DISRUPT
Trial question
What is the role of exebacase in addition to antibiotics in patients with S. aureus bloodstream infection and right-sided infective endocarditis?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
37.0% female
63.0% male
N = 250
250 patients (92 female, 158 male).
Inclusion criteria: patients with S. aureus bloodstream infection and right-sided infective endocarditis.
Key exclusion criteria: known or suspected left-sided infective endocarditis or uncomplicated bloodstream infections; prosthetic valve or cardiac valve support ring; polymicrobial bloodstream infection.
Interventions
N=165 exebacase plus antibiotics (a single dose of IV exebacase plus standard-of-care antibiotics).
N=85 antibiotics alone (placebo plus standard-of-care antibiotics).
Primary outcome
Clinical response at day 14 in methicillin-resistant Staphylococcus aureus population
50%
60.6%
60.6 %
45.5 %
30.3 %
15.2 %
0.0 %
Exebacase plus
antibiotics
Antibiotics
alone
No significant
difference ↔
No significant difference in clinical response at day 14 in MRSA population (50% vs. 60.6%; ARD 10.6, 95% CI -12.4 to 33.6).
Secondary outcomes
No significant difference in clinical response at day 14 in overall population (59.4% vs. 71.8%; ARD 12.4, 95% CI -0.7 to 25.4).
No significant difference in survival at day 30 in MRSA population (79.7% vs. 90.9%; ARD 11.2, 95% CI -3.74 to 26.14).
Safety outcomes
No significant differences in treatment-emergent adverse events through day 60, death through day 60.
Conclusion
In patients with S. aureus bloodstream infection and right-sided infective endocarditis, exebacase plus antibiotics were not superior to antibiotics alone with respect to clinical response at day 14 in MRSA population.
Reference
Vance G Fowler Jr, Anita F Das, Joy Lipka-Diamond et al. Exebacase in Addition to Standard-of-Care Antibiotics for Staphylococcus aureus Bloodstream Infections and Right-Sided Infective Endocarditis: A Phase 3, Superiority-Design, Placebo-Controlled, Randomized Clinical Trial (DISRUPT). Clin Infect Dis. 2024 Jun 14;78(6):1473-1481.
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