Trial of Nebulized Heparin Versus Placebo for Inhalation Trauma

Study Overview
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Brief Summary
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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.

Official Title
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Randomized Controlled Trial Investigating the Efficacy and Safety of Nebulized Heparin Versus Placebo in Burn Patients With Inhalation Trauma (Hepburn)

Conditions
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Inhalation Injury, Burn Injury

Intervention / Treatment
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* Drug: unfractionated heparin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: unfractionated heparin<br>25.000 IU/5 ml, will be nebulized 4 hourly (i.e. 6 times daily) | Drug: unfractionated heparin<br>* nebulized 6 times daily, daily dose 150.000 IU for the maximum duration of 14 days<br>* Other names: ATC codes: B01AB01;|
| Placebo Comparator: placebo<br>Sterile sodium chloride (NaCl 0.9%, Pfizer), in 5 ml, will be nebulized every 4 hours (i.e. 6 times daily) | Drug: placebo<br>* Placebo: Sterile saline nebulized 6 times daily for the maximum duration of 14 days<br>* Other names: sterile sodium chloride (NaCl 0.9%);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of ventilator-free days 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. | at day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical outcome parameters | 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 | daily or at day 28 and day 90 | 
| Laboratory outcome parameters | 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 | Blood and lavage samples: on admission day and every other day for a maximum period of 14 days | 
| Safety parameters | 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) | daily, for a maximum period of 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Inhalation trauma, pulmonary coagulopathy, heparin nebulization, mechanical ventilation