Safety and Efficacy Study of Depelestat in Acute Respiratory Distress Syndrome (ARDS) Patients

Inflammation Clinical Trial

Official title:

Phase IIA Multicenter 1 Week Treatment, Randomised, Double-Blind, Placebo Controlled Study of Depelestat in Patients Suffering From Acute Respiratory Distress Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00455767
• Other study ID #: DEB-EPIV-201
• Secondary ID: 2006-000756-41 (
• Status: Completed
• Phase: Phase 2
• First received: March 14, 2007
• Last updated: June 23, 2008
• Start date: July 2006
• Est. completion date: September 2007

Study information

• Verified date: June 2008
• Source: Debiopharm International SA
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and EnvironmentTunisia: Office of Pharmacies and MedicinesItaly: Ethics CommitteeSpain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: September 2007
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Fibrosis
• Inflammation
• Lung Disease
• Lung Diseases
• Pulmonary Fibrosis
• Respiration Disorders
• Respiratory Disorders
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Respiratory Tract Diseases
• Syndrome

Intervention

Drug:
• EPI-hNE4
I.V. injection of 1mg/kg Depelestat (EPI-hNE4) 3 times daily for 7 days
• Placebo
Placebo

Locations

Country	Name	City	State
France	Alain Mercat	Angers
France	Yves Castaing	Bordeaux
France	Laurent Brochard	Créteil Cedex
France	Jean-François Timsit	Grenoble Cedex 09
France	Claude Guerin	Lyon
France	Samir Jaber	Montpellier Cedex 05
France	Jean-Jacques Rouby	Paris
France	Jean-Daniel Chiche	Paris Cedex
France	Jean-Yves Fagon	Paris Cedex 15
France	Jean-Christophe Richard	Rouen Cedex
France	Jean-Michel Arnal	Toulon
Italy	Massimo Antonelli	Roma
Spain	Jordi Mancebo D.	Barcelona
Tunisia	Fekri Abroug	Monastir

Sponsors (1)

Lead Sponsor	Collaborator
Debiopharm International SA

Countries where clinical trial is conducted

France,  Italy,  Spain,  Tunisia, 

References & Publications (1)

Honoré 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Static compliance relative change from pre-treatment to last on treatment
Secondary	PCPIII and cytokines concentration, as well as neutrophil influx relative change in BAL fluid from pre-treatment to post-treatment

External Links

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