Phase 2/3, Open-label, Randomized, Active-controlled Clinical Trial Evaluating the Safety and Efficacy of Imipenem/Cilastatin/Relebactam in Pediatric Patients From Birth to Less Than 18 Years With Gram-negative Bacterial Infections.
John S Bradley, Carmelle T Norice, Emmanuel Roilides et al.
✦ AI-curated · Sources linked
In 30 seconds
This multinational, open-label, randomized, active-controlled phase 2/3 estimation trial evaluated imipenem/cilastatin/relebactam (IMI/REL) in children from birth to under 18 years with hospital-acquired or ventilator-associated pneumonia, complicated intra-abdominal infection, or complicated urinary tract infection. Eighty-six participants received IMI/REL and 29 received standard-of-care antibiotics. Adverse events occurred in 67.1% versus 50.0%, respectively (treatment difference: 17.1% [95% confidence interval: -3.5, 37.2]). At end of therapy, clinical and microbiologic responses were generally comparable between groups; no deaths occurred.
Key findings
- Adverse events were reported in 67.1% with IMI/REL and 50.0% with active control (treatment difference: 17.1% [95% confidence interval: -3.5, 37.2]).
- Three IMI/REL participants and no active-control participants discontinued IV therapy because of adverse events.
- At end of therapy, clinical response was 78.8% versus 75.0%, and microbiologic response was 95.6% versus 90.9%, with IMI/REL and active control, respectively.
- No mortality occurred in either treatment group.
Why it matters
Prospective pediatric safety and efficacy data for broad-spectrum Gram-negative therapy are needed, including in neonates. This trial provides comparative observations across several serious infection types and age groups. The response findings were generally similar to standard-of-care therapy, while the numerically higher adverse-event frequency with IMI/REL underscores the importance of considering tolerability alongside treatment outcomes.
What to keep in mind
The trial was an estimation study without hypothesis testing, and the randomized groups were unequal in size; the findings therefore do not establish comparative efficacy or safety.