Efficacy
Study design and clinical end points
DIFICID was studied in adults vs vancomycin in two phase 3 Clostridioides (formerly Clostridium) difficile–associated diarrhea (CDAD) trials.
Study design
- Two randomized, double-blind, noninferiority trials
Patients
- 1,105 patients ≥18 years of age
- Diagnosis of C. difficile–associated diarrhea as defined by:
- >3 unformed bowel movements (UBM) (or >200 mL of unformed stool for subjects having rectal collection devices) in the 24 hours before randomization
- Presence of C. difficile toxin A or B in stool sample within 48 hours of randomization
- No more than 24 hours of pretreatment with vancomycin or metronidazole
- No more than one prior C. difficile–associated diarrhea episode in past 3 months
- 37% of patients had severe C. difficile–associated diarrhea (defined as ≥10 UBM per day or WBC ≥15,000/mm3)
- 16% of patients studied had a prior episode of CDAD within the last 3 months
- 50% of patients were ≥65 years of age and 31% were ≥75 years of age
- Exclusion criteria : Life-threatening/fulminant infection, hypotension, septic shock, peritoneal signs, significant dehydration, or toxic megacolon.
Clinical end points
- Clinical response was defined as improvement in diarrhea or other symptoms, such that further C. difficile–associated diarrhea treatment was not needed.
- Sustained response was defined as clinical response at the end of treatment and survival without proven or suspected C. difficile–associated diarrhea recurrence through 25 days beyond the end of treatment.
Definitions
CDAD = Clostridioides difficile–associated diarrhea
UBM = unformed bowel movements
WBC = white blood cell