Results of a phase III trial comparing tolevamer, vancomycin and metronidazole in patients with Clostridium difficile-associated diarrhoea
Abstract number: O464
Bouza E., Dryden M., Mohammed R., Peppe J., Chasan-Taber S., Donovan J., Davidson D., Short G.
Objectives:Clostridium difficile-associated diarrhoea (CDAD) is an increasing nosocomial problem. Treatment with vancomycin (V) or metronidazole (M) is associated with incomplete response rates, frequent recurrences, and selection for resistant bacteria. In this study, the safety and efficacy of tolevamer (T) liquid (Genzyme, Cambridge MA), a novel non-antibiotic toxin binder, was compared to V and M.
Methods: In this double-blind, multicentre (Europe, Australia, Canada) study in adult patients with acute CDAD appropriate for oral therapy, patients were randomised (2:1:1) to T 9g (3g tid, 14 days), V 500 mg (125mg qid, 10 days), or M 1500mg (375 mg qid, 10 days). In the T group, an initial 9 g loading dose was given. Patients were followed for recurrence 4 weeks after treatment cessation. The primary endpoint was non-inferiority of T vs. V for clinical success, defined as resolution of diarrhoea and absence of severe abdominal discomfort due to CDAD on Day 10.
Results: 528 patients (268 T, 125 V and 135 M) comprised the intent-to-treat population. At enrollment, CDAD was noted as mild (31%), moderate (43%), or severe (25%), first occurrence (83%) or recurrent (17%), and was similar across the treatment groups. Clinical success rates were 42% (112/268) T, 81% (101/125) V, and 73% (99/135) M, indicating similar success rates in the V and M groups (p =0.153), but a lower T success rate than V or M (p 0.001 for both comparators). In patients with CDAD resolution sustained through the end of active treatment, the recurrence rates were 6% for T, 18% for V, and 19% for M. Adverse events were similar across treatment arms.
Conclusion: T did not meet its primary endpoint of non-inferiority vs. V. Overall, V and M had similar responses. Recurrent CDAD occurred frequently with V and M, but was uncommon among those patients who resolved with T, suggesting that flora-sparing drugs may help reduce recurrences. These results confirm those from an identically designed parallel study performed in the US and Canada (ICAAC 2007; poster 3826).
|Session name:||18th European Congress of Clinical Microbiology and Infectious Diseases|
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