Addition of Tobramycin Inhalation in the Treatment of Ventilator Associated Pneumonia

Phase 4

Completed

• Conditions: Ventilator Associated Pneumonia (VAP)
• Interventions: Drug: placebo; Drug: tobramycin inhalation

• Registration Number: NCT02440828
• Lead Sponsor: Erasmus Medical Center

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.

Study Timeline

• Study Start: 2015-03
• Study First Submitted: 2015-03-13
• Study First Submitted QC: 2015-05-11
• Study First Posted: 2015-05-12
• Primary Completion: 2020-03-01
• Study Completion: 2020-07-01
• Status Verified: 2021-08
• Last Update Submitted: 2021-08-17
• Last Update Posted: 2021-08-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 80

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	placebo	twice daily placebo inhalation and standard intravenous antibiotics treatment
tobramycin inhalation	tobramycin inhalation	twice daily tobramycin inhalation (Bramitob) 300 mg and standard intravenous antibiotics treatment

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Mortality rate	day 90	30-day and 90- day mortality rate
Ventilator free days at day 28	up to 28 days
Day of normalisation of CRP	day 90
APACHE II score	discharge ICU, expected average time of discharge is 10 days
Sequential Organ Failure Assessment score (SOFA)	discharge ICU, expected average time of discharge is 10 days
Lung Injury Score (LIS)	discharge ICU, expected average time of discharge is 10 days
Day of normalisation of chest X-ray	day 90
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
Absence of hospital admittance at day 60	day 60
Eradication of pathogens	day 90
Clinical Pulmonary Infectious Score (CPIS)	discharge ICU, expected average time of discharge is 10 days
Multiple Organ Dysfunction score (MODS)	discharge ICU, expected average time of discharge is 10 days
Day of normalisation of procalcitonin (PCT)	day 90
ICU survival	day 90
Adverse events	day 90

Trial Locations

Locations (2)

Erasmus MC; 🇳🇱 Rotterdam, Netherlands

Hospital Clinic; 🇪🇸 Barcelona, Spain