Inhaled Dornase Alpha to Reduce Respiratory Failure After Severe Trauma (TRAUMADORNASE)
Primary Purpose
Multiple Trauma, Respiratory Distress Syndrome, Adult
Status
Recruiting
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Dornase Alfa Inhalant Solution [Pulmozyme]
Placebos
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Trauma focused on measuring severe trauma, acute respiratory distress syndrome, damage-associated molecular patterns, neutrophil extracellular traps, dornase alfa
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
Sites / Locations
- University Hospital, Strasbourg, franceRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Dornase alfa
Placebo
Arm Description
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.
NaCl 0,9%, given by aerosol in the respiratory circuit within 6h at day 1 and 24 hours after on day 2.
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
Static lung compliance [mL/cmH2O]
Duration of mechanical ventilation [hours]
Length of ICU stay [hours]
Length of stay in the hospital [days]
Incidence of multi-organ failure
according SOFA (Sepsis-related Organ Failure Assessment) to quantify organ dysfunction
Incidence of Ventilator-Associated Pneumonia (VAP)
Mortality on day 28
Full Information
NCT ID
NCT03368092
First Posted
December 4, 2017
Last Updated
August 10, 2023
Sponsor
University Hospital, Strasbourg, France
1. Study Identification
Unique Protocol Identification Number
NCT03368092
Brief Title
Inhaled Dornase Alpha to Reduce Respiratory Failure After Severe Trauma
Acronym
TRAUMADORNASE
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 4, 2019 (Actual)
Primary Completion Date
September 1, 2024 (Anticipated)
Study Completion Date
December 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Strasbourg, France
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Trauma, Respiratory Distress Syndrome, Adult
Keywords
severe trauma, acute respiratory distress syndrome, damage-associated molecular patterns, neutrophil extracellular traps, dornase alfa
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
500 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dornase alfa
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
NaCl 0,9%, given by aerosol in the respiratory circuit within 6h at day 1 and 24 hours after on day 2.
Intervention Type
Drug
Intervention Name(s)
Dornase Alfa Inhalant Solution [Pulmozyme]
Intervention Description
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 Type
Drug
Intervention Name(s)
Placebos
Intervention Description
NaCl 0,9%, given by aerosol in the respiratory circuit within 6h at day 1 and 24 hours after on day 2.
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
Static lung compliance [mL/cmH2O]
Time Frame
Day 0 to Day 7
Title
Duration of mechanical ventilation [hours]
Time Frame
Day 0 to Day 7
Title
Length of ICU stay [hours]
Time Frame
Day 0 to Day 7
Title
Length of stay in the hospital [days]
Time Frame
Day 0 to Day 7
Title
Incidence of multi-organ failure
Description
according SOFA (Sepsis-related Organ Failure Assessment) to quantify organ dysfunction
Time Frame
Day 0 to Day 7
Title
Incidence of Ventilator-Associated Pneumonia (VAP)
Time Frame
Day 0 to Day 7
Title
Mortality on day 28
Time Frame
Day 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Julien POTTECHER, MD
Phone
+33 388127095
Email
julien.pottecher@chru-strasbourg.fr
Facility Information:
Facility Name
University Hospital, Strasbourg, france
City
Strasbourg
ZIP/Postal Code
67000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julien Pottecher, MD
Phone
03 88 12 70 95
Email
julien.pottecher@chru-strasbourg.fr
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
32183886
Citation
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.
Results Reference
derived
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Inhaled Dornase Alpha to Reduce Respiratory Failure After Severe Trauma
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