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

• ClinicalTrials.gov Identifier: NCT03368092
• Recruitment Status: Recruiting
• First Posted: December 11, 2017
• Last Update Posted: September 28, 2020
• Sponsor: University Hospital, Strasbourg, France
• Information provided by (Responsible Party): University Hospital, Strasbourg, France

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 (Clinical Trial)
• Estimated 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: March 4, 2019
• Estimated Primary Completion Date: October 1, 2022
• Estimated Study Completion Date: November 1, 2022

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.

Outcome Measures

Primary Outcome Measures :

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). [ Time Frame: Day 0 to Day 7 ]

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Julien POTTECHER, MD; +33 388127095; julien.pottecher@chru-strasbourg.fr

Locations

France

University Hospital, Strasbourg, france; Recruiting

Strasbourg, France, 67000

Contact: Julien Pottecher, MD 03 88 12 70 95 julien.pottecher@chru-strasbourg.fr

Sponsors and Collaborators

University Hospital, Strasbourg, France

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: University Hospital, Strasbourg, France
• ClinicalTrials.gov Identifier: NCT03368092
• Other Study ID Numbers: 6998
• First Posted: December 11, 2017
• Last Update Posted: September 28, 2020
• Last Verified: August 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Strasbourg, France:

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

Additional relevant MeSH terms:

Respiratory Distress Syndrome, Newborn; Respiratory Distress Syndrome, Adult; Acute Lung Injury; Wounds and Injuries; Multiple Trauma; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Lung Injury