Burn Injury, Inhalation Injury
Conditions
Keywords
Inhalation trauma, pulmonary coagulopathy, heparin nebulization, mechanical ventilation
Brief summary
The purpose of this international multi-center double-blind randomized placebo-controlled trial is to determine the effect of nebulized heparin, compared to placebo, on the number of ventilator-free days at day 28, in burn patients with confirmed inhalation trauma requiring mechanical ventilation.
Interventions
DRUGunfractionated heparin
nebulized 6 times daily, daily dose 150.000 IU for the maximum duration of 14 days
DRUGplacebo
Placebo: Sterile saline nebulized 6 times daily for the maximum duration of 14 days
Sponsors
Dutch Burns Foundation
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Informed consent * Age \> 18 years * Need for invasive mechanical ventilation * Confirmed inhalation trauma (bronchoscopically)
Exclusion criteria
* \> 36 hours after trauma * Receiving invasive ventilation \> 24 hours * Expected duration of mechanical ventilation \< 24 hours * Chronic obstructive pulmonary disease GOLD stage III and IV * Any history of pulmonary hemorrhage in the past 3 months * Any history of significant bleeding disorder * Known allergy to heparin, including heparin-induced thrombocytopenia * Pregnancy or breast feeding * Unlikely to survive for \> 72 hours * Total body surface area (TBSA) \> 60% * Witnessed or proven aspiration (i.e., confirmed by bronchoscopy)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of ventilator-free days at day 28 | at day 28 | The number of ventilator-free days is defined as the number of days a patient is breathing without assist of a ventilator during the first 28 days; thus, the patient must be free of mechanical ventilation for 24 hours to have one ventilator-free day; if after successful detubation the patient requires a reintubation due to a surgical procedure, this reintubation will not count as a ventilator day - however, the day(s) will be counted as ventilator day(s) if mechanical ventilation is prolonged after surgery due to respiratory insufficiency. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical outcome parameters | daily or at day 28 and day 90 | Clinical outcome parameters will include but not be restricted to: (a) length of stay (ICU and hospital); (b) mortality (28- and 90 days); (c) mortality (ICU and hospital); (d) daily Lung Injury Score (LIS); (e) daily Oxygenation Index (OI) ; (f) daily Sequential Organ Failure Assessment (SOFA)-scores ; (g) cumulative dosages of sedatives; (h) incidence of Ventilator-associated Pneumonia (VAP); (i) total number of bronchoscopy-guided cleaning of the larger airway |
| Laboratory outcome parameters | Blood and lavage samples: on admission day and every other day for a maximum period of 14 days | Levels of markers of coagulation and fibrinolysis in blood and lung lavage fluid, Levels of markers of inflammation in blood and lung lavage fluid, Biomarkers of lung injury in blood and lung lavage fluid |
| Safety parameters | daily, for a maximum period of 28 days | Safety parameters will include but not be restricted to: Occurrence of serious bleedings, any other transfusion of blood products - red cells and/or platelets and/or plasma, Confirmed Heparin induced thrombocytopenia, prolonged activated partial thromboplastin time (aPTT \> 150 seconds) |
Countries
Australia, Belgium, Netherlands
Outcome results
None listed