Addition of Tobramycin Inhalation in the Treatment of Ventilator Associated Pneumonia (VAPORISE)

August 17, 2021 updated by: R.A.S. Hoek, MD, Erasmus Medical Center

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

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Rotterdam, Netherlands, 3000CA
        • Erasmus MC
  • Spain
      • Barcelona, Spain, 08036
        • Hospital Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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:
  • Bramitob
Placebo Comparator: Placebo
twice daily placebo inhalation and standard intravenous antibiotics treatment
Drug: placebo
NaCl 0.9% inhalation 4 ml twice daily
Other Names:
  • NaCl 0.9% inhalation 4 ml

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
response after 72 h of treatment
Time Frame: 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
72 hours

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Mortality rate
Time Frame: day 30
30-day and 90- day mortality rate
day 30
Mortality rate
Time Frame: day 90
30-day and 90- day mortality rate
day 90
ICU survival
Time Frame: day 90
day 90
Absence of hospital admittance at day 60
Time Frame: day 60
day 60
Discharge from the ICU
Time Frame: 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
up to 60 days
Ventilator free days at day 28
Time Frame: up to 28 days
up to 28 days
Adverse events
Time Frame: day 1
day 1
Adverse events
Time Frame: day 4
day 4
Adverse events
Time Frame: day 8
day 8
Adverse events
Time Frame: day 14
day 14
Adverse events
Time Frame: day 30
day 30
Adverse events
Time Frame: day 90
day 90
Day of normalisation of CRP
Time Frame: day 1
day 1
Day of normalisation of CRP
Time Frame: day 4
day 4
Day of normalisation of CRP
Time Frame: day 8
day 8
Day of normalisation of CRP
Time Frame: day 14
day 14
Day of normalisation of CRP
Time Frame: day 30
day 30
Day of normalisation of CRP
Time Frame: day 90
day 90
Eradication of pathogens
Time Frame: day 4
day 4
Eradication of pathogens
Time Frame: day 8
day 8
Eradication of pathogens
Time Frame: day 14
day 14
Eradication of pathogens
Time Frame: day 30
day 30
Eradication of pathogens
Time Frame: day 90
day 90
Clinical Pulmonary Infectious Score (CPIS)
Time Frame: Day 1
Day 1
Clinical Pulmonary Infectious Score (CPIS)
Time Frame: Day 4
Day 4
Clinical Pulmonary Infectious Score (CPIS)
Time Frame: Day 8
Day 8
Clinical Pulmonary Infectious Score (CPIS)
Time Frame: Day 14
Day 14
Clinical Pulmonary Infectious Score (CPIS)
Time Frame: discharge ICU, expected average time of discharge is 10 days
discharge ICU, expected average time of discharge is 10 days
APACHE II score
Time Frame: Day 1
Day 1
APACHE II score
Time Frame: Day 4
Day 4
APACHE II score
Time Frame: Day 8
Day 8
APACHE II score
Time Frame: Day 14
Day 14
APACHE II score
Time Frame: discharge ICU, expected average time of discharge is 10 days
discharge ICU, expected average time of discharge is 10 days
Multiple Organ Dysfunction score (MODS)
Time Frame: Day 1
Day 1
Multiple Organ Dysfunction score (MODS)
Time Frame: Day 4
Day 4
Multiple Organ Dysfunction score (MODS)
Time Frame: Day 8
Day 8
Multiple Organ Dysfunction score (MODS)
Time Frame: Day 14
Day 14
Multiple Organ Dysfunction score (MODS)
Time Frame: discharge ICU, expected average time of discharge is 10 days
discharge ICU, expected average time of discharge is 10 days
Sequential Organ Failure Assessment score (SOFA)
Time Frame: Day 1
Day 1
Sequential Organ Failure Assessment score (SOFA)
Time Frame: Day 4
Day 4
Sequential Organ Failure Assessment score (SOFA)
Time Frame: Day 8
Day 8
Sequential Organ Failure Assessment score (SOFA)
Time Frame: Day 14
Day 14
Sequential Organ Failure Assessment score (SOFA)
Time Frame: discharge ICU, expected average time of discharge is 10 days
discharge ICU, expected average time of discharge is 10 days
Lung Injury Score (LIS)
Time Frame: Day 1
Day 1
Lung Injury Score (LIS)
Time Frame: Day 4
Day 4
Lung Injury Score (LIS)
Time Frame: Day 8
Day 8
Lung Injury Score (LIS)
Time Frame: Day 14
Day 14
Lung Injury Score (LIS)
Time Frame: discharge ICU, expected average time of discharge is 10 days
discharge ICU, expected average time of discharge is 10 days
Day of normalisation of procalcitonin (PCT)
Time Frame: day 1
day 1
Day of normalisation of procalcitonin (PCT)
Time Frame: day 4
day 4
Day of normalisation of procalcitonin (PCT)
Time Frame: day 8
day 8
Day of normalisation of procalcitonin (PCT)
Time Frame: day 14
day 14
Day of normalisation of procalcitonin (PCT)
Time Frame: day 30
day 30
Day of normalisation of procalcitonin (PCT)
Time Frame: day 90
day 90
Day of normalisation of chest X-ray
Time Frame: day 1
day 1
Day of normalisation of chest X-ray
Time Frame: day 4
day 4
Day of normalisation of chest X-ray
Time Frame: day 8
day 8
Day of normalisation of chest X-ray
Time Frame: day 14
day 14
Day of normalisation of chest X-ray
Time Frame: day 30
day 30
Day of normalisation of chest X-ray
Time Frame: day 90
day 90

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Erasmus Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Chiesi Farmaceutici S.p.A.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Menno Van der Eerden, MD, PhD, Erasmus Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 13, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 11, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 12, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 18, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 17, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • VAP-2014
  • 2014-001406-17 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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