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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 : September 28, 2020
Sponsor:
Information provided by (Responsible Party):
University Hospital, Strasbourg, France

Tracking Information
First Submitted Date  ICMJE December 4, 2017
First Posted Date  ICMJE December 11, 2017
Last Update Posted Date September 28, 2020
Actual Study Start Date  ICMJE March 4, 2019
Estimated Primary Completion Date October 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 8, 2017)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 11, 2017)
  • Static lung compliance [mL/cmH2O] [ Time Frame: Day 0 to Day 7 ]
  • Duration of mechanical ventilation [hours] [ Time Frame: Day 0 to Day 7 ]
  • Length of ICU stay [hours] [ Time Frame: Day 0 to Day 7 ]
  • Length of stay in the hospital [days] [ Time Frame: Day 0 to Day 7 ]
  • Incidence of multi-organ failure [ Time Frame: Day 0 to Day 7 ]
    according SOFA (Sepsis-related Organ Failure Assessment) to quantify organ dysfunction
  • Incidence of Ventilator-Associated Pneumonia (VAP) [ Time Frame: Day 0 to Day 7 ]
  • Mortality on day 28 [ Time Frame: Day 28 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 8, 2017)
  • Static lung compliance [mL/cmH2O] [ Time Frame: Day 0 to Day 7 ]
  • Duration of mechanical ventilation [hours] [ Time Frame: Day 0 to Day 7 ]
  • Length of ICU stay [hours] [ Time Frame: Day 0 to Day 7 ]
  • Length of stay in the hospital [days] [ Time Frame: Day 0 to Day 7 ]
  • Incidence of multi-organ failure [ Time Frame: Day 0 to Day 7 ]
    according SOFA to quantify organ dysfunction
  • Incidence of VAP (ATS and CDC definitions) [ Time Frame: Day 0 to Day 7 ]
    according to both the ATS [Am J Respir Crit Care Med 2005;171(4):388-416] and CDC [Klompas et al. New England J Med 2013 18; 368(16):1472-1475] definitions.
  • Mortality on day 28 [ Time Frame: Day 28 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Inhaled Dornase Alpha to Reduce Respiratory Failure After Severe Trauma
Official Title  ICMJE 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
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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Multiple Trauma
  • Respiratory Distress Syndrome, Adult
Intervention  ICMJE
  • 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.
  • Drug: Placebos
    NaCl 0,9%, given by aerosol in the respiratory circuit within 6h at day 1 and 24 hours after on day 2.
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Dornase Alfa Inhalant Solution [Pulmozyme]
  • 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.
    Intervention: Drug: Placebos
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 8, 2017)
500
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 1, 2022
Estimated Primary Completion Date October 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Julien POTTECHER, MD +33 388127095 julien.pottecher@chru-strasbourg.fr
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03368092
Other Study ID Numbers  ICMJE 6998
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University Hospital, Strasbourg, France
Study Sponsor  ICMJE University Hospital, Strasbourg, France
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account University Hospital, Strasbourg, France
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP