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Completed

NCT Number: NCT02440828

Addition of Tobramycin Inhalation in the Treatment of Ventilator Associated Pneumonia

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

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Erasmus MC, Rotterdam, Netherlands

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

tobramycin inhalation

Drug

tobramycin inhalation 300 mg twice daily

Other names: Bramitob

Placebo

Drug

NaCl 0.9% inhalation 4 ml twice daily

Other names: NaCl 0.9% inhalation 4 ml

Primary outcomes

  1. response after 72 h of treatment

    Time frame: 72 hours

    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

Secondary outcomes

  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

Sponsors and collaborators

Lead sponsor

Erasmus Medical Center

Other

Collaborators

  • Chiesi Farmaceutici S.p.A.

Registry information

Official study title

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

Acronym: VAPORISE

Important dates

Study start
2015
Primary completion
2020
Study completion
2020
First posted
May 12, 2015
Registry last updated
Aug 18, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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