Clinical trial NCT00455767: Safety and Efficacy Study of Depelestat in Acute Respiratory Distress Syndrome (ARDS) Patients
Official title: Phase IIA Multicenter 1 Week Treatment, Randomised, Double-Blind, Placebo Controlled Study of Depelestat in Patients Suffering From Acute Respiratory Distress Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Fibrosis
Lung Disease
Respiratory Disorders
Respiratory Distress Syndrome, Adult
Acute Respiratory Distress Syndrome
Pulmonary Fibrosis
Inflammation
Keywords: persistent ARDS
alveolar inflammation
early pulmonary fibrosis
mechanichal ventilation
P/V curve
Static compliance
elastase activity
inhibitor of Human Neutrophil Elastase
Lead sponsor: Debiopharm International SA
Sponsor class: INDUSTRY
First posted: 2007-04-04
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study is aimed to assess safety of Depelestat treatment, as well as efficacy on prevention and treatment of alveolar inflammation in early pulmonary fibrosis in patients suffering from persistent Acute Respiratory Distress Syndrome.

Detailed description: This is a multicenter, randomised, double-blind, parallel groups, placebo-controlled, 1 week treatment of Depelestat, in patients suffering from persistent ARDS.

Patients admitted in the intensive care unit presenting ARDS criteria persistent for 12 hours to 24 hours, will be randomly assigned to the treatment by Depelestat or placebo, after a pre-treatment period as short as possible with a maximum of 48 hours since ARDS criteria are met. During the pre-treatment period, the informed consent will be obtained from the legally authorized relative of the patient, and pre-treatment biological and functional examinations will be performed, particularly blood samples and BAL for biological parameters measurement, and ventilatory mechanics, for assessment of static compliance of the respiratory system.

After the pre-treatment period, the patient will receive treatment by Depelestat or placebo during 7 days, or until extubation of the patient if this occurs before 7 days of treatment. During this treatment period, the patient will be submitted to a daily measurement of static compliance of the respiratory system, as long as the patient adaptation to 24 hours after mechanical ventilation allows the procedure, and at 96 initiation of treatment, to a blood sampling and a bronchoalveolar lavage for several biological parameters assessment.

On the first and last day of administration, blood will be also collected for pharmacokinetic evaluation.

During the post-treatment period, the patient will be submitted, at 48 h ± 24 h after the end of treatment, to a blood sampling and a BAL (this BAL is not performed when contraindication criteria are present, if the patient is already extubated, and in case of planed extubation during the subsequent 24 hours) for several biological parameters assessment, and a daily measurement of static compliance as long as the patient adaptation to mechanical ventilation allows the procedure. Patients already extubated will not be submitted to BAL nor to static compliance measurements.

After the end of the treatment, patients will be followed daily for 28 days after the diagnostic of ARDS, or until death whichever occurred first.

The duration of the study for each survivor patient will be 28 days. Survivors to day 28 will be contacted monthly to assess survival and fill in a QOL questionnaire on days 60 and 90.

Eligibility criteria: Inclusion Criteria:

* Patients suffering from persistent ARDS as defined by the American and European Consensus Conference on ARDS, 1994

Exclusion Criteria:

* ARDS secondary to traumatism
* Pulmonary emphysema on pulmonary fibrosis
* Lung pneumocystosis
* Bronchopleural fistula
* Systemic corticosteroid treatment for more than 2 weeks before inclusion
* Severe organ disease excepted renal

Primary outcomes:
measure: Static compliance relative change from pre-treatment to last on treatment
Secondary outcomes:
measure: PCPIII and cytokines concentration, as well as neutrophil influx relative change in BAL fluid from pre-treatment to post-treatment
Other outcomes:
Locations:
city: Angers
country: France
facility: Alain Mercat
city: Bordeaux
country: France
facility: Yves Castaing
city: Créteil Cedex
country: France
facility: Laurent Brochard
city: Grenoble Cedex 09
country: France
facility: Jean-François Timsit
city: Lyon
country: France
facility: Claude Guerin
city: Montpellier Cedex 05
country: France
facility: Samir Jaber
city: Paris Cedex 15
country: France
facility: Jean-Yves Fagon
city: Paris Cedex
country: France
facility: Jean-Daniel Chiche
city: Paris
country: France
facility: Jean-Jacques Rouby
city: Rouen Cedex
country: France
facility: Jean-Christophe Richard
city: Toulon
country: France
facility: Jean-Michel Arnal
city: Roma
country: Italy
facility: Massimo Antonelli
city: Barcelona
country: Spain
facility: Jordi Mancebo D.
city: Monastir
country: Tunisia
facility: Fekri Abroug
Study officials:
affiliation: Debiopharm SA
name: François Saudubray, MD
role: STUDY_DIRECTOR
References:
citation: Honore S, Attalah HL, Azoulay E, Soussy CJ, Saudubray F, Harf A, Brochard L, Delclaux C. Beneficial effect of an inhibitor of leukocyte elastase (EPI-hNE-4) in presence of repeated lung injuries. Shock. 2004 Aug;22(2):131-6. doi: 10.1097/01.shk.0000126861.77543.d0.