TRAUMADORNASE: Inhaled Dornase Alpha to Reduce Respiratory Failure After Severe Trauma

Sponsor

University Hospital, Strasbourg, France (Other)

Overall Status

Recruiting

CT.gov ID

NCT03368092

Collaborator

(none)

500

Enrollment

Location

Arms

Anticipated Duration (Months)

7.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Severe hypoxemia following trauma may happen in many circumstances (aspiration, ventilation-associated pneumonia, lung contusion...), most of which are not exclusively associated with a direct injury to the lungs. Severe trauma and associated musculoskeletal injuries result in the acute release of Damage-Associated Molecular Patterns (DAMPs) in plasma, many of which are made of nucleic acids. DAMPs then bind leukocytes and trigger NETosis (Neutrophil Extracellular Traps), the release of nuclear material coated with proteolytic enzymes, which ultimately promotes remote lung injury and acute respiratory distress syndrome (ARDS).

Considering that many DAMPs and all NETs are made of nucleic acids, we hypothesize that dornase alfa, a commercially available recombinant desoxyribonuclease (DNAse) could reduce DAMPs and NETs-induced lung injury in severe trauma patients under mechanical ventilation in the intensive care unit (ICU).

The primary objective is to demonstrate a reduction in the incidence of moderate to severe ARDS in severe trauma patients during the first seven ICU days from 45% to 30% by providing aerosolized dornase alfa once during the first two consecutive ICU days and compared to equivalent provision of placebo (NaCl 0,9%).

The secondary objectives are to demonstrate, by using aerosolized dornase alfa compared to placebo:

an improvement in static lung compliance
a reduction in mechanical ventilation duration / an increase in ventilation-free ICU days
a reduction in the length of ICU stay
a reduction in the hospital length of stay
a reduction in multi-organ failure
a reduction in ventilator-associated pneumonia (VAP)
a reduction in mortality at day 28

Condition or Disease	Intervention/Treatment	Phase
Multiple Trauma Respiratory Distress Syndrome, Adult	Drug: Dornase Alfa Inhalant Solution [Pulmozyme] Drug: Placebos	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

500 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Prospective, Randomized Multicenter, Double Blind Clinical Trial Comparing Inhaled Dornase Alfa and Its Placebo to Reduce the Incidence of Moderate to Severe ARDS in Ventilated Trauma Patients in the Intensive Care Unit

Actual Study Start Date :

Mar 4, 2019

Anticipated Primary Completion Date :

Sep 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dornase alfa Dornase alfa (Pulmozyme®, Roche 2500U, 2,5mL) given by aerosol in the respiratory circuit (Aerogen solo®) within 6h at day 1 and 24 hours after on day 2.	Drug: Dornase Alfa Inhalant Solution [Pulmozyme] Dornase alfa (Pulmozyme®, Roche 2500U, 2,5mL) given by aerosol in the respiratory circuit (Aerogen solo®) within 6h at day 1 and 24 hours after on day 2.
Placebo Comparator: Placebo NaCl 0,9%, given by aerosol in the respiratory circuit within 6h at day 1 and 24 hours after on day 2.	Drug: Placebos NaCl 0,9%, given by aerosol in the respiratory circuit within 6h at day 1 and 24 hours after on day 2.

Arm

Intervention/Treatment

Experimental: Dornase alfa

Dornase alfa (Pulmozyme®, Roche 2500U, 2,5mL) given by aerosol in the respiratory circuit (Aerogen solo®) within 6h at day 1 and 24 hours after on day 2.

Drug: Dornase Alfa Inhalant Solution [Pulmozyme]

Dornase alfa (Pulmozyme®, Roche 2500U, 2,5mL) given by aerosol in the respiratory circuit (Aerogen solo®) within 6h at day 1 and 24 hours after on day 2.

Placebo Comparator: Placebo

NaCl 0,9%, given by aerosol in the respiratory circuit within 6h at day 1 and 24 hours after on day 2.

Drug: Placebos

NaCl 0,9%, given by aerosol in the respiratory circuit within 6h at day 1 and 24 hours after on day 2.

Outcome Measures

Primary Outcome Measures

The primary endpoint is the incidence of moderate to severe ARDS (PaO2/FiO2 < 200, according to the Berlin definition [ARDS definition task force et al. JAMA 2015; 307(23): 2526-2533]) in severe trauma patients (Injury Severity Score > 15). [Day 0 to Day 7]

Secondary Outcome Measures

Static lung compliance [mL/cmH2O] [Day 0 to Day 7]
Duration of mechanical ventilation [hours] [Day 0 to Day 7]
Length of ICU stay [hours] [Day 0 to Day 7]
Length of stay in the hospital [days] [Day 0 to Day 7]
Incidence of multi-organ failure [Day 0 to Day 7]
according SOFA (Sepsis-related Organ Failure Assessment) to quantify organ dysfunction
Incidence of Ventilator-Associated Pneumonia (VAP) [Day 0 to Day 7]
Mortality on day 28 [Day 28]