MK-7655A-016
Trial question
Is imipenem/cilastatin/relebactam noninferior to piperacillin/tazobactam in critically ill patients with hospital-acquired or ventilator-associated bacterial pneumonia?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
27.0% female
73.0% male
N = 270
270 patients (72 female, 198 male).
Inclusion criteria: critically ill adult patients with hospital-acquired or ventilator-associated bacterial pneumonia requiring intravenous antibiotics.
Key exclusion criteria: Gram-positive cocci at baseline; community-acquired pneumonia or pneumonia caused by Mycoplasma, Chlamydia, or Legionella species, or of viral, fungal, or parasitic etiology; carcinoid tumor or carcinoid syndrome; active immunosuppression.
Interventions
N=134 imipenem/cilastatin/relebactam (500/250 mg IV administered every 6 hours for 7-14 days).
N=136 piperacillin/tazobactam (4,000/500 mg IV administered every 6 hours for 7-14 days).
Primary outcome
All-cause mortality at day 28
11.2%
5.9%
11.2 %
8.4 %
5.6 %
2.8 %
0.0 %
Imipenem/cilastatin/relebactam
Piperacillin/tazobactam
Difference not exceeding
non-inferiority
margin ✓
Difference not exceeding non-inferiority margin in all-cause mortality at day 28 (11.2% vs. 5.9%; AD 5.2%, 95% CI -1.5 to 12.4).
Secondary outcomes
No significant difference in favorable clinical response at the end of treatment (71.6% vs. 68.4%; AD 3.4%, 95% CI -7.6 to 14.3).
No significant difference in favorable microbiological response at the end of treatment (57.5% vs. 60.3%; ARD -2.4, 95% CI -17.8 to 13.1).
No significant difference in favorable microbiological response at the end of treatment in microbiologically evaluable population (71.9% vs. 74.5%; ARD -3.1, 95% CI -19.8 to 14.4).
Safety outcomes
No significant difference in adverse events.
Conclusion
In critically ill adult patients with hospital-acquired or ventilator-associated bacterial pneumonia requiring intravenous antibiotics, imipenem/cilastatin/relebactam was noninferior to piperacillin/tazobactam with respect to all-cause mortality at day 28.
Reference
Junjie Li, Feng Wei, Peng Xiang et al. A phase III randomized controlled non-inferiority trial to study the efficacy and safety of imipenem / cilastatin / relebactam (IMI / REL) versus piperacillin / tazobactam (PIP / TAZ) in patients with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP). Int J Infect Dis. 2024 Dec 12:107357. Online ahead of print.
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