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

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ClinicalTrials.gov Identifier: NCT02440828
Recruitment Status : Unknown
Verified August 2016 by R.A.S. Hoek, MD, Erasmus Medical Center.
Recruitment status was:  Recruiting
First Posted : May 12, 2015
Last Update Posted : August 25, 2016
Sponsor:
Collaborator:
Chiesi Farmaceutici S.p.A.
Information provided by (Responsible Party):
R.A.S. Hoek, MD, 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.

Condition or disease Intervention/treatment Phase
Ventilator Associated Pneumonia (VAP) Drug: tobramycin inhalation Drug: placebo Phase 4

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Ventilator Associated Pneumonia: Addition of Tobramycin Inhalation Antibiotic Treatment to Standard IV Antibiotic Treatment
Study Start Date : March 2015
Estimated Primary Completion Date : March 2018
Estimated Study Completion Date : July 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia

Arm Intervention/treatment
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 Name: Bramitob

Placebo Comparator: Placebo
twice daily placebo inhalation and standard intravenous antibiotics treatment
Drug: placebo
NaCl 0.9% inhalation 4 ml twice daily
Other Name: NaCl 0.9% inhalation 4 ml




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Mortality rate [ Time Frame: day 30 ]
    30-day and 90- day mortality rate

  2. Mortality rate [ Time Frame: day 90 ]
    30-day and 90- day mortality rate

  3. ICU survival [ Time Frame: day 90 ]
  4. Absence of hospital admittance at day 60 [ Time Frame: day 60 ]
  5. 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

  6. Ventilator free days at day 28 [ Time Frame: up to 28 days ]
  7. Adverse events [ Time Frame: day 1 ]
  8. Adverse events [ Time Frame: day 4 ]
  9. Adverse events [ Time Frame: day 8 ]
  10. Adverse events [ Time Frame: day 14 ]
  11. Adverse events [ Time Frame: day 30 ]
  12. Adverse events [ Time Frame: day 90 ]
  13. Day of normalisation of CRP [ Time Frame: day 1 ]
  14. Day of normalisation of CRP [ Time Frame: day 4 ]
  15. Day of normalisation of CRP [ Time Frame: day 8 ]
  16. Day of normalisation of CRP [ Time Frame: day 14 ]
  17. Day of normalisation of CRP [ Time Frame: day 30 ]
  18. Day of normalisation of CRP [ Time Frame: day 90 ]
  19. Eradication of pathogens [ Time Frame: day 4 ]
  20. Eradication of pathogens [ Time Frame: day 8 ]
  21. Eradication of pathogens [ Time Frame: day 14 ]
  22. Eradication of pathogens [ Time Frame: day 30 ]
  23. Eradication of pathogens [ Time Frame: day 90 ]
  24. Clinical Pulmonary Infectious Score (CPIS) [ Time Frame: Day 1 ]
  25. Clinical Pulmonary Infectious Score (CPIS) [ Time Frame: Day 4 ]
  26. Clinical Pulmonary Infectious Score (CPIS) [ Time Frame: Day 8 ]
  27. Clinical Pulmonary Infectious Score (CPIS) [ Time Frame: Day 14 ]
  28. Clinical Pulmonary Infectious Score (CPIS) [ Time Frame: discharge ICU, expected average time of discharge is 10 days ]
  29. APACHE II score [ Time Frame: Day 1 ]
  30. APACHE II score [ Time Frame: Day 4 ]
  31. APACHE II score [ Time Frame: Day 8 ]
  32. APACHE II score [ Time Frame: Day 14 ]
  33. APACHE II score [ Time Frame: discharge ICU, expected average time of discharge is 10 days ]
  34. Multiple Organ Dysfunction score (MODS) [ Time Frame: Day 1 ]
  35. Multiple Organ Dysfunction score (MODS) [ Time Frame: Day 4 ]
  36. Multiple Organ Dysfunction score (MODS) [ Time Frame: Day 8 ]
  37. Multiple Organ Dysfunction score (MODS) [ Time Frame: Day 14 ]
  38. Multiple Organ Dysfunction score (MODS) [ Time Frame: discharge ICU, expected average time of discharge is 10 days ]
  39. Sequential Organ Failure Assessment score (SOFA) [ Time Frame: Day 1 ]
  40. Sequential Organ Failure Assessment score (SOFA) [ Time Frame: Day 4 ]
  41. Sequential Organ Failure Assessment score (SOFA) [ Time Frame: Day 8 ]
  42. Sequential Organ Failure Assessment score (SOFA) [ Time Frame: Day 14 ]
  43. Sequential Organ Failure Assessment score (SOFA) [ Time Frame: discharge ICU, expected average time of discharge is 10 days ]
  44. Lung Injury Score (LIS) [ Time Frame: Day 1 ]
  45. Lung Injury Score (LIS) [ Time Frame: Day 4 ]
  46. Lung Injury Score (LIS) [ Time Frame: Day 8 ]
  47. Lung Injury Score (LIS) [ Time Frame: Day 14 ]
  48. Lung Injury Score (LIS) [ Time Frame: discharge ICU, expected average time of discharge is 10 days ]
  49. Day of normalisation of procalcitonin (PCT) [ Time Frame: day 1 ]
  50. Day of normalisation of procalcitonin (PCT) [ Time Frame: day 4 ]
  51. Day of normalisation of procalcitonin (PCT) [ Time Frame: day 8 ]
  52. Day of normalisation of procalcitonin (PCT) [ Time Frame: day 14 ]
  53. Day of normalisation of procalcitonin (PCT) [ Time Frame: day 30 ]
  54. Day of normalisation of procalcitonin (PCT) [ Time Frame: day 90 ]
  55. Day of normalisation of chest X-ray [ Time Frame: day 1 ]
  56. Day of normalisation of chest X-ray [ Time Frame: day 4 ]
  57. Day of normalisation of chest X-ray [ Time Frame: day 8 ]
  58. Day of normalisation of chest X-ray [ Time Frame: day 14 ]
  59. Day of normalisation of chest X-ray [ Time Frame: day 30 ]
  60. Day of normalisation of chest X-ray [ Time Frame: day 90 ]


