Methods: This double blind study randomised 100 patients 1:1 to 10 days RDZ 200 mg BID or vancomycin (VAN) 125 mg QID treatment. Subjects were enrolled with CDI symptoms and a positive diagnostic result (FT or TS). Baseline (BL) stool samples were assessed for the presence of FT. All subjects entered the intent to treat (ITT) population; those subjects positive for FT entered a modified ITT (mITT), the primary analysis population. Primary endpoint was sustained clinical response (SCR) defined as cure at end of therapy and no rCDI for the next 30 days. rCDI was defined as CDI symptoms, a positive diagnostic test and need for therapy; a sensitivity analysis considered positive FT rCDI cases. BL faecal concentrations of lactoferrin and calprotectin were determined by enzyme immunoassay.
Results: Of 100 subjects enrolled, 69 (36 RDZ: 33 VAN) were FT positive at BL. RDZ compared with VAN recipients had improved SCR rates via reduced rCDI. Absolute differences in SCR between RDZ and VAN (prespecified 90% CI) for MITT (FT positive) and ITT subjects were 24.3% (3.1, 39.1) and 14.0% (-1.8, 28.8), respectively. Absolute SCR differences between the MITT and ITT subjects from the sensitivity analysis were 26.2% (4.6, 40.6) and 14.3% (-1.7, 29.1). Median BL calprotectin and lactoferrin levels (µg/mL) were significantly higher for FT positive subjects at 1,002 and 87, than for FT negative subjects at 53 and 4, respectively.
Conclusion: RDZ showed improved SCR in comparison with VAN. Treatment differences were greater in MITT subjects. Lower SCR improvement in RDZ ITT subjects is likely due to enrolment of some colonised rather than infected subjects; this explanation is supported by higher calprotectin and lactoferrin levels in FT positive samples. These data demonstrate the importance of FT testing in-line with CDI guideline recommendations.
M. Wilcox, Summit Therapeutics: Consultant , Research Contractor and Scientific Advisor , Consulting fee , Research grant and Research support .