3 Key Takeaways
Plain English Summary- 01Core Finding
Patients aged 18 years or older with HABP and VABP caused by clinically documented or suspected Gram-negative pathogens were assigned by stratified block randomisation at a 2:1 ratio to receive 1·25 g imipenem-cilastatin-funobactam or 1·25 g imipenem-cilastatin-relebactam via 30-min intravenous infusion every 6 h for 7-14 days with the dose adjusted according to renal function.
- 02Study Evidence
Tested in a randomized controlled trial (534 patients) at the Phase III stage.
- 03Practical Meaning
Large Phase III clinical evidence — long-term durability and rare subgroup effects remain under study.
What This Means for You
Imipenem-cilastatin-funobactam is statistically non-inferior to imipenem-cilastatin-relebactam for 14-day all-cause mortality in patients with HABP and VABP with a favourable safety profile.
The Discovery
New antibiotics are urgently needed for hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP). We aimed to compare the efficacy (real-world effectiveness in the trial) and safety of imipenem-cilastatin-funobactam with imipenem-cilastatin-relebactam in patients with HABP and VABP.
The Phase 3, multinational, double-blind, non-inferiority, randomised controlled trial was conducted in 62 hospitals (58 in China, three in the USA, and one in Spain). Patients aged 18 years or older with HABP and VABP caused by clinically documented or suspected Gram-negative pathogens were assigned by stratified block randomisation at a 2:1 ratio to receive 1·25 g imipenem-cilastatin-funobactam or 1·25 g imipenem-cilastatin-relebactam via 30-min intravenous infusion every 6 h for 7-14 days with the dose adjusted according to renal function. Patients with previous use of prohibited antibiotics or conditions that could interfere with efficacy (real-world effectiveness in the trial) assessment were excluded. Masking was maintained for investigators and patients; emergency unmasking followed standard operating procedures. Missing mortality data were considered as survival in the primary endpoint analysis. The primary outcome was 14-day all-cause mortality in the modified intention-to-treat (mITT) population, with a 10% non-inferiority margin (two-sided 95% CI). This trial is registered with ClinicalTrials.gov (NCT05204563).
Between Oct 29, 2022, and Sept 29, 2024, 534 patients were screened, 450 were randomly assigned, and 449 were included in safety populations. The mITT population also included 449 patients (mean age was 60·8 years [SD 13·9]; 313 [7a clinically meaningful level] of 449 were male). In the mITT population, 14-day all-cause mortality was 3·a clinically meaningful level (nine of 299) for imipenem-cilastatin-funobactam versus 2·7% (four of 150) for imipenem-cilastatin-relebactam (difference 0·2%; 95% CI -3·5% to 4·a clinically meaningful level). Grade 3 or higher treatment-related adverse events occurred in 22 (7%) of 299 patients in the imipenem-cilastatin-funobactam and 16 (11%) of 150 patients in the imipenem-cilastatin-relebactam group. No drug-related deaths were reported.
How It Works, Simply
This infectious disease research focuses on gut bacteria. Researchers evaluated it using a randomized controlled trial (534 patients) at the Phase III stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
Patients aged 18 years or older with HABP and VABP caused by clinically documented or suspected Gram-negative pathogens were assigned by stratified block randomisation at a 2:1 ratio to receive 1·25 g imipenem-cilastatin-funobactam or 1·25 g imipenem-cilastatin-relebactam via 30-min intravenous infusion every 6 h for 7-14 days with the dose adjusted according to renal function.
- 02Study Evidence
Tested in a randomized controlled trial (534 patients) at the Phase III stage.
- 03Practical Meaning
Large Phase III clinical evidence — long-term durability and rare subgroup effects remain under study.
Key Numbers
Biological Mechanism & Study Design
Study Design & Cohort
Randomized controlled trial
Randomized controlled trial (534 patients) · Phase III
Biological Pathway & Modality
Gut bacteria
Intervention: Imipenem-cilastatin-funobactam versus imipenem-cilastatin-relebactam in patients
Experimental Findings & Endpoints
New antibiotics are urgently needed for hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP).
We aimed to compare the efficacy and safety of imipenem-cilastatin-funobactam with imipenem-cilastatin-relebactam in patients with HABP and VABP.
The Phase 3, multinational, double-blind, non-inferiority, randomised controlled trial was conducted in 62 hospitals (58 in China, three in the USA, and one in Spain). Patients aged 18 years or older with HABP and VABP caused by clinically documented or suspected Gram-negative pathogens were assigned by stratified block randomisation at a 2:1 ratio to receive 1·25 g imipenem-cilastatin-funobactam or 1·25 g imipenem-cilastatin-relebactam via 30-min intravenous infusion every 6 h for 7-14 days with the dose adjusted according to renal function.
Patients with previous use of prohibited antibiotics or conditions that could interfere with efficacy assessment were excluded. Masking was maintained for investigators and patients; emergency unmasking followed standard operating procedures.
Missing mortality data were considered as survival in the primary endpoint analysis. The primary outcome was 14-day all-cause mortality in the modified intention-to-treat (mITT) population, with a 10% non-inferiority margin (two-sided 95% CI).
This trial is registered with ClinicalTrials.gov (NCT05204563).
Between Oct 29, 2022, and Sept 29, 2024, 534 patients were screened, 450 were randomly assigned, and 449 were included in safety populations. The mITT population also included 449 patients (mean age was 60·8 years [SD 13·9]; 313 [7a clinically meaningful level] of 449 were male).
In the mITT population, 14-day all-cause mortality was 3·a clinically meaningful level (nine of 299) for imipenem-cilastatin-funobactam versus 2·7% (four of 150) for imipenem-cilastatin-relebactam (difference 0·2%; 95% CI -3·5% to 4·a clinically meaningful level). Grade 3 or higher treatment-related adverse events occurred in 22 (7%) of 299 patients in the imipenem-cilastatin-funobactam and 16 (11%) of 150 patients in the imipenem-cilastatin-relebactam group.
No drug-related deaths were reported.
Clinical Translation & Practice Context
Imipenem-cilastatin-funobactam is statistically non-inferior to imipenem-cilastatin-relebactam for 14-day all-cause mortality in patients with HABP and VABP with a favourable safety profile.
The Bottom Line · Clinical Pearl
“Imipenem-cilastatin-funobactam is statistically non-inferior to imipenem-cilastatin-relebactam for 14-day all-cause mortality in patients with HABP and VABP with a favourable safety profile.”
Published in The Lancet Infectious Diseases · Current Stage: Phase III