TRAUMADORNASE 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

2024-512034-14-00 Protocol 6998 Therapeutic confirmatory (Phase III) Ongoing, recruiting

Start 4 Mar 2019 · Status Ongoing, recruiting · 1 EU/EEA countries · 12 sites · Protocol 6998

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Ongoing, recruiting
Participants planned 500
Countries 1
Sites 12

severe trauma

To demonstrate the efficacy of early intratracheal administration of dornase alfa in reducing the incidence of moderate and severe acute respiratory distress syndrome (PaO2/FiO2 ratio ≤ 200 or SpO2/FiO2 ≤ 235 if SpO2 ≤ 97%) during the first 7 days post-traumatic in patients with severe trauma (ISS>15) and hospitalized…

Key facts

Sponsor
Les Hopitaux Universitaires De Strasbourg
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Respiratory Tract Diseases [C08]
Trial duration
4 Mar 2019 → ongoing
Decision date (initial)
2024-05-28
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes

External identifiers

EU CT number
2024-512034-14-00
EudraCT number
2018-000654-22
ClinicalTrials.gov
NCT03368092

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis, Efficacy

To demonstrate the efficacy of early intratracheal administration of
dornase alfa in reducing the incidence of moderate and severe acute
respiratory distress syndrome (PaO2/FiO2 ratio ≤ 200 or SpO2/FiO2 ≤ 235 if SpO2 ≤ 97%) during the first 7
days post-traumatic in patients with severe trauma (ISS>15) and
hospitalized in intensive care.

Secondary objectives 8

  1. Demonstrate the efficacy of early intratracheal administration of dornase alfa to reduce: the incidence of ventilation acquired pneumonia
  2. Demonstrate the efficacy of early intratracheal administration of dornase alfa to reduce: the impact of multi organ failure
  3. Demonstrate the efficacy of early intratracheal administration of dornase alfa to reduce: The incidence of minimal respiratory distress syndromes (200 < PaO2/FiO2 ≤ 300 or SpO2/FiO2 comprised between 235 and 315 [235 < PaO2/FiO2 ≤ 315] if SpO2 ≤ 97%)
  4. Demonstrate the efficacy of early intratracheal administration of dornase alfa to reduce: the duration of mechanical ventilation (hours)
  5. Demonstrate the efficacy of early intratracheal administration of dornase alfa to reduce: the length of intensive care unit stay (hours)
  6. Demonstrate the efficacy of early intratracheal administration of dornase alfa to reduce: the length of hospital stay
  7. Demonstrate the efficacy of early intratracheal administration of dornase alfa to reduce: the mortality on D30
  8. Assessment of the safety of administration of dornase alfa

Conditions and MedDRA coding

severe trauma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

  1. Adult (>18) patient of either sex affiliated to the National Health Service
  2. Severe trauma patient (either blunt or penetrating), Injury Severity Score > 15
  3. Under mechanical ventilation. Extubation of the patient within the first 48 hours is not a reason for leaving the study, as the investigational treatment can be administered in a similar manner to the extubated patient.
  4. Admitted in the ICU for less than 6 hours (or less than 18 hours after arrival at the hospital[de-shocking] in the case of prior surgery or embolization)
  5. Signed informed consent from the patient's relative or emergency procedure
  6. Patient equipped with an indwelling arterial catheter
  7. - For a woman of childbearing age, negative blood pregnancy test

Exclusion criteria 7

  1. Pregnancy or breast feeding
  2. Opposition from the patient or his/her relatives
  3. Protected major (Guardianship)
  4. Known intolerance to dornase alfa. Contraindication to the use of dornase alfa
  5. Ventilation by high frequency oscillations
  6. - Subject already included in an interventional study.
  7. - Treatment (current or previous) with dornase alfa

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Incidence of moderate to severe ARDS (PaO2/FiO2 ≤ 200 or SpO2/FiO2 ≤ 235 if SpO2 ≤ 97%), according to the 2024 global definition in severe trauma patients (Injury Severity Score > 15).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

