AST-120 (spherical carbon adsorbent) in the treatment of perianal fistulae in mild-to-moderate Crohn's disease: FHAST-1, a phase 3, multicenter, placebo-controlled study.

Abstract

BACKGROUND:

AST-120 (spherical carbon adsorbent) was previously reported to be effective for perianal fistula healing in Japanese patients with mild-to-moderate Crohn's disease.

METHODS:

To evaluate the efficacy and safety of AST-120 in a Western population, a phase 3, multicenter, randomized, double-blind, placebo-controlled, study (FHAST-1) was conducted in adult patients with at least 1 draining perianal fistula and a Crohn's disease activity index <400. Patients received either AST-120 or matching placebo at a dose of 2 g 3 times daily for 8 weeks. The primary endpoint was the proportion of patients with treatment success, defined as a 50% reduction in the number of draining fistulae, at both weeks 4 and 8. A multivariate model was generated to assess covariates for treatment success among baseline variables.

RESULTS:

Two hundred forty-nine patients were randomized (AST-120; n = 122; placebo, n = 127). The proportions of patients achieving the primary endpoint were no different between treatment groups (13.9% versus 16.5%, P = 0.6). No differences in fistula response were noted at week 4 (23.0% versus 25.2%, P = 0.77) or week 8 (27.0 versus 34.6%, P = 0.22). Serum C-reactive protein concentrations >0.6 mg/dL and Crohn's disease activity index scores >151 at baseline were associated with a reduced likelihood of treatment success (odds ratio, 0.40; confidence interval, 0.19-0.87; P = 0.02; and odds ratio, 0.45; confidence interval, 0.21-0.97; P = 0.04, respectively).

CONCLUSIONS:

In this largest placebo-controlled trial to date to evaluate the impact of a therapeutic agent on perianal fistulae in Crohn's disease, the efficacy of AST-120 could not be confirmed. An inverse relationship was observed between both inflammatory and clinical disease activity and fistula response.

• Authors: Walter Reinisch, Simon Travis, Stephen Hanauer, Hong Wang, Nawar Shara, M Scott Harris
• Journal: Inflammatory bowel diseases (Inflamm Bowel Dis) Vol. 20 Issue 5 Pg. 872-81 (May 2014) ISSN: 1536-4844 [Electronic] England
• PMID: 24694794 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Gastrointestinal Agents
• Oxides
• Carbon
• AST 120

Topics

• Adolescent
• Adult
• Aged
• Carbon (therapeutic use)
• Crohn Disease (complications, pathology)
• Double-Blind Method
• Female
• Follow-Up Studies
• Gastrointestinal Agents (therapeutic use)
• Humans
• Male
• Microspheres
• Middle Aged
• Oxides (therapeutic use)
• Prospective Studies
• Rectal Fistula (drug therapy, etiology, metabolism)
• Treatment Outcome
• Young Adult