VAPORISE: Addition of Tobramycin Inhalation in the Treatment of Ventilator Associated Pneumonia
Study Details
Study Description
Brief Summary
This study evaluates the addition of tobramycin inhalation treatment to standard intravenous therapy in the treatment of ventilator associated pneumonia.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: tobramycin inhalation twice daily tobramycin inhalation (Bramitob) 300 mg and standard intravenous antibiotics treatment |
Drug: tobramycin inhalation
tobramycin inhalation 300 mg twice daily
Other Names:
|
| Placebo Comparator: Placebo twice daily placebo inhalation and standard intravenous antibiotics treatment |
Drug: placebo
NaCl 0.9% inhalation 4 ml twice daily
Other Names:
|
Outcome Measures
Primary Outcome Measures
- response after 72 h of treatment [72 hours]
non response is considered when at least one of the following is present No improvement of the arterial O2 tension to inspired O2 fraction ratio Persistence of fever (≥38°C) or hypothermia (<35.5°C) together with purulent respiratory secretions increase in the pulmonary infiltrates on chest radiograph of greater than or equal to 50% occurrence of septic shock or multiple organ dysfunction syndrome, defined as three or more organ system failures not present on Day 1
Secondary Outcome Measures
- Mortality rate [day 30]
30-day and 90- day mortality rate
- Mortality rate [day 90]
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
- Ventilator free days at day 28 [up to 28 days]
- Adverse events [day 1]
- Adverse events [day 4]
- Adverse events [day 8]
- Adverse events [day 14]
- Adverse events [day 30]
- Adverse events [day 90]
- Day of normalisation of CRP [day 1]
- Day of normalisation of CRP [day 4]
- Day of normalisation of CRP [day 8]
- Day of normalisation of CRP [day 14]
- Day of normalisation of CRP [day 30]
- Day of normalisation of CRP [day 90]
- Eradication of pathogens [day 4]
- Eradication of pathogens [day 8]
- Eradication of pathogens [day 14]
- Eradication of pathogens [day 30]
- Eradication of pathogens [day 90]
- Clinical Pulmonary Infectious Score (CPIS) [Day 1]
- Clinical Pulmonary Infectious Score (CPIS) [Day 4]
- Clinical Pulmonary Infectious Score (CPIS) [Day 8]
- Clinical Pulmonary Infectious Score (CPIS) [Day 14]
- Clinical Pulmonary Infectious Score (CPIS) [discharge ICU, expected average time of discharge is 10 days]
- APACHE II score [Day 1]
- APACHE II score [Day 4]
- APACHE II score [Day 8]
- APACHE II score [Day 14]
- APACHE II score [discharge ICU, expected average time of discharge is 10 days]
- Multiple Organ Dysfunction score (MODS) [Day 1]
- Multiple Organ Dysfunction score (MODS) [Day 4]
- Multiple Organ Dysfunction score (MODS) [Day 8]
- Multiple Organ Dysfunction score (MODS) [Day 14]
- Multiple Organ Dysfunction score (MODS) [discharge ICU, expected average time of discharge is 10 days]
- Sequential Organ Failure Assessment score (SOFA) [Day 1]
- Sequential Organ Failure Assessment score (SOFA) [Day 4]
- Sequential Organ Failure Assessment score (SOFA) [Day 8]
- Sequential Organ Failure Assessment score (SOFA) [Day 14]
- Sequential Organ Failure Assessment score (SOFA) [discharge ICU, expected average time of discharge is 10 days]
- Lung Injury Score (LIS) [Day 1]
- Lung Injury Score (LIS) [Day 4]
- Lung Injury Score (LIS) [Day 8]
- Lung Injury Score (LIS) [Day 14]
- Lung Injury Score (LIS) [discharge ICU, expected average time of discharge is 10 days]
- Day of normalisation of procalcitonin (PCT) [day 1]
- Day of normalisation of procalcitonin (PCT) [day 4]
- Day of normalisation of procalcitonin (PCT) [day 8]
- Day of normalisation of procalcitonin (PCT) [day 14]
- Day of normalisation of procalcitonin (PCT) [day 30]
- Day of normalisation of procalcitonin (PCT) [day 90]
- Day of normalisation of chest X-ray [day 1]
- Day of normalisation of chest X-ray [day 4]
- Day of normalisation of chest X-ray [day 8]
- Day of normalisation of chest X-ray [day 14]
- Day of normalisation of chest X-ray [day 30]
- Day of normalisation of chest X-ray [day 90]
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Erasmus MC | Rotterdam | Netherlands | 3000CA | |
| 2 | Hospital Clinic | Barcelona | Spain | 08036 |
Sponsors and Collaborators
- Erasmus Medical Center
- Chiesi Farmaceutici S.p.A.
Investigators
- Principal Investigator: Menno Van der Eerden, MD, PhD, Erasmus MC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- VAP-2014
- 2014-001406-17