Effect of Additional Nebulized Amikacin in Ventilator-Associated Pneumonia Caused by Gram Negative Bacteria

The purpose of this study is to determine the cure rate from ventilator-associated pneumonia (VAP) caused by Gram negative bacteria when administering add on nebulized amikacin to intravenous antibiotics compared to intravenous antibiotics alone.

Study Overview

• Status: Completed
• Conditions: Pneumonia, Ventilator-Associated
• Intervention / Treatment: Drug: Amikacin; Drug: Placebo

Detailed Description

After inclusion, the patients are randomized into two groups: nebulized amikacin plus intravenous antibiotic(s) or nebulized placebo plus intravenous antibiotic(s). The dose of nebulized amikacin is 400 mg every 12 hours for 10 days. The patients are followed up on day 3, 7, 10, and 28 for safety and efficacy. The estimate sample size is 84 subjects base on previous study of cure rate in VAP and the authors expected that nebulized amikacin can improve cure rate in VAP subjects for 30% when compared with intravenous antibiotic(s) alone with power of 80% at level of significance 0.05.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Thailand
  • Pathumthani, Thailand, 12120
    • Thammasat University (Rangsit center)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age >/= 18 years
• On mechanical ventilator more than 7 days

• VAP diagnosis inclusion criteria:

  1. new/progressive infiltration of chest radiography
  2. 2/3 of the following: 1) fever 2) purulent sputum 3) Wbc > 12,000 cell/mm3 or < 4,000 cell/mm3
• Evidence of gram negative bacilli from sputum gram stain or previous sputum culture within 1 week

Exclusion Criteria:

• History of amikacin allergy
• GFR < 30 mL/min except dialytic patients
• Immunocompromised host: HIV CD4 < 200 cells/mm3, leukemia, lymphoma, received chemotherapy within 3 weeks, Absolute neutrophil count < 500/mm3
• Severe ARDS (P/F ratio < 100)
• Endobronchial obstruction:endobronchial mass, endobronchial stenosis
• Atelectasis
• Severe bronchospasm
• Lung abscess
• Complicated parapneumonic effusion/ Empyema
• Chest trauma
• Uncontrolled extrapulmonary infection(s)
• Received intravenous antibiotic(s) more than 48 hours
• Pregnancy/ Lactation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nebulized amikacin; Amikacin 400 mg nebulized every 12 hours plus intravenous antibiotic(s) for 10 days	Drug: Amikacin; 400 mg, nebulizer, every 12 hours, 10 days; Other Names: Amikin
Placebo Comparator: placebo; nebulized placebo every 12 hours plus intravenous antibiotic(s)for 10 days.	Drug: Placebo; placebo 4 ml, nebulizer, every 12 hours, 10 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cure rate	Cure rate = improvement/ no new infiltration of chest radiography plus 2/3 of the following: 1) No fever within 48 hours after end of the intervention 2) The reduction of secretion 3) The reduction of white blood cell	10 days after end of the intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The reduction of pathogens	quantitative sputum cultures were measured every days for 10 days or no growth of organism.	10 days after end of the intervention
mortality rate	All causes of death during the intervention	at 28 days after end of the intervention
duration of mechanical ventilation	number of days on mechanical ventilation	at 28 days after end of the intervention
duration of ICU stay	number of ICU days	at 28 days after end of the intervention
duration of hospitalization	number of days hospitalization	at 28 days after end of the intervention
Safety of intervention drug	Any adverse events were recorded	at 28 days after end of the intervention

Collaborators and Investigators

• Sponsor: Thammasat University
• Investigators: Principal Investigator: Pitchayapa Ruchiwit, MD, Thammasat University Hospital

Publications and helpful links

General Publications

• Czosnowski QA, Wood GC, Magnotti LJ, Croce MA, Swanson JM, Boucher BA, Fabian TC. Adjunctive aerosolized antibiotics for treatment of ventilator-associated pneumonia. Pharmacotherapy. 2009 Sep;29(9):1054-60. doi: 10.1592/phco.29.9.1054.
• Ghannam DE, Rodriguez GH, Raad II, Safdar A. Inhaled aminoglycosides in cancer patients with ventilator-associated Gram-negative bacterial pneumonia: safety and feasibility in the era of escalating drug resistance. Eur J Clin Microbiol Infect Dis. 2009 Mar;28(3):253-9. doi: 10.1007/s10096-008-0620-5. Epub 2008 Aug 28.

Helpful Links

• Adjunctive aerosolized antibiotics for treatment of ventilator-associated pneumonia
• Inhaled aminoglycosides in cancer patients with ventilator-associated Gram-negative bacterial pneumonia: safety and feasibility in the era of escalating drug resistance

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): April 1, 2018
• Study Completion (Actual): April 1, 2018

Study Registration Dates

• First Submitted: October 9, 2015
• First Submitted That Met QC Criteria: October 9, 2015
• First Posted (Estimate): October 12, 2015

Study Record Updates

• Last Update Posted (Actual): April 26, 2018
• Last Update Submitted That Met QC Criteria: April 24, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Cross Infection; Iatrogenic Disease; Healthcare-Associated Pneumonia; Pneumonia; Pneumonia, Ventilator-Associated; Anti-Infective Agents; Anti-Bacterial Agents; Amikacin
• Other Study ID Numbers: MTU-EC-IM-2-046/57