Tolevamer, a novel nonantibiotic polymer, compared with vancomycin in the treatment of mild to moderately severe Clostridium difficile-associated diarrhea.

Abstract

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 < 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.

• Authors: Thomas J Louie, Jennifer Peppe, C Kevin Watt, David Johnson, Rasheed Mohammed, Gordon Dow, Karl Weiss, Stuart Simon, Joseph F John Jr, Gary Garber, Scott Chasan-Taber, David M Davidson, Tolevamer Study Investigator Group
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 43 Issue 4 Pg. 411-20 (Aug 15 2006) ISSN: 1537-6591 [Electronic] United States
• PMID: 16838228 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Infective Agents
• Bacterial Proteins
• Bacterial Toxins
• Enterotoxins
• Ions
• Polymers
• Polystyrenes
• Sulfonic Acids
• tcdA protein, Clostridium difficile
• toxB protein, Clostridium difficile
• Vancomycin
• styrenesulfonic acid polymer

Topics

• Adult
• Aged
• Aged, 80 and over
• Anti-Infective Agents (therapeutic use)
• Bacterial Proteins (metabolism)
• Bacterial Toxins (metabolism)
• Clostridioides difficile
• Diarrhea (drug therapy, microbiology)
• Double-Blind Method
• Enterocolitis, Pseudomembranous (drug therapy, microbiology)
• Enterotoxins (metabolism)
• Female
• Humans
• Ions (therapeutic use)
• Male
• Middle Aged
• Polymers (therapeutic use)
• Polystyrenes (therapeutic use)
• Sulfonic Acids
• Vancomycin (therapeutic use)