Clinical trial NCT00188058: Comparison of 2 Strategies of Adjustment of Mechanical Ventilation in Patients With Acute Respiratory Distress Syndrome
Official title: Comparison of Two Strategies for Setting Positive End-Expiratory Pressure in Acute Lung Injury/ Acute Respiratory Distress Syndrome (ExPress Study).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Respiratory Distress Syndrome
Acute Lung Injury
Keywords: Acute respiratory distress syndrome
Positive end-expiratory pressure
Acute lung injury
Mechanical ventilation
Randomized controlled trial
Lead sponsor: University Hospital, Angers
Sponsor class: OTHER_GOV
Collaborators: name: Ministry of Health, France
First posted: 2005-09-16
Enrollment: 768
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 aim of this multicenter randomized controlled trial is to compare the impact on mortality of patients mechanically ventilated for acute lung injury or acute respiratory distress syndrome of two strategies for setting end-expiratory pressure.

Detailed description: Most patients suffering from acute lung injury or acute respiratory distress syndrome require mechanical ventilation. In this setting, positive end-expiratory pressure is used to improve arterial oxygenation. While the beneficial effect on clinical outcome of using low tidal volume is clearly proven, the best way to titrate PEEP is not known. Higher PEEP levels may better improve oxygenation and reduce ventilator-induced lung injury by reducing end-expiratory alveolar collapse but may also cause circulatory depression and aggravate lung injury from end-inspiratory overdistension. This trial compares the impact on outcome of two strategies for setting PEEP. In the "minimal alveolar distension" arm, PEEP is set for a total PEEP (PEEP + intrinsic PEEP) between 5 and 9 cm H20). In the "maximal alveolar recruitment" arm, PEEP is set for a plateau pressure between 28 and 30 cm H20. A tidal volume of 6 ml/kg predicted body weight is used in the two arms. The goals for arterial oxygenation and PaCO2 are the same in the two arms.

Eligibility criteria: Inclusion Criteria:

* Mechanical ventilation through an endotracheal tube
* Bilateral infiltrates consistent with pulmonary edema
* PaO2/FiO2 \< 300 mmHg
* No clinical evidence of left atrial hypertension. If measured, pulmonary artery occlusion pressure \< 18 mmHg
* Criteria 1, 2 et 3 jointly present for less than 48 hours
* Written informed consent obtained from the patient or surrogate

Exclusion Criteria:

* Age \< 18 years
* Pregnancy
* Expected duration of mechanical ventilation through an endotracheal tube \< 48 hours
* Participation in other trials within the previous 30 days
* Increased intracranial pressure
* Severe chronic respiratory disease
* Morbid obesity (weight \> 1kg/cm)
* Sickle cell disease
* Bone marrow transplant or chemotherapy-induced neutropenia
* Extended burns (\> 30 % total body surface area)
* Severe chronic liver disease (Child-Pugh score C)
* Pneumothorax

