CLOVER
Trial question
What is the role of detoxified toxin A/B vaccine in adults who are at increased risk of C. difficile infection?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
51.0% female
49.0% male
N = 17440
17440 patients (8973 female, 8467 male).
Inclusion criteria: adults aged ≥ 50 years who are at increased risk of C. difficile infection.
Key exclusion criteria: ≥ 1 confirmed prior C. difficile infection episode; prior C. difficile vaccination or monoclonal antibody therapy; known infection; any condition/treatment resulting in frequent diarrhea; unable to respond to vaccination.
Interventions
N=8722 detoxified toxin A/B vaccine (PF-06425090 200 mcg total toxoid in the deltoid at 0, 1, and 6 months).
N=8718 placebo (0.9% saline in the deltoid at 0, 1, and 6 months).
Primary outcome
Rate of first Clostridioides difficile infection episode ≥ 14 days after dose 3
0.22%
0.32%
0.3 %
0.2 %
0.2 %
0.1 %
0.0 %
Detoxified toxin A/B
vaccine
Placebo
No significant
difference ↔
No significant difference in the rate of first C. difficile infection episode ≥ 14 days after dose 3 (0.22% vs. 0.32%; VE 31, 96% CI -38.7 to 66.6).
Secondary outcomes
No significant difference in the rate of first C. difficile infection episode ≥ 14 days after dose 2 (0.31% vs. 0.43%; VE 28.6, 96% CI -28.4 to 61).
Significant decrease in median C. difficile infection duration (1 day vs. 4 day; AD -3 day, 95% CI -5.53 to -0.47).
Significant increase in C. difficile infection-related medical attention (0% vs. 0.14%; VE 100, 95% CI 59.6 to 100).
Safety outcomes
No significant difference in adverse events.
Conclusion
In adults aged ≥ 50 years who are at increased risk of C. difficile infection, detoxified toxin A/B vaccine was not superior to placebo with respect to the rate of first C. difficile infection episode ≥ 14 days after dose 3.
Reference
Curtis J Donskey, Erik R Dubberke, Nicola P Klein et al. CLOVER (CLOstridium difficile Vaccine Efficacy tRial) Study: A Phase 3, Randomized Trial Investigating the Efficacy and Safety of a Detoxified Toxin A / B Vaccine in Adults 50 Years and Older at Increased Risk of Clostridioides difficile Infection. Clin Infect Dis. 2024 Dec 17;79(6):1503-1511.
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