Ventilator Associated Pneumonia (VAP)Phase 4VAPORISENCT02440828
Addition of Tobramycin Inhalation in the Treatment of Ventilator Associated Pneumonia
A Phase 4 study testing tobramycin inhalation in people with Ventilator Associated Pneumonia (VAP), run by Erasmus Medical Center at 2 sites in 2 countries.
Trial summary
This study evaluates the addition of tobramycin inhalation treatment to standard intravenous therapy in the treatment of ventilator associated pneumonia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ventilator Associated Pneumonia (VAP)
- What is being tested?
- tobramycin inhalation
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Mar 2015to 1 Jul 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- patients with allergy to tobramycin
- pregnancy
- expected to die within 72 hours after enrollment
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: 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.
Read the 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.
- Conditions
- Ventilator Associated Pneumonia (VAP)
- Being tested
- tobramycin inhalation, placebo
- Medical subject headings
- Pneumonia, Ventilator-Associated
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tobramycin inhalationDrug
Also called Bramitob
tobramycin inhalation 300 mg twice daily
placeboDrug
Also called NaCl 0.9% inhalation 4 ml
NaCl 0.9% inhalation 4 ml twice daily
| Study group | Role | What they receive |
|---|---|---|
| tobramycin inhalation | Experimental | twice daily tobramycin inhalation (Bramitob) 300 mg and standard intravenous antibiotics treatment Receives: Drug: tobramycin inhalation |
| Placebo | Placebo comparator | twice daily placebo inhalation and standard intravenous antibiotics treatment Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 72 hours
Secondary outcomes (60)
Mortality rate
30-day and 90- day mortality rate
Measured: day 30
Mortality rate
30-day and 90- day mortality rate
Measured: day 90
ICU survival
Measured: day 90
Absence of hospital admittance at day 60
Measured: day 60
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
Measured: up to 60 days
Ventilator free days at day 28
Measured: up to 28 days
Adverse events
Measured: day 1
Adverse events
Measured: day 4
Adverse events
Measured: day 8
Adverse events
Measured: day 14
Adverse events
Measured: day 30
Adverse events
Measured: day 90
Day of normalisation of CRP
Measured: day 1
Day of normalisation of CRP
Measured: day 4
Day of normalisation of CRP
Measured: day 8
Day of normalisation of CRP
Measured: day 14
Day of normalisation of CRP
Measured: day 30
Day of normalisation of CRP
Measured: day 90
Eradication of pathogens
Measured: day 4
Eradication of pathogens
Measured: day 8
Eradication of pathogens
Measured: day 14
Eradication of pathogens
Measured: day 30
Eradication of pathogens
Measured: day 90
Clinical Pulmonary Infectious Score (CPIS)
Measured: Day 1
Clinical Pulmonary Infectious Score (CPIS)
Measured: Day 4
Clinical Pulmonary Infectious Score (CPIS)
Measured: Day 8
Clinical Pulmonary Infectious Score (CPIS)
Measured: Day 14
Clinical Pulmonary Infectious Score (CPIS)
Measured: discharge ICU, expected average time of discharge is 10 days
APACHE II score
Measured: Day 1
APACHE II score
Measured: Day 4
APACHE II score
Measured: Day 8
APACHE II score
Measured: Day 14
APACHE II score
Measured: discharge ICU, expected average time of discharge is 10 days
Multiple Organ Dysfunction score (MODS)
Measured: Day 1
Multiple Organ Dysfunction score (MODS)
Measured: Day 4
Multiple Organ Dysfunction score (MODS)
Measured: Day 8
Multiple Organ Dysfunction score (MODS)
Measured: Day 14
Multiple Organ Dysfunction score (MODS)
Measured: discharge ICU, expected average time of discharge is 10 days
Sequential Organ Failure Assessment score (SOFA)
Measured: Day 1
Sequential Organ Failure Assessment score (SOFA)
Measured: Day 4
Sequential Organ Failure Assessment score (SOFA)
Measured: Day 8
Sequential Organ Failure Assessment score (SOFA)
Measured: Day 14
Sequential Organ Failure Assessment score (SOFA)
Measured: discharge ICU, expected average time of discharge is 10 days
Lung Injury Score (LIS)
Measured: Day 1
Lung Injury Score (LIS)
Measured: Day 4
Lung Injury Score (LIS)
Measured: Day 8
Lung Injury Score (LIS)
Measured: Day 14
Lung Injury Score (LIS)
Measured: discharge ICU, expected average time of discharge is 10 days
Day of normalisation of procalcitonin (PCT)
Measured: day 1
Day of normalisation of procalcitonin (PCT)
Measured: day 4
Day of normalisation of procalcitonin (PCT)
Measured: day 8
Day of normalisation of procalcitonin (PCT)
Measured: day 14
Day of normalisation of procalcitonin (PCT)
Measured: day 30
Day of normalisation of procalcitonin (PCT)
Measured: day 90
Day of normalisation of chest X-ray
Measured: day 1
Day of normalisation of chest X-ray
Measured: day 4
Day of normalisation of chest X-ray
Measured: day 8
Day of normalisation of chest X-ray
Measured: day 14
Day of normalisation of chest X-ray
Measured: day 30
Day of normalisation of chest X-ray
Measured: day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2015 (estimated)
- Study startMar 2015
- Primary completion1 Mar 2020
- Study completion1 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ventilator Associated Pneumonia (VAP)Studies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Chiesi Farmaceutici S.p.A.
