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

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ClinicalTrials.gov Identifier: NCT03368092
Recruitment Status : Recruiting
First Posted : December 11, 2017
Last Update Posted : August 21, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospital, Strasbourg, France

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

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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, 2021
Estimated Study Completion Date : October 1, 2021


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.




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 ]


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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03368092


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

Locations
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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

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Responsible Party: University Hospital, Strasbourg, France
ClinicalTrials.gov Identifier: NCT03368092    
Other Study ID Numbers: 6998
First Posted: December 11, 2017    Key Record Dates
Last Update Posted: August 21, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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