Florian Beigel1, Niels Teich2, Stefanie Howaldt3, Frank Lammert4, Jochen Maul5, Simone Breiteneicher6, Christian Rust7, Burkhard Göke6, Stephan Brand6, Thomas Ochsenkühn8. 1. Department of Medicine II, University Hospital Munich-Grosshadern, Ludwig-Maximilians-University Munich, Germany. Electronic address: florian.beigel@med.uni-muenchen.de. 2. Internal Practice, Leipzig, Germany. 3. Internal Practice, Hamburg, Germany. 4. Department of Medicine II, Saarland University Medical Center, Homburg, Germany. 5. Department for Gastroenterology, Infectious Diseases and Rheumatology Charité-Berlin, Campus Benjamin Franklin, Berlin, Germany. 6. Department of Medicine II, University Hospital Munich-Grosshadern, Ludwig-Maximilians-University Munich, Germany. 7. Department of Medicine II, University Hospital Munich-Grosshadern, Ludwig-Maximilians-University Munich, Germany; Department of Medicine II, Krankenhaus Barmherzige Brüder, Munich, Germany. 8. Department of Medicine II, University Hospital Munich-Grosshadern, Ludwig-Maximilians-University Munich, Germany; Isarmedizin Zentrum, Munich, Germany.
Abstract
BACKGROUND AND AIMS: Bile acid malabsorption (BAM)-associated diarrhea is an important clinical issue in patients with Crohn's disease (CD). We analyzed the efficacy and safety of the bile acid sequestrant colesevelam for treatment of BAM-associated diarrhea in CD patients in a randomized, double-blind, placebo-controlled study. METHODS: The primary endpoint was the proportion of patients with >30% reduction of liquid stools/day from baseline to termination visit at week 4. Secondary endpoints were reduction of the number of liquid stools/day, improvement of stool consistency and quality of life. RESULTS:26 patients were analyzed in the intention-to-treat (ITT) analysis. The primary endpoint was reached by 10 patients (69.7%) in the colesevelam group compared to 3 patients (27.3%) in the placebo group (risk difference RD=.394, 95%CI:[-0.012; 0.706]; P=.0566). In the per-protocol analysis (n=22), the risk difference was statistically significant (RD=.470, 95%CI:[0.018; 0.788], P(H0: RD=0)=0.0364; 95% CI:[1.3;54.7]). Regarding secondary endpoints, in the ITT population colesevelam-treated patients had a significant reduction of liquid stools/day at week 4 (median 5.0 to 2.0; P=0.01), while patients treated with placebo had no significant reduction (median 4.0 to 3.0; P=0.42). Significantly more patients in the colesevelam group had improvement of stool consistency of at least one level in the Bristol stool chart, as compared to the placebo group (P=0.003). CONCLUSIONS: We found significant differences in favor for colesevelam treatment compared to placebo treatment for CD patients with BAM regarding the reduction of the number of liquid stools/day and stool consistency. ClinicalTrials.gov number: NCT01203254.
RCT Entities:
BACKGROUND AND AIMS: Bile acid malabsorption (BAM)-associated diarrhea is an important clinical issue in patients with Crohn's disease (CD). We analyzed the efficacy and safety of the bile acid sequestrant colesevelam for treatment of BAM-associated diarrhea in CDpatients in a randomized, double-blind, placebo-controlled study. METHODS: The primary endpoint was the proportion of patients with >30% reduction of liquid stools/day from baseline to termination visit at week 4. Secondary endpoints were reduction of the number of liquid stools/day, improvement of stool consistency and quality of life. RESULTS: 26 patients were analyzed in the intention-to-treat (ITT) analysis. The primary endpoint was reached by 10 patients (69.7%) in the colesevelam group compared to 3 patients (27.3%) in the placebo group (risk difference RD=.394, 95%CI:[-0.012; 0.706]; P=.0566). In the per-protocol analysis (n=22), the risk difference was statistically significant (RD=.470, 95%CI:[0.018; 0.788], P(H0: RD=0)=0.0364; 95% CI:[1.3;54.7]). Regarding secondary endpoints, in the ITT population colesevelam-treated patients had a significant reduction of liquid stools/day at week 4 (median 5.0 to 2.0; P=0.01), while patients treated with placebo had no significant reduction (median 4.0 to 3.0; P=0.42). Significantly more patients in the colesevelam group had improvement of stool consistency of at least one level in the Bristol stool chart, as compared to the placebo group (P=0.003). CONCLUSIONS: We found significant differences in favor for colesevelam treatment compared to placebo treatment for CDpatients with BAM regarding the reduction of the number of liquid stools/day and stool consistency. ClinicalTrials.gov number: NCT01203254.
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