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

Tracking Information

• First Submitted Date: December 4, 2017
• First Posted Date: December 11, 2017
• Last Update Posted Date: September 28, 2020
• Actual Study Start Date: March 4, 2019
• Estimated Primary Completion Date: October 1, 2022 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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 (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: Inhaled Dornase Alpha to Reduce Respiratory Failure After Severe Trauma
• 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

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: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Multiple Trauma
• Respiratory Distress Syndrome, Adult

Intervention

• 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

• 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 8, 2017): 500
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 1, 2022
• Estimated Primary Completion Date: October 1, 2022 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: France

Administrative Information

• NCT Number: NCT03368092
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Responsible Party: University Hospital, Strasbourg, France
• Study Sponsor: University Hospital, Strasbourg, France
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: University Hospital, Strasbourg, France
• Verification Date: August 2020