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

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

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

Study Overview

• Status: Recruiting
• Conditions: Multiple Trauma; Respiratory Distress Syndrome, Adult
• Intervention / Treatment: Drug: Dornase Alfa Inhalant Solution [Pulmozyme]; Drug: Placebos

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Julien POTTECHER, MD; Phone Number: +33 388127095; Email: julien.pottecher@chru-strasbourg.fr

Study Locations

• France
  • Strasbourg, France, 67000
    • Recruiting
    • University Hospital, Strasbourg, france
    • Contact: Julien Pottecher, MD; Phone Number: 03 88 12 70 95; Email: julien.pottecher@chru-strasbourg.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Measure Description	Time Frame
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	according SOFA (Sepsis-related Organ Failure Assessment) to quantify organ dysfunction	Day 0 to Day 7
Incidence of Ventilator-Associated Pneumonia (VAP)		Day 0 to Day 7
Mortality on day 28		Day 28

Collaborators and Investigators

• Sponsor: University Hospital, Strasbourg, France

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2019
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: December 4, 2017
• First Submitted That Met QC Criteria: December 8, 2017
• First Posted (Actual): December 11, 2017

Study Record Updates

• Last Update Posted (Actual): August 8, 2025
• Last Update Submitted That Met QC Criteria: August 4, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: severe trauma; neutrophil extracellular traps; acute respiratory distress syndrome; damage-associated molecular patterns; dornase alfa
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Lung Injury; Multiple Trauma; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Wounds and Injuries; Acute Lung Injury
• Other Study ID Numbers: 6998

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No