Clinical trial NCT02440828: Addition of Tobramycin Inhalation in the Treatment of Ventilator Associated Pneumonia
Official title: Ventilator Associated Pneumonia: Addition of Tobramycin Inhalation Antibiotic Treatment to Standard IV Antibiotic Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Ventilator Associated Pneumonia (VAP)
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
Collaborators: name: Chiesi Farmaceutici S.p.A.
First posted: 2015-05-12
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: response after 72 h of treatment
timeFrame: 72 hours
Secondary outcomes:
measure: Mortality rate
timeFrame: day 30
measure: Mortality rate
timeFrame: day 90
measure: ICU survival
timeFrame: day 90
measure: Absence of hospital admittance at day 60
timeFrame: day 60
measure: Discharge from the ICU
timeFrame: up to 60 days
measure: Ventilator free days at day 28
timeFrame: up to 28 days
measure: Adverse events
timeFrame: day 1
measure: Adverse events
timeFrame: day 4
measure: Adverse events
timeFrame: day 8
measure: Adverse events
timeFrame: day 14
measure: Adverse events
timeFrame: day 30
measure: Adverse events
timeFrame: day 90
measure: Day of normalisation of CRP
timeFrame: day 1
measure: Day of normalisation of CRP
timeFrame: day 4
measure: Day of normalisation of CRP
timeFrame: day 8
measure: Day of normalisation of CRP
timeFrame: day 14
measure: Day of normalisation of CRP
timeFrame: day 30
measure: Day of normalisation of CRP
timeFrame: day 90
measure: Eradication of pathogens
timeFrame: day 4
measure: Eradication of pathogens
timeFrame: day 8
measure: Eradication of pathogens
timeFrame: day 14
measure: Eradication of pathogens
timeFrame: day 30
measure: Eradication of pathogens
timeFrame: day 90
measure: Clinical Pulmonary Infectious Score (CPIS)
timeFrame: Day 1
measure: Clinical Pulmonary Infectious Score (CPIS)
timeFrame: Day 4
measure: Clinical Pulmonary Infectious Score (CPIS)
timeFrame: Day 8
measure: Clinical Pulmonary Infectious Score (CPIS)
timeFrame: Day 14
measure: Clinical Pulmonary Infectious Score (CPIS)
timeFrame: discharge ICU, expected average time of discharge is 10 days
measure: APACHE II score
timeFrame: Day 1
measure: APACHE II score
timeFrame: Day 4
measure: APACHE II score
timeFrame: Day 8
measure: APACHE II score
timeFrame: Day 14
measure: APACHE II score
timeFrame: discharge ICU, expected average time of discharge is 10 days
measure: Multiple Organ Dysfunction score (MODS)
timeFrame: Day 1
measure: Multiple Organ Dysfunction score (MODS)
timeFrame: Day 4
measure: Multiple Organ Dysfunction score (MODS)
timeFrame: Day 8
measure: Multiple Organ Dysfunction score (MODS)
timeFrame: Day 14
measure: Multiple Organ Dysfunction score (MODS)
timeFrame: discharge ICU, expected average time of discharge is 10 days
measure: Sequential Organ Failure Assessment score (SOFA)
timeFrame: Day 1
measure: Sequential Organ Failure Assessment score (SOFA)
timeFrame: Day 4
measure: Sequential Organ Failure Assessment score (SOFA)
timeFrame: Day 8
measure: Sequential Organ Failure Assessment score (SOFA)
timeFrame: Day 14
measure: Sequential Organ Failure Assessment score (SOFA)
timeFrame: discharge ICU, expected average time of discharge is 10 days
measure: Lung Injury Score (LIS)
timeFrame: Day 1
measure: Lung Injury Score (LIS)
timeFrame: Day 4
measure: Lung Injury Score (LIS)
timeFrame: Day 8
measure: Lung Injury Score (LIS)
timeFrame: Day 14
measure: Lung Injury Score (LIS)
timeFrame: discharge ICU, expected average time of discharge is 10 days
measure: Day of normalisation of procalcitonin (PCT)
timeFrame: day 1
measure: Day of normalisation of procalcitonin (PCT)
timeFrame: day 4
measure: Day of normalisation of procalcitonin (PCT)
timeFrame: day 8
measure: Day of normalisation of procalcitonin (PCT)
timeFrame: day 14
measure: Day of normalisation of procalcitonin (PCT)
timeFrame: day 30
measure: Day of normalisation of procalcitonin (PCT)
timeFrame: day 90
measure: Day of normalisation of chest X-ray
timeFrame: day 1
measure: Day of normalisation of chest X-ray
timeFrame: day 4
measure: Day of normalisation of chest X-ray
timeFrame: day 8
measure: Day of normalisation of chest X-ray
timeFrame: day 14
measure: Day of normalisation of chest X-ray
timeFrame: day 30
measure: Day of normalisation of chest X-ray
timeFrame: day 90
Other outcomes:
Locations:
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Barcelona
country: Spain
facility: Hospital Clinic
Study officials:
affiliation: Erasmus Medical Center
name: Menno Van der Eerden, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: