0
Original Research |

A randomized trial of the amikacin fosfomycin inhalation system for the adjunctive therapy of Gram-negative ventilator-associated pneumonia: IASIS Trial

Marin H. Kollef, MD; Jean-Damien Ricard, MD; Damien Roux, MD; Bruno Francois, MD; Eleni Ischaki, MD; Zsolt Rozgonyi, MD; Thierry Boulain, MD; Zsolt Ivanyi, MD; Gál János, MD; Denis Garot, MD; Firas Koura, MD; Epaminondas Zakynthinos, MD; George Dimopoulos, MD; Antonio Torres, MD; Wayne Danker, MD; A. Bruce Montgomery, MD
Author and Funding Information

Conflict of Interest Disclosures: A. Bruce Montgomery is the chief executive officer of Cardeas Pharma. Dr. Kollef’s effort was supported by the Barnes-Jewish Hospital Foundation. The remaining authors have no conflicts to report.

ClinicalTrials.gov Identifier: NCT01969799

1Washington University School of Medicine, Saint Louis, Missouri, USA

2Inserm, IAME, UMR 1137, Univ Paris Diderot, Sorbonne Paris Cité, Paris, France - AP-HP, Hopital Louis Mourier, Service de Reanimation Medico-Chirurgicale, Colombes

3Inserm CIC-1435 & UMR 1092, Réanimation Polyvalente, CHU, Limoges, France

4General Hospital of Athens “Evangelismos”, Athens, Greece

5Orszagos Koranyi TBC es Pulmonologiai Intezet, Budapest, Hungary

6Hôpital de La Source, Orléans France

7Semmelweis University, Budapest, Hungary

8CHRU Bretonneau, Tours, France

9Kentucky Lung Clinic Hazard, Kentucky, USA

10University General Hospital of Larisa, Larisa Greece

11National and Kapodistrian University of Athens, Greece

12Department of Pulmonology, Hospital Clinic, IDIBAPS, CIBERES, University of Barcelona, Spain

13Wayne Danker, Parexel Corp. Research Triangle Park, North Carolina, USA

14Cardeas Pharma Corp., Seattle, Washington, USA

Corresponding Author: Marin H. Kollef, MD Division of Pulmonary and Critical Care Medicine Washington University School of Medicine 4523 Clayton Avenue, Campus Box 8052 St. Louis, MO 63110.


Copyright 2016, . All Rights Reserved.


Chest. 2016. doi:10.1016/j.chest.2016.11.026
Text Size: A A A
Published online

Abstract

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, Germany). The primary efficacy endpoint 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  143 patients were randomized, 71 to AFIS, 72 to placebo. Comparison of CPIS change from baseline between treatment groups was not different (P=0.70). The secondary hierarchical endpoint of no mortality and clinical cure at Day 14 or earlier was also not significant (P=0.68) nor the hierarchical endpoint of no mortality and ventilator free days (P=0.06). Mortality was 17 (24%) in AFIS, 12 (17%) in placebo P=0.32. The AFIS group had significantly fewer positive tracheal cultures on Days 3 and 7 compared to placebo.

Conclusions  In this trial of adjunctive aerosol therapy compared to standard of care intravenous antibiotics in patients with Gram-negative VAP, AFIS was ineffective in improving clinical outcomes despite reducing bacterial burden.


Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Figures

Tables

References

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543