Inhaled Dornase Alpha to Reduce Respiratory Failure After Severe Trauma

NCT03368092 | Recruiting Phase 3 DMC

• 1 other identifier: 6998
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 1

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

Conditions

Multiple Trauma; Respiratory Distress Syndrome, Adult

Keywords

severe trauma; acute respiratory distress syndrome; damage-associated molecular patterns; neutrophil extracellular traps; dornase alfa

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• 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

Study Arms (2)

Dornase alfa

EXPERIMENTAL

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]

Placebo

PLACEBO COMPARATOR

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

Drug: Placebos

Interventions

Dornase Alfa Inhalant Solution [Pulmozyme] DRUG

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.

Dornase alfa

Placebos DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Strasbourg, France: lead

Study Sites (1)

University Hospital, Strasbourg, france

Strasbourg, 67000, France

RECRUITING

Related Publications (1)

• Pottecher J, Noll E, Borel M, Audibert G, Gette S, Meyer C, Gaertner E, Legros V, Carapito R, Uring-Lambert B, Sauleau E, Land WG, Bahram S, Meyer A, Geny B, Diemunsch P. Protocol for TRAUMADORNASE: a prospective, randomized, multicentre, double-blinded, placebo-controlled clinical trial of aerosolized dornase alfa to reduce the incidence of moderate-to-severe hypoxaemia in ventilated trauma patients. Trials. 2020 Mar 18;21(1):274. doi: 10.1186/s13063-020-4141-6.

  PMID: 32183886 DERIVED

MeSH Terms

Conditions

Multiple Trauma; Respiratory Distress Syndrome; Wounds and Injuries

Interventions

dornase alfa

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Central Study Contacts

Julien POTTECHER, MD

CONTACT

+33 388127095; julien.pottecher@chru-strasbourg.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2017
• First Posted: December 11, 2017
• Study Start: March 4, 2019
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: August 8, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)