Fidaxomicin Versus Vancomycin for the Treatment of Clostridium Difficile-Associated Diarrhea (CDAD) (MK-5119-018)

The primary objective of this pivotal study is to investigate the safety and efficacy of fidaxomicin versus vancomycin in subjects with Clostridium difficile-associated diarrhea (CDAD). The cure rates at end of therapy and recurrence rates will be evaluated and compared.

• Fidaxomicin (Drug), also known as PAR-101, OPT-80, Dificid®: 200 mg oral capsules two times daily (q12h regimen)
• Vancomycin (Drug): 125 mg capsules q6hr (4 times a day)
• Matching Placebo to Fidaxomicin (Drug): Matching Placebo to Fidaxomicin administered two times daily (intermittently with fidaxomicin dosing)

Primary outcomes

• Cure Rate at End of Therapy [Study day 10 (+/- 2 days)]: Percentage of participants with 3 or fewer unformed stools for 2 consecutive days and maintained through the end of therapy, and the subject no longer needed specific anti-Clostridium antibacterial treatment after completion of the course of study medication.

Secondary outcomes

• Recurrence [Study days 11-40]: Percentage of participants with the re-establishment of diarrhea to an extent(based on frequency of passed unformed stools) that was greater than that noted on the last day of study medication, and the demonstration of either toxin A or B or both of C. difficile, and retreatment with CDI anti-infective therapy was needed.

Other outcomes

• Global Cure [End of Study (Day 40)]: Percentage of participants who were cured (3 or fewer unformed stools for 2 days through the end of therapy, and no C. difficile therapy after study drug completion) and didn't have recurrence (re-establishment of diarrhea that was greater than on the last day of study drug, positive C. difficile toxin and retreatment with C. difficile therapy) up to Day 40.

Sex: All, ages: 16 Years to any

Inclusion Criteria:

* Males/females with CDAD
* Females must use adequate contraception
* Signed informed consent

Exclusion Criteria:

* Life-threatening CDAD
* Toxic megacolon
* Pregnant
* Concurrent use of diarrheal agents
* Participation in other trials

Participant flow

Outcome results

• Cure Rate at End of Therapy (Primary), Number, Percentage of Participants: Vancomycin 85.7 (81.3 to 89.2); Fidaxomicin 88.2 (84.0 to 91.5)
• Recurrence (Secondary), Number, Percentage of Participants: Vancomycin 25.1; Fidaxomicin 15.7 (p 0.008)
• Global Cure (Other pre specified), Number, Percentage of Participants: Vancomycin 64.2; Fidaxomicin 74.4 (p 0.007)

Adverse events

Time frame: From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.

Serious adverse events by term

83 more terms not shown.

Other adverse events by term

• Results publication: Louie TJ, Miller MA, Mullane KM, Weiss K, Lentnek A, Golan Y, Gorbach S, Sears P, Shue YK; OPT-80-003 Clinical Study Group. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med. 2011 Feb 3;364(5):422-31. doi: 10.1056/NEJMoa0910812. PMID 21288078
• Results publication: D'Agostino RB Sr, Collins SH, Pencina KM, Kean Y, Gorbach S. Risk estimation for recurrent Clostridium difficile infection based on clinical factors. Clin Infect Dis. 2014 May;58(10):1386-93. doi: 10.1093/cid/ciu107. Epub 2014 Mar 5. PMID 24599770
• Results publication: Cornely OA, Miller MA, Fantin B, Mullane K, Kean Y, Gorbach S. Resolution of Clostridium difficile-associated diarrhea in patients with cancer treated with fidaxomicin or vancomycin. J Clin Oncol. 2013 Jul 1;31(19):2493-9. doi: 10.1200/JCO.2012.45.5899. Epub 2013 May 28. PMID 23715579
• Results publication: Cornely OA, Miller MA, Louie TJ, Crook DW, Gorbach SL. Treatment of first recurrence of Clostridium difficile infection: fidaxomicin versus vancomycin. Clin Infect Dis. 2012 Aug;55 Suppl 2(Suppl 2):S154-61. doi: 10.1093/cid/cis462. PMID 22752865
• Results publication: Louie TJ, Cannon K, Byrne B, Emery J, Ward L, Eyben M, Krulicki W. Fidaxomicin preserves the intestinal microbiome during and after treatment of Clostridium difficile infection (CDI) and reduces both toxin reexpression and recurrence of CDI. Clin Infect Dis. 2012 Aug;55 Suppl 2(Suppl 2):S132-42. doi: 10.1093/cid/cis338. PMID 22752862
• Results publication: Nerandzic MM, Mullane K, Miller MA, Babakhani F, Donskey CJ. Reduced acquisition and overgrowth of vancomycin-resistant enterococci and Candida species in patients treated with fidaxomicin versus vancomycin for Clostridium difficile infection. Clin Infect Dis. 2012 Aug;55 Suppl 2(Suppl 2):S121-6. doi: 10.1093/cid/cis440. PMID 22752860
• Results publication: Figueroa I, Johnson S, Sambol SP, Goldstein EJ, Citron DM, Gerding DN. Relapse versus reinfection: recurrent Clostridium difficile infection following treatment with fidaxomicin or vancomycin. Clin Infect Dis. 2012 Aug;55 Suppl 2(Suppl 2):S104-9. doi: 10.1093/cid/cis357. PMID 22752857

• Medical Director, Study director, Merck Sharp & Dohme LLC