Journal Article

Tolevamer, a Novel Nonantibiotic Polymer, Compared with Vancomycin in the Treatment of Mild to Moderately Severe <i>Clostridium difficile</i>–Associated Diarrhea

Thomas J. Louie, Jennifer Peppe, C. Kevin Watt, David Johnson, Rasheed Mohammed, Gordon Dow, Karl Weiss, Stuart Simon, Joseph F. John, Gary Garber, Scott-Chasan Taber and David M. Davidson

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 43, issue 4, pages 411-420
Published in print August 2006 | ISSN: 1058-4838
Published online August 2006 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/506349
Tolevamer, a Novel Nonantibiotic Polymer, Compared with Vancomycin in the Treatment of Mild to Moderately Severe Clostridium difficile–Associated Diarrhea

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  • Immunology
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Background. Current antibiotic therapies for Clostridium difficile–associated diarrhea have limitations, including progression to severe disease, recurrent C. difficile–associated diarrhea, and selection for nosocomial pathogens. Tolevamer, a soluble, high–molecular weight, anionic polymer that binds C. difficile toxins A and B is a unique nonantibiotic treatment option.

Methods. In this 3-arm, multicenter, randomized, double-blind, active-controlled, parallel-design phase II study, patients with mild to moderately severe C. difficile–associated diarrhea were randomized to receive 3 g of tolevamer per day (n = 97), 6 g of tolevamer per day (n = 95), or 500 mg of vancomycin per day (n = 97). The primary efficacy parameter was time to resolution of diarrhea, defined as the first day of 2 consecutive days when the patient had hard or formed stools (any number) or ⩽2 stools of loose or watery consistency.

Results. In the per-protocol study population, resolution of diarrhea was achieved in 48 (67%) of 72 patients receiving 3 g of tolevamer per day (median time to resolution of diarrhea, 4.0 days; 95% confidence interval, 2.0–6.0 days), in 58 (83%) of 70 patients receiving 6 g of tolevamer per day (median time to resolution of diarrhea, 2.5 days; 95% confidence interval, 2.0–3.0 days), and in 73 (91%) of 80 patients receiving vancomycin (median time to resolution of diarrhea, 2.0 days; 95% confidence interval, 1.0–3.0 days). Tolevamer administered at a dosage of 6 g per day was found to be noninferior to vancomycin administered at a dosage of 500 mg per day with regard to time to resolution of diarrhea (P = .02) and was associated with a trend toward a lower recurrence rate. Tolevamer was well tolerated but was associated with an increased risk of hypokalemia.

Conclusions. Tolevamer, a novel polystyrene binder of C. difficile toxins A and B, effectively treats mild to moderate C. difficile diarrhea and merits further clinical development.

Journal Article.  5113 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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