Clinical Trial: Aerosolized Antibiotics in the Treatment of Ventilator Associated Pneumonia

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Aerosolized Antibiotics in the Treatment of Ventilator Associated Pneumonia: A Pilot Study

Brief Summary: The purpose of this study is to determine if administering inhaled antibiotics directly into the lungs in conjunction with intravenous (IV) antibiotics leads to better outcomes and decreased recurrence of ventilator associated pneumonia (VAP) when compared to IV antibiotics alone.

Detailed Summary:

Ventilator associated pneumonia (VAP) remains a serious problem in critically ill patients with an incidence of 8-28% and mortality ranging from 24-57%. A landmark study comparing eight days versus fifteen days of antibiotic therapy reported a pulmonary infection recurrence rate of 26-29%. Costs associated with VAP can reach up to $40,000 per occurrence.

Aerosolized antibiotics have been used to treat ailments such as cystic fibrosis and bronchiectasis. Previous research indicates that aerosolized antibiotics attain a 200 fold greater concentration in the lung than in the blood, and that sputum trough levels remain 20 fold greater than that of acceptable serum antibiotic troughs. Additionally, aerosolized antibiotics are considered safe (without increased risk of bacterial resistance) with better treatment success when compared to controls (OR 2.75, 95% CI 1.06-7.17), although no mortality benefit has been identified. Some studies have shown reduced systemic toxicity when using aerosolized antibiotics while others have shown no difference. Aerosolized tobramycin prevents pseudomonas infections in patients with Cystic Fibrosis. Furthermore aerosolized antibiotics improve pulmonary function in these patients, including Forced Expiratory Volume in 1 second (FEV1), and decrease the need for hospitalization. Lung transplant patients and patients with Human Immunodeficiency Virus (HIV) also benefit from aerosolized fungal prophylaxis and treatment. The benefit has been less clear in patients with non-Cystic Fibrosis bronchiectasis, and although some studies show benefits to aerosolized antibiotics in preventing and treating nosocomial pneumonias, no large prospective randomized trials have been performed to confirm the benefit or to change practice recommendations.

Antimicrobials must reach the site of infection, bind the target
Sponsor: Wright State University

Current Primary Outcome:

  • Recurrence of pneumonia [ Time Frame: 9-21 days after initiating antibiotic therapy ]
    Recurrence after a second bronchoalveolar lavage (BAL) reveals at least one bacterial species growing at concentrations of greater than 10 to the fourth power organisms during the time period of 9-21 days after initiating therapy.
  • Persistence of pneumonia [ Time Frame: 8 days after initiation of therapy for pneumonia ]
    Persistence will be defined as the need to continue antibiotic therapy for greater than 7 days.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Ventilator-free days [ Time Frame: 28 days ]
    number of days not on vent in first 28 days after randomization
  • Intensive Care Unit (ICU) -free days in 28 days [ Time Frame: 28 days ]
    number of days not in ICU after initiation of therapy
  • 28-day ICU mortality [ Time Frame: 28 days ]
    number of patients treated in each arm who die in ICU within 28 days of initiation of therapy
  • 28-day overall mortality [ Time Frame: 28 days ]
    number of patients treated in each arm who die in the hospital within 28 days of initiation of therapy
  • renal insufficiency [ Time Frame: 28 days ]
    patients who develop acute kidney injury after randomization
  • multiple organ dysfunction score at randomization and on day 7 of aerosolized antibiotics/placebo treatment [ Time Frame: 7 days ]
    multiple organ dysfunction score calculated at randomization and on day 7 of treatment
  • emergence of resistant organisms [ Time Frame: 28 days ]
    patients with failure of therapy or persistence who grow resistant organisms after being treated initially
  • number of antibiotic days [ Time Frame: 28 days ]
    total days antibiotics administered for pneumonia after randomization


Original Secondary Outcome: Same as current

Information By: Wright State University

Dates:
Date Received: April 30, 2015
Date Started: June 2015
Date Completion: December 2017
Last Updated: September 23, 2016
Last Verified: September 2016