Inhaled amikacin adjunctive to standard-of-care intravenous antibiotic therapy was not associated with improvements in survival in mechanically ventilated patients with Gram-negative pneumonia, according to the results of a phase 3 study published in the Lancet: Infectious Diseases.
The study consisted of 2 clinical trials (INHALE 1 and INHALE 2; ClinicalTrials.gov Identifiers: NCT01799993 and NCT00805168, respectively) that were performed in 153 different hospital intensive care units across 25 countries. Researchers enrolled patients with pneumonia caused by or demonstrating 2 risk factors for a Gram-negative, multidrug-resistant pathogen. All patients were intubated and mechanically ventilated and presented with a modified Clinical Pulmonary Infection Score of ≥6.
After stratifying patients by region and disease severity, the researchers randomly assigned patients to either aerosolized 400 mg amikacin (n=255) or saline aerosolized placebo (n=253). Treatments were administered every 12 hours for 10 days alongside standard-of-care intravenous antibiotics. Survival at days 28 to 32 among patients who received ≥1 dose of the study drug was the primary end point. In addition, researchers assessed and compared safety outcomes in the 2 treatment groups.
Although the primary end point was not met, the investigators found no between-group difference between the amikacin and placebo groups in terms of survival (75% vs 77%, respectively; odds ratio [OR], 0.841; 95% CI, 0.554-1.277; P =.43). In the safety population, a prespecified supporting analysis found no difference between the groups that survived until the late follow-up visit (OR, 0.989; 95% CI, 0.694-1.408; P =.95). In addition, a similar proportion of patients in both groups experienced a treatment-emergent adverse event or serious treatment-emergent adverse event. A cumulative all-cause mortality analysis found that deaths occurred at similar rates in both groups.
A limitation of the study included the variability in the standard-of-care regimens used at each center.
On the basis of their findings, the INHALE investigators wrote that there is no support for the use of inhaled amikacin adjunctive to standard-of-care intravenous therapy in patients receiving mechanical ventilation who have Gram-negative pneumonia.
Disclosure: This clinical trial was supported by Bayer AG. Please see the original reference for a full list of authors’ disclosures.
Niederman MS, Alder J, Bassetti M, et al. Inhaled amikacin adjunctive to intravenous standard-of-care antibiotics in mechanically ventilated patients with Gram-negative pneumonia (INHALE): a double-blind, randomised, placebo-controlled, phase 3, superiority trial [published online December 19, 2019]. Lancet Infect Dis. doi:10.1016/S1473-3099(19)30574-2