Ventilator Associated Pneumonia (VAP)
Conditions
Brief summary
This study evaluates the addition of tobramycin inhalation treatment to standard intravenous therapy in the treatment of ventilator associated pneumonia.
Detailed description
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.
Interventions
DRUGtobramycin inhalation
tobramycin inhalation 300 mg twice daily
DRUGplacebo
NaCl 0.9% inhalation 4 ml twice daily
Sponsors
Chiesi Farmaceutici S.p.A.
Erasmus Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| response after 72 h of treatment | 72 hours | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | day 1 | — |
| Mortality rate | day 30 | 30-day and 90- day mortality rate |
| ICU survival | day 90 | — |
| Absence of hospital admittance at day 60 | day 60 | — |
| Discharge from the ICU | up to 60 days | Patients will be followed during ICU stay and evaluated at discharge from ICU, expected average time of discharge is 10 days |
| Day of normalisation of CRP | day 1 | — |
| Eradication of pathogens | day 4 | — |
| Ventilator free days at day 28 | up to 28 days | — |
| APACHE II score | Day 1 | — |
| Multiple Organ Dysfunction score (MODS) | Day 1 | — |
| Sequential Organ Failure Assessment score (SOFA) | Day 1 | — |
| Lung Injury Score (LIS) | Day 1 | — |
| Day of normalisation of procalcitonin (PCT) | day 1 | — |
| Day of normalisation of chest X-ray | day 1 | — |
| Clinical Pulmonary Infectious Score (CPIS) | Day 1 | — |
Countries
Netherlands, Spain
Outcome results
None listed