Randomized double-blind clinical trial evaluating the effectiveness and safety of secondary prophylaxis with oral vancomycin versus placebo in the prevention of recurrence of clostridioides difficile infection in patients receiving systemic antibiotic therapy (PREVAN trial)

Abstract Background Recurrence of Clostridioides difficile infection (CDI) is frequent, particularly in patients requiring subsequent systemic antibiotics. Observational studies suggest that secondary prophylaxis with oral vancomycin (SPV) may reduce recurrence risk, but randomized evidence remains scarce. Methods PREVAN (NCT05320068) was a phase III, double-blind, placebo-controlled randomized clinical trial conducted at a tertiary hospital in Spain. Adults with documented CDI within the previous 180 days who required hospitalization and systemic antibiotics were randomized (2:1) to receive oral vancomycin (125 mg every 6 h) or placebo for 10 days, stratified by type of index CDI episode. Primary endpoints were CDI recurrence within 60 days after end of therapy and CDI recurrence-free survival. Results Twenty-one patients were enrolled (14 SPV; 7 placebo). Mean age was 73.5 years and 76.7% had malignancy and/or immunosuppression. CDI recurrence occurred in 5 patients (23.8%): 2 (14.3%) in the SPV group and 3 (42.9%) in the placebo group (P = 0.30). CDI recurrence-free survival at 60 days was 83% (95% CI 48–95) with SPV versus 42% (95% CI 6–77) with placebo (log-rank P = 0.09). No treatment-related serious adverse events were observed; one mild diarrhoeal event occurred in a placebo-treated patient. Conclusions In high-risk patients with recent CDI requiring systemic antibiotics, SPV appeared safe and was associated with a clinically relevant reduction in recurrence, although the trial was underpowered. These findings support further adequately powered randomized studies to define the role of SPV in preventing CDI recurrence.