Primary outcomes:
measure: Mortality at 28 days
timeFrame: day 28
Secondary outcomes:
measure: Mortality at 60 days
timeFrame: day 60
measure: In hospital mortality
timeFrame: day 60
measure: Ventilator free Days through day 28
timeFrame: day 28
measure: Number of new organ failure before day 28
timeFrame: day 28
measure: Proportion of patients alive and unassisted breathing at 28 days
timeFrame: day 28
measure: Number of patients with pneumothorax
timeFrame: day 28
measure: Number of days alive between the first positive "potential weanability test" and day 28
timeFrame: day 28
Other outcomes:
Locations:
city: Aix en Provence
country: France
facility: General Hospital of Aix en Provence
city: Amiens
country: France
facility: South Hospital of Amiens
city: Amiens
country: France
facility: University Hospital of Amiens
city: Angers
country: France
facility: University Hospital of Angers
city: Angers
country: France
facility: University Hospital of Angers
city: Argenteuil
country: France
facility: Victor Dupouy Hospital
city: Arras
country: France
facility: General Hospital of Arras
city: Aulnay Sous Bois
country: France
facility: Robert Ballanger Hospital
city: Avignon
country: France
facility: General Hospital of Avignon
city: Beauvais
country: France
facility: Hospital of Beauvais
city: Bordeaux
country: France
facility: Saint André Hospital
city: Bordeaux
country: France
facility: University Hospital of Bordeaux
city: Brest
country: France
facility: Cavale Blanche Hospital
city: Brive
country: France
facility: Hospital of Brive
city: Creteil
country: France
facility: Henri Mondor Hospital
city: Créteil
country: France
facility: Henri Mondor Hospital
city: Dax
country: France
facility: Hospital of Dax
city: Dieppe
country: France
facility: Hospital of Dieppe
city: La Roche Sur Yon
country: France
facility: Departemental Hospital
city: Le Havre
country: France
facility: Jacques Monod Hospital
city: Le Kremlin Bicetre
country: France
facility: Le Kremlin Bicetre Hospital
city: Lens
country: France
facility: Docteur Schaffner Hospital
city: Lille
country: France
facility: University Hospital of Claude Huriez
city: Lyon
country: France
facility: Croix Rousse Hospital
city: Metz
country: France
facility: Bon Secours Hospital
city: Montpellier
country: France
facility: Saint Eloi Hospital
city: Nancy
country: France
facility: Hospital of Nancy
city: Nantes
country: France
facility: University Hospital of Hotel Dieu
city: Nimes
country: France
facility: University Hospital of Nimes
city: Nimes
country: France
facility: University Hospital of Nimes
city: Oloron Sainte Marie
country: France
facility: Oloron Sainte Marie Hospital
city: Orleans
country: France
facility: Regional Hospital of Orleans
city: Paris
country: France
facility: Bichat Claude Bernard Hospital
city: Paris
country: France
facility: University Hospital of Hôtel Dieu
city: Paris
country: France
facility: Hospital Group of Pitié - Salpêtrière
city: Paris
country: France
facility: Hospital group of Pitié-Salpêtrière
city: Paris
country: France
facility: European Hospital of Georges Pompidou
city: Poitiers
country: France
facility: University Hospital of Jean Bernard
city: Poitiers
country: France
facility: University Hospital of La Milètrie
city: Pontoise
country: France
facility: René Dubos Hospital
city: Rouen
country: France
facility: Charles Nicolle Hospital
city: Rouen
country: France
facility: University Hospital of Rouen
city: Saint Aubin Les Elbeuf
country: France
facility: Saint Aubin Les Elbeuf Hospital
city: Saint-etienne
country: France
facility: University Hospital of Bellevue
city: Soissons
country: France
facility: Hospital of Soissons
city: Strasbourg
country: France
facility: Hautepierre Hospital
city: Tourcoing
country: France
facility: Gustave Dron Hospital
Study officials:
affiliation: University Hospital of Angers
name: ALAIN MERCAT, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mercat A, Richard J, Brochard L. Comparison of two strategies for setting Peep in ALI/ARDS : EsPress Study.Intensive care med, 19th ESICM Annual Congress - Barcelona, Spain, 2006 Sep, Oral presentation 0365
citation: Diehl JL, Coolen N, Faisy C, Osman D, Prat G, Sebbane M, Nieszkowska A, Gervais C, Richard JC, Richecoeur J, Brochard L, Mercat A, Guerot E, Borgel D. Growth-arrest-specific 6 (GAS6) protein in ARDS patients: determination of plasma levels and influence of PEEP setting. Respir Care. 2013 Nov;58(11):1886-91. doi: 10.4187/respcare.02129. Epub 2013 Apr 9.
citation: Mercat A, Richard JC, Vielle B, Jaber S, Osman D, Diehl JL, Lefrant JY, Prat G, Richecoeur J, Nieszkowska A, Gervais C, Baudot J, Bouadma L, Brochard L; Expiratory Pressure (Express) Study Group. Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA. 2008 Feb 13;299(6):646-55. doi: 10.1001/jama.299.6.646.