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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02440828


Contacts
Contact: Rogier Hoek, MD +31107034744 r.hoek@erasmusmc.nl
Contact: Menno Van der Eerden, MD, PhD +31107034744 m.vandereerden@erasmusmc.nl

Locations
Netherlands
Erasmus MC Recruiting
Rotterdam, Netherlands, 3000CA
Contact: Rogier Hoek, MD    +31-10-7034744    r.hoek@erasmusmc.nl   
Contact: Menno Van der eerden, MD, PhD    +31-10-7034744    m.vandereerden@erasmusmc.nl   
Spain
Hospital Clinic Not yet recruiting
Barcelona, Spain, 08036
Contact: A Torres, MD PhD Prof    93 227 5779    ATORRES@clinic.ub.es   
Sponsors and Collaborators
Erasmus Medical Center
Chiesi Farmaceutici S.p.A.
Investigators
Principal Investigator: Menno Van der Eerden, MD, PhD Erasmus MC

Responsible Party: R.A.S. Hoek, MD, MD, Erasmus Medical Center
ClinicalTrials.gov Identifier: NCT02440828     History of Changes
Other Study ID Numbers: VAP-2014
2014-001406-17 ( EudraCT Number )
First Posted: May 12, 2015    Key Record Dates
Last Update Posted: August 25, 2016
Last Verified: August 2016

Additional relevant MeSH terms:
Pneumonia, Ventilator-Associated
Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Cross Infection
Infection
Ventilator-Induced Lung Injury
Lung Injury
Anti-Bacterial Agents
Tobramycin
Antibiotics, Antitubercular
Anti-Infective Agents
Antitubercular Agents