PULMOZYME 2500 U/2,5 ml, solution pour inhalation par nébuliseur

PRD1750355 · Product

Active substance
Dornase Alfa
Pharmaceutical form
NEBULISER SOLUTION
Route of administration
INHALATION USE
Max daily dose
2500 IU international unit(s)
Max total dose
5000 IU international unit(s)
Max treatment duration
2 Day(s)
Authorisation status
Authorised
ATC code
R05CB13 — DORNASE ALFA (DESOXYRIBONUCLEASE)
Marketing authorisation
34009 364 674 8 4
MA holder
ROCHE
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Placebo 1

Sodium Chloride

SUB12581MIG · Substance

Active substance
Sodium Chloride
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INHALATION USE
Max daily dose
2.5 ml millilitre(s)
Max total dose
5 ml millilitre(s)
Max treatment duration
2 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Les Hopitaux Universitaires De Strasbourg

17 Total trials 11 Recruiting 3 Ended
Academic / Non-commercial
Sponsor organisation
Les Hopitaux Universitaires De Strasbourg
Address
1 Place De L Hopital, Cs 80426 Cs 80426
City
Strasbourg Cedex
Postcode
67091
Country
France

Scientific contact point

Organisation
Les Hopitaux Universitaires De Strasbourg
Contact name
POTTECHER Julien

Public contact point

Organisation
Les Hopitaux Universitaires De Strasbourg
Contact name
POTTECHER Julien

Locations

1 EU/EEA country · 12 investigational sites

By country

CountryMS statusPlanned subjectsSites
France Ongoing, recruiting 500 12
Rest of world — 0 —

Investigational sites

France

12 sites · Ongoing, recruiting
Assistance Publique Hopitaux De Paris
75, 47 Boulevard De L Hopital, 75651, Paris Cedex 13
CHRU De Nancy
54, 29 Avenue Du Mal De Lattre De Tassigny, 54000, Nancy
Centre Hospitalier Universitaire De Montpellier
34, 371 Avenue Du Doyen Gaston Giraud, 34091, Montpellier Cedex 5
Centre Hospitalier Universitaire De Lille
59, Avenue Du Professeur Emile Laine, 59037, Lille Cedex
Centre Hospitalier Universitaire Reims
51, 45 Rue Cognacq Jay, 51092, Reims Cedex
Centre Hospitalier Universitaire De Toulouse
31, 1 Place Du Docteur Joseph Baylac, 31300, Toulouse
University Hospital Of Clermont-Ferrand
63, 58 Rue Montalembert, 63003, Clermont Ferrand Cedex 1
Hospices Civils De Lyon
69, 165 Chemin Du Grand Revoyet, 69310, Pierre-Benite
Centre Hospitalier Regional De Marseille
13, 265 Chemin Des Bourrely, 13015, Marseille
Centre Hospitalier Universitaire De Toulouse
31, 1 Place Du Docteur Joseph Baylac, 31300, Toulouse
Centre Hospitalier Universitaire D'Angers
49, 4 Rue Larrey, 49100, Angers
Les Hopitaux Universitaires De Strasbourg
67, 1 Avenue Moliere, Bp 49, Strasbourg Cedex 2

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
France 2019-03-04 2019-03-04

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocol 6.1
Recruitment arrangements (for publication) K1_Recruitment arrangements_6998 1
Subject information and informed consent form (for publication) L1_ SIS and ICF_Attestation inclusion - urgence vitale 2.1
Subject information and informed consent form (for publication) L1_ SIS and ICF_Majeur 2.1
Subject information and informed consent form (for publication) L1_ SIS and ICF_Urgence - poursuite recherche - accord patient 2.1
Subject information and informed consent form (for publication) L1_ SIS and ICF_Urgence accord famille-personne de confiance 2.1
Subject information and informed consent form (for publication) L1_ SIS and ICF_Urgence vitale immediate - poursuite recherche - accord patient 2.1
Subject information and informed consent form (for publication) L1_ SIS and ICF_Urgence vitale immediate poursuite recherche-accord famille-personne de confiance 2.1
Summary of Product Characteristics (SmPC) (for publication) G2_RCP Pulmozyme 1
Synopsis of the protocol (for publication) D1_Protocol synopsis_Fr 6.1

Application history

3 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-05-02 France Acceptable
2024-05-27
 2024-05-28
2 SUBSTANTIAL MODIFICATION SM-1 2024-11-21 France Acceptable
2025-01-19
 2025-01-20
3 SUBSTANTIAL MODIFICATION SM-2 2025-11-24 France Acceptable
2026-02-02
 2026-02-02

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