Addition of Tobramycin Inhalation in the Treatment of Ventilator Associated Pneumonia

Erasmus Medical Center80 enrolled

Overview

This study evaluates the addition of tobramycin inhalation treatment to standard intravenous therapy in the treatment of ventilator associated pneumonia.

Rationale: Approximately 9-27% of mechanically ventilated patients in the intensive care unit (ICU) develop ventilator-associated pneumonia (VAP). Patients in whom VAP develops have a higher mortality rate up to 50%, stay longer in the intensive care unit (ICU), and require more resources than those without the disease. Despite the availability of modern ICU care and modern antibiotics, the overall clinical cure rate after 72 hours of antibiotic treatment for VAP is only 40%. The cure rate for Pseudomonas aeruginosa is even lower. It is unclear why VAP cure rates are so low. The ATS guidelines recommend IV antibiotic treatment (IV AB), especially directed against gram-negative microorganisms. However, the relatively poor response rates seen with intravenous therapy of VAP and the emergence of MDR organisms makes new treatment options desirable. The ATS/IDSA VAP guidelines recommend that "adjunctive therapy with an inhaled aminoglycoside or polymyxin (colistin) for MDR Gram-negative pneumonia should be considered, especially in patients who are not improving". It is therefore necessary to investigate whether adjunctive therapy with inhalation Tobramycin could ameliorate prognosis. The recommendations by the Society of Infectious Diseases Pharmacists are similar.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Ventilator Associated Pneumonia (VAP)

Interventions

tobramycin inhalationDRUG

tobramycin inhalation 300 mg twice daily

placeboDRUG

NaCl 0.9% inhalation 4 ml twice daily

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Mechanical ventilation 48 hours or more * New or progressive radiologic pulmonary infiltrate Together with at least two of the following three criteria (\< 24 h): * temperature \>38°C * leukocytosis \>12,000/mm3 or leucopenia \<4,000/mm3 * purulent respiratory secretions Exclusion Criteria: * patients with allergy to tobramycin * pregnancy * expected to die within 72 hours after enrollment

Locations (2)

Erasmus MC

Rotterdam, Netherlands

Hospital Clinic

Barcelona, Spain

Outcomes

Primary Outcomes

response after 72 h of treatment

non response is considered when at least one of the following is present 1. No improvement of the arterial O2 tension to inspired O2 fraction ratio 2. Persistence of fever (≥38°C) or hypothermia (\<35.5°C) together with purulent respiratory secretions 3. increase in the pulmonary infiltrates on chest radiograph of greater than or equal to 50% 4. occurrence of septic shock or multiple organ dysfunction syndrome, defined as three or more organ system failures not present on Day 1

Time frame: 72 hours

Secondary Outcomes

Mortality rate

30-day and 90- day mortality rate

Time frame: day 30

Mortality rate

30-day and 90- day mortality rate

Time frame: day 90

ICU survival

Time frame: day 90

Absence of hospital admittance at day 60

Time frame: day 60

Discharge from the ICU

Patients will be followed during ICU stay and evaluated at discharge from ICU, expected average time of discharge is 10 days

Time frame: up to 60 days

Ventilator free days at day 28

Time frame: up to 28 days

Adverse events

Time frame: day 1

Adverse events

Time frame: day 4

Data from ClinicalTrials.gov

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