Inhaled Dornase Alpha to Reduce Respiratory Failure After Severe Trauma

Respiratory Distress Syndrome, Adult Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03368092
• Other study ID #: 6998
• Status: Recruiting
• Phase: Phase 3
• Start date: March 4, 2019
• Est. completion date: December 1, 2024

Study information

• Verified date: August 2023
• Source: University Hospital, Strasbourg, France
• Contact: Julien POTTECHER, MD
• Phone: +33 388127095
• Email: julien.pottecher[@]chru-strasbourg.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: December 1, 2024
• Est. primary completion date: September 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Lung Injury
• Multiple Trauma
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Wounds and Injuries

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.
• Placebos
NaCl 0,9%, given by aerosol in the respiratory circuit within 6h at day 1 and 24 hours after on day 2.

Locations

Country	Name	City	State
France	University Hospital, Strasbourg, france	Strasbourg

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Strasbourg, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).		Day 0 to Day 7
Secondary	Static lung compliance [mL/cmH2O]		Day 0 to Day 7
Secondary	Duration of mechanical ventilation [hours]		Day 0 to Day 7
Secondary	Length of ICU stay [hours]		Day 0 to Day 7
Secondary	Length of stay in the hospital [days]		Day 0 to Day 7
Secondary	Incidence of multi-organ failure	according SOFA (Sepsis-related Organ Failure Assessment) to quantify organ dysfunction	Day 0 to Day 7
Secondary	Incidence of Ventilator-Associated Pneumonia (VAP)		Day 0 to Day 7
Secondary	Mortality on day 28		Day 28