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

Study Description

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Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Crohn's Disease	Drug: 10% Metronidazole Ointment	Phase 3

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	74 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	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
Study Start Date :	May 2005
Actual Primary Completion Date :	February 2008
Actual Study Completion Date :	February 2008

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Metronidazole 10% ointment; 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; 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

Outcome Measures

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Primary Outcome Measures :

1. 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. [ Time Frame: Four weeks ]
   Perianal Crohn's Disease Activity Index

Secondary Outcome Measures :

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

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

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Locations

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

Sponsors and Collaborators

S.L.A. Pharma AG

Investigators

Principal Investigator:	Emin Carapeti, BSc,MBBS,MD,	St Thomas Hospital, London

More Information

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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Responsible Party:	S.L.A. Pharma AG
ClinicalTrials.gov Identifier:	NCT00509639 History of Changes
Other Study ID Numbers:	MET/01
First Posted:	July 31, 2007
Last Update Posted:	December 13, 2012
Last Verified:	December 2012

Additional relevant MeSH terms:

Crohn Disease; Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases	Intestinal Diseases; Metronidazole; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents