Study of a Strategy to Prevent Oversedation in Intensive Care Patients Under Mechanical Ventilation (AWARE)

This study has been completed.
Sponsor:
Collaborators:
Clinical Research Committee, French Society for Intensive Care, France
University Hospital, Tours
Information provided by (Responsible Party):
French Society for Intensive Care
ClinicalTrials.gov Identifier:
NCT01617265
First received: June 6, 2012
Last updated: August 25, 2015
Last verified: August 2015
  Purpose

The purpose of the present study is to determine whether administration of sedation according to a strategy including a bundle of measures to prevent oversedation is associated with a reduction in mortality of intensive care unit patients requiring mechanical ventilation, compared to administration of sedation according to usual practices.


Condition Intervention
ICU Patients Requiring Invasive Mechanical Ventilation
Procedure: Clinical Procedure to Prevent Oversedation
Procedure: Usual sedation practice

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Prevention of Oversedation in Intensive Care Patients Under Mechanical Ventilation : the AWARE Multicentric Randomized Trial

Further study details as provided by French Society for Intensive Care:

Primary Outcome Measures:
  • Day-90 mortality [ Time Frame: Mortality at Day 90 after randomization ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Mortality at Day 28 [ Time Frame: at day 28 ] [ Designated as safety issue: No ]
  • Hospital mortality [ Time Frame: at hospital discharge, up to day 90 ] [ Designated as safety issue: No ]
  • 1-yr mortality [ Time Frame: at 1 yr ] [ Designated as safety issue: No ]
  • Mechanical ventilation duration [ Time Frame: From onset of mechanical ventilation to day 28 ] [ Designated as safety issue: No ]
  • Days alive with no mechanical ventilation [ Time Frame: From ICU admission up to day 28 ] [ Designated as safety issue: No ]
  • Occurence of ventilator-associated pneumonia [ Time Frame: During mechanical ventilation duration, up to day 28 ] [ Designated as safety issue: No ]
  • Use of non-invasive ventilation after extubation [ Time Frame: From extubation to ICU discharge up to day 28 ] [ Designated as safety issue: No ]
  • Duration of ICU stay [ Time Frame: From ICU admission to ICU discharge or death in ICU, up to day 90 ] [ Designated as safety issue: No ]
  • ICU confusion [ Time Frame: From Day 1 to 7, and at day 14, 21 and 28 ] [ Designated as safety issue: No ]
    Number of patients alive, awaken, and free of ICU-delirium assessed on the CAM-ICU

  • Proximal muscle weakness [ Time Frame: from day 1 to 7, and at day 14, 21 and 28 ] [ Designated as safety issue: No ]
    Number of patients alive, awaken, cooperative and free of proximal muscle weakness

  • Functional, cognitive and psychological status [ Time Frame: At day 90 and 1 year ] [ Designated as safety issue: No ]
    Functional status (measured on the Barthel scale), depression (measured on the Hospital Anxiety & Depression Scale), Posttraumatic stress disorder (measured on the Impact of Event Scale), Quality of Life (measured on the SF-36) and patient living location

  • Time to weaning onset [ Time Frame: Time from mechancial ventilation initiation to first spontaneous breathing trial, up to day 28 ] [ Designated as safety issue: No ]
  • Number of patients requiring tracheotomy [ Time Frame: During ICU stay, up to day 28 ] [ Designated as safety issue: No ]
  • First sitting in chair [ Time Frame: During ICU stay, up to day 28 ] [ Designated as safety issue: No ]

Enrollment: 1180
Study Start Date: June 2012
Study Completion Date: June 2015
Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Prevention of oversedation group
In this arm sedation and analgesia will be administered according to a bundle of measures aimed at limiting oversedation, including repeated assessment of patients needs and graduate therapeutic response to control pain, discomfort, poor synchrony with the ventilator and agitation. The therapeutic options include non hypnotic anxiolytics, repeated intravenous (IV) hypnotics boluses, short-duration (6 hours) IV hypnotics infusion and round the clock IV hypnotics infusion.
Procedure: Clinical Procedure to Prevent Oversedation
Sedation and analgesia will be administered according to a bundle of measures aimed at limiting oversedation, including repeated assessment of patients needs and graduate therapeutic response to control pain, discomfort, poor synchrony with the ventilator and agitation. The therapeutic options include non hypnotic anxiolytics, repeated IV hypnotics boluses, short-duration (6 hours) IV hypnotics infusion and round the clock IV hypnotics infusion.
Active Comparator: Conventional sedation group
In this arm, sedation will be administered according to the usual practices in each participating center.
Procedure: Usual sedation practice
Sedation and analgesia will be administered according to the usual practices in each participating center.

Detailed Description:

In intensive care unit (ICU) patients receiving mechanical ventilation (MV), potent hypnotics and morphinics are frequently administered to increase synchrony with the ventilator, control agitation and decrease discomfort and pain due to the tracheal tube, bed ridding, painful condition and diagnostic or therapeutic procedures.

However, administration sedatives or morphinics is often excessive and may result in deep and prolonged alteration of consciousness, delayed weaning from MV and prolonged MV. and exposes the patient to a higher risk of ventilator-associated pneumonia, ICU delirium and neuromuscular weakness at awakening.

The present randomized multicenter study will compare the day-90 mortality of a group of patients receiving conventional sedation to the mortality of a group of patients receiving sedation administered according to an algorithm aimed to prevent oversedation to the mortality. The algorithm is built on a graduate therapeutic response to increasingly intense symptoms of discomfort, pain, ventilator dyssynchrony and agitation, and includes the use of analgesics, non hypnotic benzodiazepines, neuroleptics, repeated intravenous (IV) boluses of hypnotics and short duration (6 hours) IV hypnotic infusions.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18 and older
  • Admission to ICU with expected mechanical ventilation duration > 48 hrs
  • Mechanical ventilation in ICU for less than 12 hours
  • Information provided to the patient or proxy

Exclusion Criteria:

  • ICU Admission after cardiac arrest
  • Acute or chronic neuromuscular disease
  • Tracheotomy on ICU admission
  • Acute cerebral injury with intracranial hypertension requiring continuous IV sedation with or without neuromuscular blockade
  • Status epilepticus
  • Treatment withdrawal decision
  • Pregnancy, breast feeding
  • Concurrent participation in another interventional study requiring a change in usual practice of sedation or mechanical ventilation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01617265

Locations
France
Hôpital Saint-Esprit
Agen, France, 47923
CHU d'Angers
Angers, France, 49000
Hopital Privé d'Antony
Antony, France, 92166
CH d'Argenteuil
Argenteuil, France, 95100
CH Germon et Gauthier
Beuvry, France, 62408
Hopital Avicenne
Bobigny, France, 93000
Hopital St-Andre
Bordeaux, France, 33075
Hopital Ambroise Pare
Boulogne Billancourt, France, 92100
CHRU de la Cavale Blanche
Brest, France, 29609
Hopital Antoine Beclere
Clamart, France, 92140
CH Sud Francilien
Corbeil-Essones, France, 91106
CHU Henri Mondor
Creteil, France, 94010
Hopital Raymond Poincare
Garches, France, 92380
CHD Les Oudairies
la Roche sur Yon, France, 85925
CH de Versailles
Le Chesnay, France, 78157
CHU Kremlin-Bicetre
Le Kremelin-Bicetre, France, 94270
Hopital Roger Salengro
Lille, France, 59037
Groupe Hospitalier Edouard Herriot
Lyon, France, 69437
CH St-Joseph St-Luc
Lyon, France, 69000
Hopital de la Timone
Marseille, France, 13385
CHU Marseille Hopital Nord
Marseilles, France, 13015
CH de Meaux
Meaux, France, 77104
Hopital Notre-Dame de Bon Secours
Metz, France, 57038
CH Princesse Grace
Monaco, France, 98012
GHIRM
Montfermeil, France, 93370
Hopital Laennec
Nantes, France, 44035
Hopital l'Archet
Nice, France, 06202
CHR d'Orléans Hopital la Source
Orléans, France, 45067
Hopital St Louis
Paris, France, 75010
Hopital Tenon
Paris, France, 75020
Institut Mutualiste Montsouris
Paris, France, 75014
CH Francois Miterrand
Pau, France, 64046
CH Poissy
Poissy, France, 78300
CH de Pontoise
Pontoise, France, 95303
CH de la Région d'Annecy
Pringy, France, 74374
CH Leon Binet
Provins, France, 77488
CH de St-Brieuc
St-Brieuc, France, 22027
Hopital Delafontaine
St-Denis, France, 93200
CH de St-Malo
St-Malo, France, 35403
HIA Béjin
St-Mande, France, 94160
CHRU Bretonneau
Tours, France, 37044
Hopital Jean Bernard
Valenciennes, France, 59322
Institut Gustave Roussy
Villejuif, France, 94805
Sponsors and Collaborators
French Society for Intensive Care
Clinical Research Committee, French Society for Intensive Care, France
University Hospital, Tours
Investigators
Study Chair: Bernard DE JONGHE, MD French Society of Intensive Care
  More Information

Publications:

Responsible Party: French Society for Intensive Care
ClinicalTrials.gov Identifier: NCT01617265     History of Changes
Other Study ID Numbers: SRLF-TG-1-AWARE, 2011-004246-18
Study First Received: June 6, 2012
Last Updated: August 25, 2015
Health Authority: France: Comité de Protection des Personnes (CPP) Sud-Est 6
France: Commission Nationale Informatique et Libertés (CNIL)
France: Comité Consultatif sur le Traitement de l'Information en matière de Recherche dans le domaine de la Santé (CCTIRS)

Keywords provided by French Society for Intensive Care:
intensive care
mechanical ventilation
sedatives
morphinics
oversedation
mortality
midazolam
propofol
pain
agitation

ClinicalTrials.gov processed this record on August 31, 2015