- Responsible party
- Principal investigator, R.A.S. Hoek, MD, Erasmus Medical Center
- Investigators
- Menno Van der Eerden, MD, PhD, Principal investigator, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02440828
- Sponsor's protocol ID
- VAP-2014
- Other IDs
- 2014-001406-17, 2014
- Acronym
- VAPORISE
- Status last verified
- Aug 2021
- First submitted
- 13 Mar 2015
- Last updated
- 18 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ventilator Associated Pneumonia: Addition of Tobramycin Inhalation Antibiotic Treatment to Standard IV Antibiotic Treatment
- ClinicalTrials.gov ID
- NCT02440828
- Acronym / sponsor ID
- VAPORISE / VAP-2014
- Conditions
- Ventilator Associated Pneumonia (VAP)
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Collaborators
- Chiesi Farmaceutici S.p.A.
- Study start
- Mar 2015
- Primary completion
- 1 Mar 2020 (actual)
- Study completion
- 1 Jul 2020 (actual)
- First posted
- 12 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| tobramycin inhalation | Experimental | Drug: tobramycin inhalationtwice daily tobramycin inhalation (Bramitob) 300 mg and standard intravenous antibiotics treatment |
| Placebo | Placebo comparator | Drug: placebotwice daily placebo inhalation and standard intravenous antibiotics treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Mechanical ventilation 48 hours or more
- New or progressive radiologic pulmonary infiltrate
- temperature >38°C
- leukocytosis >12,000/mm3 or leucopenia <4,000/mm3
- purulent respiratory secretions
Key exclusion criteria (3 listed)
- patients with allergy to tobramycin
- pregnancy
- expected to die within 72 hours after enrollment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| tobramycin inhalationAlso: Bramitobtobramycin inhalation 300 mg twice daily | Drug | tobramycin inhalation |
| placeboAlso: NaCl 0.9% inhalation 4 mlNaCl 0.9% inhalation 4 ml twice daily | Drug | Placebo |
Primary outcome
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
60 secondary outcomes
Mortality rate
Time frame: day 30
Mortality rate
Time frame: day 90
ICU survival
Time frame: day 90
Absence of hospital admittance at day 60
Time frame: day 60
Discharge from the ICU
Time frame: up to 60 days
Ventilator free days at day 28
Time frame: up to 28 days
Adverse events
Time frame: day 1
Adverse events
Time frame: day 4
Adverse events
Time frame: day 8
Adverse events
Time frame: day 14
Adverse events
Time frame: day 30
Adverse events
Time frame: day 90
Day of normalisation of CRP
Time frame: day 1
Day of normalisation of CRP
Time frame: day 4
Day of normalisation of CRP
Time frame: day 8
Day of normalisation of CRP
Time frame: day 14
Day of normalisation of CRP
Time frame: day 30
Day of normalisation of CRP
Time frame: day 90
Eradication of pathogens
Time frame: day 4
Eradication of pathogens
Time frame: day 8
Eradication of pathogens
Time frame: day 14
Eradication of pathogens
Time frame: day 30
Eradication of pathogens
Time frame: day 90
Clinical Pulmonary Infectious Score (CPIS)
Time frame: Day 1
Clinical Pulmonary Infectious Score (CPIS)
Time frame: Day 4
Clinical Pulmonary Infectious Score (CPIS)
Time frame: Day 8
Clinical Pulmonary Infectious Score (CPIS)
Time frame: Day 14
Clinical Pulmonary Infectious Score (CPIS)
Time frame: discharge ICU, expected average time of discharge is 10 days
APACHE II score
Time frame: Day 1
APACHE II score
Time frame: Day 4
APACHE II score
Time frame: Day 8
APACHE II score
Time frame: Day 14
APACHE II score
Time frame: discharge ICU, expected average time of discharge is 10 days
Multiple Organ Dysfunction score (MODS)
Time frame: Day 1
Multiple Organ Dysfunction score (MODS)
Time frame: Day 4
Multiple Organ Dysfunction score (MODS)
Time frame: Day 8
Multiple Organ Dysfunction score (MODS)
Time frame: Day 14
Multiple Organ Dysfunction score (MODS)
Time frame: discharge ICU, expected average time of discharge is 10 days
Sequential Organ Failure Assessment score (SOFA)
Time frame: Day 1
Sequential Organ Failure Assessment score (SOFA)
Time frame: Day 4
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Menno Van der Eerden, MD, PhD principal investigator
Erasmus Medical Center
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing tobramycin inhalation in people with Ventilator Associated Pneumonia (VAP), run by Erasmus Medical Center at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
response after 72 h of treatment (time frame: 72 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2021.