OBJECTIVES: Symptoms associated with recurrent Clostridioides difficile infection (rCDI) are debilitating, often leading to long-term effects on health-related quality-of-life (HRQOL). In ECOSPOR-III, a Phase 3 trial, oral SER-109 was superior to placebo in reducing risk of rCDI. This study sought to establish the validity and responsiveness of a CDI-specific questionnaire (Cdiff32) in patients with rCDI regardless of treatment arm.

METHODS: Adult outpatients with rCDI (≥3 episodes in 12 months) were screened at 56 US/Canadian sites. After completing standard-of-care antibiotics, subjects were randomized 1:1 to SER-109 or placebo. The primary endpoint was rCDI (toxin+ diarrhea requiring treatment) at 8 weeks. Exploratory endpoints included the EQ-5D-5L and Cdiff32, a 32-item questionnaire measuring HRQOL overall and across mental, physical, and social subscales, at baseline, 1 and 8 weeks. The Cdiff32 was evaluated for dimensionality, item performance, internal reliability, and convergent validity. To assess known-groups validity, Cdiff32 scores were compared across recurrent versus non-recurrent patients at week 1. Internal responsiveness was evaluated in non-recurrent patients by 8 weeks using a paired t-test.

RESULTS: Cdiff32 was completed at baseline by 182 patients (mean age 65.5±16.5, 59.9% female). Confirmatory factor analysis identified 3 domains with good item fit. High internal reliability was demonstrated (Cronbach’s alpha=0.94 with all subscales>0.80). Convergent validity was evidenced by significant correlations between Cdiff32 subscales and EQ-5D index (r range: 0.27-0.36, p<0.001). Cdiff32 differentiated recurrent (n=44) from non-recurrent (n=130) patients at week 1 (effect sizes: 0.38-0.43; p<0.05 for all), and was responsive to change, with significant improvement from baseline to week 8 in 134 non-recurrent patients (effect sizes: 0.75-1.02; p<0.001 for all).

CONCLUSIONS: Cdiff32 demonstrated excellent validity and reliability in patients with rCDI, with significant improvement in patients without recurrence by 8 weeks. These findings highlight the negative impact of rCDI on HRQOL and justify the utilization of the Cdiff32 in patients with rCDI.