TY - JOUR
T1 - A Randomized Trial of the Amikacin Fosfomycin Inhalation System for the Adjunctive Therapy of Gram-Negative Ventilator-Associated Pneumonia
T2 - IASIS Trial
AU - Kollef, Marin H.
AU - Ricard, Jean Damien
AU - Roux, Damien
AU - Francois, Bruno
AU - Ischaki, Eleni
AU - Rozgonyi, Zsolt
AU - Boulain, Thierry
AU - Ivanyi, Zsolt
AU - János, Gál
AU - Garot, Denis
AU - Koura, Firas
AU - Zakynthinos, Epaminondas
AU - Dimopoulos, George
AU - Torres, Antonio
AU - Danker, Wayne
AU - Montgomery, A. Bruce
N1 - Publisher Copyright:
© 2016 American College of Chest Physicians
PY - 2017/6
Y1 - 2017/6
N2 - Background Clinical failures in ventilator-associated pneumonia (VAP) caused by gram-negative bacteria are common and associated with substantial morbidity, mortality, and resource utilization. Methods We assessed the safety and efficacy of the amikacin fosfomycin inhalation system (AFIS) for the treatment of gram-negative bacterial VAP in a randomized double-blind, placebo-controlled, parallel group, phase 2 study between May 2013 and March 2016. We compared standard of care in each arm plus 300 mg amikacin/120 mg fosfomycin or placebo (saline), delivered by aerosol twice daily for 10 days (or to extubation if < 10 days) via the investigational eFlow Inline System (PARI GmbH). The primary efficacy end point was change from baseline in the Clinical Pulmonary Infection Score (CPIS) during the randomized course of AFIS/placebo, using the subset of patients with microbiologically proven baseline infections with gram-negative bacteria. Results There were 143 patients randomized: 71 to the AFIS group, and 72 to the placebo group. Comparison of CPIS change from baseline between treatment groups was not different (P = .70). The secondary hierarchical end point of no mortality and clinical cure at day 14 or earlier was also not significant (P = .68) nor was the hierarchical end point of no mortality and ventilator-free days (P = .06). The number of deaths in the AFIS group was 17 (24%) and 12 (17%) in the placebo group (P = .32). The AFIS group had significantly fewer positive tracheal cultures on days 3 and 7 than placebo. Conclusions In this trial of adjunctive aerosol therapy compared with standard of care IV antibiotics in patients with gram-negative VAP, the AFIS was ineffective in improving clinical outcomes despite reducing bacterial burden. Trial Registry ClinicalTrials.gov; No.: NCT01969799; URL: www.clinicaltrials.gov
AB - Background Clinical failures in ventilator-associated pneumonia (VAP) caused by gram-negative bacteria are common and associated with substantial morbidity, mortality, and resource utilization. Methods We assessed the safety and efficacy of the amikacin fosfomycin inhalation system (AFIS) for the treatment of gram-negative bacterial VAP in a randomized double-blind, placebo-controlled, parallel group, phase 2 study between May 2013 and March 2016. We compared standard of care in each arm plus 300 mg amikacin/120 mg fosfomycin or placebo (saline), delivered by aerosol twice daily for 10 days (or to extubation if < 10 days) via the investigational eFlow Inline System (PARI GmbH). The primary efficacy end point was change from baseline in the Clinical Pulmonary Infection Score (CPIS) during the randomized course of AFIS/placebo, using the subset of patients with microbiologically proven baseline infections with gram-negative bacteria. Results There were 143 patients randomized: 71 to the AFIS group, and 72 to the placebo group. Comparison of CPIS change from baseline between treatment groups was not different (P = .70). The secondary hierarchical end point of no mortality and clinical cure at day 14 or earlier was also not significant (P = .68) nor was the hierarchical end point of no mortality and ventilator-free days (P = .06). The number of deaths in the AFIS group was 17 (24%) and 12 (17%) in the placebo group (P = .32). The AFIS group had significantly fewer positive tracheal cultures on days 3 and 7 than placebo. Conclusions In this trial of adjunctive aerosol therapy compared with standard of care IV antibiotics in patients with gram-negative VAP, the AFIS was ineffective in improving clinical outcomes despite reducing bacterial burden. Trial Registry ClinicalTrials.gov; No.: NCT01969799; URL: www.clinicaltrials.gov
KW - aerosols
KW - antibiotics
KW - pneumonia
UR - http://www.scopus.com/inward/record.url?scp=85020918525&partnerID=8YFLogxK
U2 - 10.1016/j.chest.2016.11.026
DO - 10.1016/j.chest.2016.11.026
M3 - Article
C2 - 27890714
AN - SCOPUS:85020918525
SN - 0012-3692
VL - 151
SP - 1239
EP - 1246
JO - CHEST
JF - CHEST
IS - 6
ER -