Imipenem-cilastatin-funobactam versus imipenem-cilastatin-relebactam in patients with hospital-acquired bacterial pneumonia or ventilator-associated bacterial pneumonia: a phase 3, double-blind, non-inferiority randomised trial

Why clinicians should know about it

• Picked for Pulmonary and Respiratory Medicine (paper of the day, 6 November 2026): Imipenem‑funobactam vs relebactam in HABP/VABP

Abstract

BACKGROUND: 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. METHODS: 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). FINDINGS: 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 [70%] of 449 were male). In the mITT population, 14-day all-cause mortality was 3·0% (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 4·0%). 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. INTERPRETATION: 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. FUNDING: Evopoint Biosciences. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Abstract as published, via PubMed.