Addition of Tobramycin Inhalation in the Treatment of Ventilator Associated Pneumonia

Ventilator Associated Pneumonia (VAP) Clinical Trial

— VAPORISE  

Official title:

Ventilator Associated Pneumonia: Addition of Tobramycin Inhalation Antibiotic Treatment to Standard IV Antibiotic Treatment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02440828
• Other study ID #: VAP-2014
• Secondary ID: 2014-001406-17
• Status: Completed
• Phase: Phase 4
• Start date: March 2015
• Est. completion date: July 1, 2020

Study information

• Verified date: August 2021
• Source: Erasmus Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: July 1, 2020
• Est. primary completion date: March 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pneumonia
• Pneumonia, Ventilator-Associated
• Ventilator Associated Pneumonia (VAP)

Intervention

Drug:
• tobramycin inhalation
tobramycin inhalation 300 mg twice daily
• placebo
NaCl 0.9% inhalation 4 ml twice daily

Locations

Country	Name	City	State
Netherlands	Erasmus MC	Rotterdam
Spain	Hospital Clinic	Barcelona

Sponsors (2)

Lead Sponsor	Collaborator
Erasmus Medical Center	Chiesi Farmaceutici S.p.A.

Countries where clinical trial is conducted

Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	response after 72 h of treatment	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	72 hours
Secondary	Mortality rate	30-day and 90- day mortality rate	day 30
Secondary	Mortality rate	30-day and 90- day mortality rate	day 90
Secondary	ICU survival		day 90
Secondary	Absence of hospital admittance at day 60		day 60
Secondary	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	up to 60 days
Secondary	Ventilator free days at day 28		up to 28 days
Secondary	Adverse events		day 1
Secondary	Adverse events		day 4
Secondary	Adverse events		day 8
Secondary	Adverse events		day 14
Secondary	Adverse events		day 30
Secondary	Adverse events		day 90
Secondary	Day of normalisation of CRP		day 1
Secondary	Day of normalisation of CRP		day 4
Secondary	Day of normalisation of CRP		day 8
Secondary	Day of normalisation of CRP		day 14
Secondary	Day of normalisation of CRP		day 30
Secondary	Day of normalisation of CRP		day 90
Secondary	Eradication of pathogens		day 4
Secondary	Eradication of pathogens		day 8
Secondary	Eradication of pathogens		day 14
Secondary	Eradication of pathogens		day 30
Secondary	Eradication of pathogens		day 90
Secondary	Clinical Pulmonary Infectious Score (CPIS)		Day 1
Secondary	Clinical Pulmonary Infectious Score (CPIS)		Day 4
Secondary	Clinical Pulmonary Infectious Score (CPIS)		Day 8
Secondary	Clinical Pulmonary Infectious Score (CPIS)		Day 14
Secondary	Clinical Pulmonary Infectious Score (CPIS)		discharge ICU, expected average time of discharge is 10 days
Secondary	APACHE II score		Day 1
Secondary	APACHE II score		Day 4
Secondary	APACHE II score		Day 8
Secondary	APACHE II score		Day 14
Secondary	APACHE II score		discharge ICU, expected average time of discharge is 10 days
Secondary	Multiple Organ Dysfunction score (MODS)		Day 1
Secondary	Multiple Organ Dysfunction score (MODS)		Day 4
Secondary	Multiple Organ Dysfunction score (MODS)		Day 8
Secondary	Multiple Organ Dysfunction score (MODS)		Day 14
Secondary	Multiple Organ Dysfunction score (MODS)		discharge ICU, expected average time of discharge is 10 days
Secondary	Sequential Organ Failure Assessment score (SOFA)		Day 1
Secondary	Sequential Organ Failure Assessment score (SOFA)		Day 4
Secondary	Sequential Organ Failure Assessment score (SOFA)		Day 8
Secondary	Sequential Organ Failure Assessment score (SOFA)		Day 14
Secondary	Sequential Organ Failure Assessment score (SOFA)		discharge ICU, expected average time of discharge is 10 days
Secondary	Lung Injury Score (LIS)		Day 1
Secondary	Lung Injury Score (LIS)		Day 4
Secondary	Lung Injury Score (LIS)		Day 8
Secondary	Lung Injury Score (LIS)		Day 14
Secondary	Lung Injury Score (LIS)		discharge ICU, expected average time of discharge is 10 days
Secondary	Day of normalisation of procalcitonin (PCT)		day 1
Secondary	Day of normalisation of procalcitonin (PCT)		day 4
Secondary	Day of normalisation of procalcitonin (PCT)		day 8
Secondary	Day of normalisation of procalcitonin (PCT)		day 14
Secondary	Day of normalisation of procalcitonin (PCT)		day 30
Secondary	Day of normalisation of procalcitonin (PCT)		day 90
Secondary	Day of normalisation of chest X-ray		day 1
Secondary	Day of normalisation of chest X-ray		day 4
Secondary	Day of normalisation of chest X-ray		day 8
Secondary	Day of normalisation of chest X-ray		day 14
Secondary	Day of normalisation of chest X-ray		day 30
Secondary	Day of normalisation of chest X-ray		day 90