 weeks
To evaluate and compare the number of analgesics required prior to treatment and to that required by the treatment and placebo group	Usage of analgesics during the treatment period	4 weeks
To evaluate and compare fistula healing	Visual assessment of fistula healing	4 weeks

Collaborators and Investigators

• Sponsor: S.L.A. Pharma AG
• Investigators: Principal Investigator: Emin Carapeti, BSc,MBBS,MD,, St Thomas Hospital, London

Publications and helpful links

General Publications

• Maeda Y, Ng SC, Durdey P, Burt C, Torkington J, Rao PK, Mayberry J, Moshkovska T, Stone CD, Carapeti E, Vaizey CJ; Topical Metronidazole in Perianal Crohn's Study Group. Randomized clinical trial of metronidazole ointment versus placebo in perianal Crohn's disease. Br J Surg. 2010 Sep;97(9):1340-7. doi: 10.1002/bjs.7121.

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (Actual): February 1, 2008
• Study Completion (Actual): February 1, 2008

Study Registration Dates

• First Submitted: July 30, 2007
• First Submitted That Met QC Criteria: July 30, 2007
• First Posted (Estimate): July 31, 2007

Study Record Updates

• Last Update Posted (Estimate): December 13, 2012
• Last Update Submitted That Met QC Criteria: December 12, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Metronidazole
• Other Study ID Numbers: MET/01

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