Tracheobronchitis Prevention Trial (TRAMA)

• ClinicalTrials.gov Identifier: NCT01025921
• Recruitment Status: Completed
• First Posted: December 4, 2009
• Last Update Posted: June 3, 2013
• Sponsor: University of Thessaly
• Information provided by (Responsible Party): Efstratios Manoulakas, University of Thessaly

Study Description

Brief Summary:

We aim to study whether the use of inhaled antibiotics may have an impact on the incidence of tracheobronchitis and pneumonia associated with the use of mechanical ventilation. The investigators hypothesize that this could be possible by decreasing the population of gram negative germs that colonize the lumen of tracheal tube and upper airways.

Condition or disease	Intervention/treatment	Phase
Tracheobronchitis; Pneumonia	Drug: colistin (Tadim); Other: inhaled normal saline	Not Applicable

Detailed Description:

INTRODUCTION Gram-negative bacteria have recently become endemic in many ICUs around the world. Ventilator associated pneumonia (VAP) is relatively common and its parenteral treatment often leads to low and sub-therapeutic concentrations of antibiotics in the lung. Ventilator associated tracheobronchitis (VAT) is characterized by fever, purulent sputum, positive cultures of tracheal aspirates secretions and the absence of new pulmonary infiltrates on CXR. This entity is of particular interest because it is an intermediate step in the pathogenesis of VAP (between colonization and VAP itself) and prolongs mechanical ventilatory support. Inhaled antibiotics achieve high (both peak and trough) concentrations in respiratory secretions. Endobronchial antibiotics have been given to non-cystic fibrosis patients for prevention of VAP. Colistimethate sodium (colistin) given by instillation decreased the incidence of Gram-negative pneumonia and did not lead to the development of colistin resistant bacteria.

AIM

The study is a prospective open label randomized study which aims to clarify the effect of colistin to:

1. The incidence of VAP The incidence of VAT
2. Mechanical ventilation free days
3. Incidence of multidrug resistant bacteria in tracheal aspirates cultures

METHODS Settings: The study will be performed in the ICU of the University of Larissa (12 beds).

Entry criteria: All intubated and tracheostomised patients, older than 18 years old with duration of intubation of 48 hours.

Exclusion criteria: 1) Purulent sputum within 48 hours from admission. 2) Pneumonia within 48 hours of intubation 3) New chest X ray infiltrate, 4) Advanced COPD that led to intubation 5) Pregnancy 6) Allergy to colistin 7) Resistance of the bacterial strain to colistin.

Tools: Randomization of the patients into two groups: the first group will receive nebulized colistin and the other no treatment. The initial dose is 1000000 units and it will be doubled after measurement of the drug concentration in tracheal secretions. The drug will start on admission and stop after 10 days.

All patients will be given the respiratory bundle measures (semi-recumbent position, daily interruption of sedation) as part of the usual daily practice of our ICU except otherwise indicated.

The severity of patients will be estimated by APACHE II score on admission and SOFA score thrice weekly. CPIS score as a screening tool for pneumonia will be estimated as well thrice weekly.

Tracheal aspirates cultures on admission and thrice weekly thereafter for the first two weeks and twice weekly thereafter.

The patients will be followed for thirty days to measure outcome.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 84 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Study of Inhaled Antibiotics for Prevention of Tracheobronchitis and Ventilator Associated Pneumonia
• Study Start Date: November 2009
• Actual Primary Completion Date: May 2013
• Actual Study Completion Date: May 2013

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Inhaled colistin; They will receive inhaled colistin three times daily for 10 days.	Drug: colistin (Tadim); 500.000 units of inhaled colistin three times daily for 10 days
Placebo Comparator: Inhaled normal saline; Inhaled normal saline three times daily for 10 days	Other: inhaled normal saline; inhalation of 2,5cc Normal Saline via nebulisation

Outcome Measures

Primary Outcome Measures :

1. Incidence of tracheobronchitis and ventilator associated pneumonia [ Time Frame: 30 days ]

Secondary Outcome Measures :

1. Ventilator free days and ICU length of stay [ Time Frame: 30 days ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• All intubated and tracheostomized patients, older than 18 years old with duration of intubation of 48 hours.

Exclusion Criteria:

• Purulent sputum within 48 hours from admission
• Pneumonia within 48 hours of intubation
• New chest X ray infiltrate
• Advanced COPD that led to intubation
• Pregnancy
• Allergy to colistin
• Resistance of the bacterial strain to colistin

Contacts and Locations

Locations

Greece

University Hospital of Larissa

Larissa, Greece, 41110

Sponsors and Collaborators

University of Thessaly

More Information

• Responsible Party: Efstratios Manoulakas, Professor and ICU Director Zakynthinos Epaminondas, University of Thessaly
• ClinicalTrials.gov Identifier: NCT01025921
• Other Study ID Numbers: MARKAR161109
• First Posted: December 4, 2009
• Last Update Posted: June 3, 2013
• Last Verified: May 2013

Keywords provided by Efstratios Manoulakas, University of Thessaly:

Tracheobronchitis; pneumonia; inhaled antibiotics; colistin; Ventilator associated tracheobronchitis; Ventilator associated pneumonia

Additional relevant MeSH terms:

Pneumonia; Lung Diseases; Respiratory Tract Diseases; Respiratory Tract Infections; Colistin; Anti-Bacterial Agents; Anti-Infective Agents