Double-blind crossover trial of metronidazole versus placebo in chronic unremitting pouchitis

Abstract

Metronidazole has been used to treat pouchitis, but there are no controlled data that show it is effective. Chronic unremitting pouchitis is a form of the disorder particularly difficult to manage. Diarrhea is the main symptom of pouchitis, which results from acute inflammation of the mucosa of an ileal reservoir. To test the hypothesis that metronidazole (400 mg thrice daily for seven days) is no better than placebo at reducing stool frequency in chronic unremitting pouchitis, a double-blind placebo-controlled crossover study has been performed. Thirteen patients who had undergone restorative proctocolectomy for ulcerative colitis were studied. The diagnosis of pouchitis was based on clinical, endoscopic, and histological criteria. At entry all patients had symptomatic pouchitis and were passing more than six stools/24 hr or had consistently bloody stools with at least four of six endoscopic criteria of mucosal inflammation. The median frequency of defecation decreased by 3 bowel actions/24 hr (conservative 95% confidence intervals 0-4/24 hr) on metronidazole but increased by a median of 1/24 hr on placebo. The difference between the median number of bowel motions, when treatment with metronidazole was compared to placebo, was 4 motions/24 hr (P < 0.05) in favor of metronidazole. There was no significant change in the endoscopic or histological grade of inflammation, in the serum C-reactive protein level, or symptomatic scores. In a parallel study, metronidazole did not alter stool frequency in asymptomatic patients without pouchitis who had endoscopically normal reservoirs (six polyposis, six colitis).(ABSTRACT TRUNCATED AT 250 WORDS)

Ulcerative Colitis Practice Guidelines in Adults: American College of Gastroenterology, Practice Parameters Committee

“…Metronidazole in a dose of 400 mg three times daily ( 349 ) or 20 mg / kg per day ( 347 ) is eff ective in the treatment of chronic active pouchitis; in clinical practice, metronidazole in a dose of 250 mg three times daily is oft en used ( 329,349 ). Controlled trials showed at least similar effi cacy with ciprofl oxacin 500 mg twice daily ( 347 ), or with budesonide enema 2 g daily (not available in the United States) ( 350 ).…”

Both Preoperative Perinuclear Antineutrophil Cytoplasmic Antibody and Anti-CBir1 Expression in Ulcerative Colitis Patients Influence Pouchitis Development After Ileal Pouch–Anal Anastomosis

“…Bacterial overgrowth occurs universally in pelvic pouches (3,4) yet patients with familial polyposis patients almost never develop pouchitis (1). Selected patients who develop pouchitis can be successfully treated with antibiotics, probiotics or even immune modulating agents (5)(6)(7)(8). Finally, diversion of the fecal stream in patients with refractory pouchitis is almost always successful (9).…”

Bismuth carbomer foam enemas for active chronic pouchitis: a randomized, double‐blind, placebo‐controlled trial

“…6 In the second study, 13 patients with chronic pouchitis were treated in a double-blind crossover trial with metronidazole 400 mg three times daily or placebo for 14 days, and there was a signi®cant reduction in stool frequency with metronidazole. 7 In the latter study, 55% of the metronidazole-treated patients developed side-effects, including nausea, vomiting, abdominal discomfort and skin rash. Chronic administration of metronidazole at a high dose of 20 mg/kg per day for the treatment of Crohn's disease caused symptomatic peripheral neuropathy in up to 85% of patients, and is a limiting factor in using maintenance metronidazole to suppress chronic pouchitis.…”

“…5 There are only two placebo-controlled trials, both using metronidazole. 6,7 In one study a single patient with chronic pouchitis was treated in a blinded crossover`n of 1' trial with signi®cantly worse symptoms with placebo compared to metronidazole 250 mg daily. 6 In the second study, 13 patients with chronic pouchitis were treated in a double-blind crossover trial with metronidazole 400 mg three times daily or placebo for 14 days, and there was a signi®cant reduction in stool frequency with metronidazole.…”