Inhaled Dornase Alpha to Reduce Respiratory Failure After Severe Trauma (TRAUMADORNASE)

University Hospital, Strasbourg, France

Status and phase: Enrolling; Phase 3

Conditions: Multiple Trauma; Respiratory Distress Syndrome, Adult

Treatments: Drug: Dornase Alfa Inhalant Solution [Pulmozyme]; Drug: Placebos

Study type: Interventional

Funder types: Other

Identifiers

NCT03368092

6998

Details and patient eligibility

About

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

Enrollment: 500 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult (>18) patient of either sex affiliated to the National Health Service

  • Severe trauma patient (either blunt or penetrating), Injury Severity Score > 15
  • Under mechanical ventilation for an expected duration > 48h
  • Admitted in the ICU
  • Signed informed consent from the patient's relative
  • Patient equipped with an indwelling arterial catheter

Exclusion criteria

• Pregnancy or breast feeding

  • Opposition from the patient or his/her relatives
  • Protected major (Guardianship)
  • Contraindication to the use of dornase alfa
  • Known intolerance to dornase alfa

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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500 participants in 2 patient groups, including a placebo group

Dornase alfa

Experimental group

Description:

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.

Treatment:

Drug: Dornase Alfa Inhalant Solution [Pulmozyme]

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebos