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

• ClinicalTrials.gov Identifier: NCT01617265
• Recruitment Status: Completed
• First Posted: June 12, 2012
• Last Update Posted: August 26, 2015
• Sponsor: French Society for Intensive Care
• Collaborator: University Hospital, Tours
• Information provided by (Responsible Party): French Society for Intensive Care

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
ICU Patients Requiring Invasive Mechanical Ventilation	Procedure: Clinical Procedure to Prevent Oversedation; Procedure: Usual sedation practice	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1180 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Prevention of Oversedation in Intensive Care Patients Under Mechanical Ventilation : the AWARE Multicentric Randomized Trial
• Study Start Date: June 2012
• Actual Primary Completion Date: June 2015
• Actual Study Completion Date: June 2015

Arms and Interventions

Arm	Intervention/treatment
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.

Outcome Measures

Primary Outcome Measures :

1. Day-90 mortality [ Time Frame: Mortality at Day 90 after randomization ]

Secondary Outcome Measures :

1. Mortality at Day 28 [ Time Frame: at day 28 ]
2. Hospital mortality [ Time Frame: at hospital discharge, up to day 90 ]
3. 1-yr mortality [ Time Frame: at 1 yr ]
4. Mechanical ventilation duration [ Time Frame: From onset of mechanical ventilation to day 28 ]
5. Days alive with no mechanical ventilation [ Time Frame: From ICU admission up to day 28 ]
6. Occurence of ventilator-associated pneumonia [ Time Frame: During mechanical ventilation duration, up to day 28 ]
7. Use of non-invasive ventilation after extubation [ Time Frame: From extubation to ICU discharge up to day 28 ]
8. Duration of ICU stay [ Time Frame: From ICU admission to ICU discharge or death in ICU, up to day 90 ]
9. ICU confusion [ Time Frame: From Day 1 to 7, and at day 14, 21 and 28 ]
   Number of patients alive, awaken, and free of ICU-delirium assessed on the CAM-ICU
10. Proximal muscle weakness [ Time Frame: from day 1 to 7, and at day 14, 21 and 28 ]
    Number of patients alive, awaken, cooperative and free of proximal muscle weakness
11. Functional, cognitive and psychological status [ Time Frame: At day 90 and 1 year ]
    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
12. Time to weaning onset [ Time Frame: Time from mechancial ventilation initiation to first spontaneous breathing trial, up to day 28 ]
13. Number of patients requiring tracheotomy [ Time Frame: During ICU stay, up to day 28 ]
14. First sitting in chair [ Time Frame: During ICU stay, up to day 28 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

CH St-Joseph St-Luc

Lyon, France, 69000

Groupe Hospitalier Edouard Herriot

Lyon, France, 69437

CHU Marseille Hopital Nord

Marseilles, France, 13015

Hopital de la Timone

Marseille, France, 13385

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

Institut Mutualiste Montsouris

Paris, France, 75014

Hopital Tenon

Paris, France, 75020

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

University Hospital, Tours

Investigators

• Study Chair: Bernard DE JONGHE, MD; French Society of Intensive Care

More Information

Publications:

Payen JF, Chanques G, Mantz J, Hercule C, Auriant I, Leguillou JL, Binhas M, Genty C, Rolland C, Bosson JL. Current practices in sedation and analgesia for mechanically ventilated critically ill patients: a prospective multicenter patient-based study. Anesthesiology. 2007 Apr;106(4):687-95; quiz 891-2.

Kollef MH, Levy NT, Ahrens TS, Schaiff R, Prentice D, Sherman G. The use of continuous i.v. sedation is associated with prolongation of mechanical ventilation. Chest. 1998 Aug;114(2):541-8.

Constantin JM, Chanques G, De Jonghe B, Sanchez P, Mantz J, Payen JF, Sztark F, Richebé P, Lagneau F, Capdevila X, Bazin JE, Lefrant JY. [Current use of sedation and analgesia: 218 resuscitations in France services practices survey]. Ann Fr Anesth Reanim. 2010 May;29(5):339-46. doi: 10.1016/j.annfar.2010.01.014. Epub 2010 Apr 13. French.

Brook AD, Ahrens TS, Schaiff R, Prentice D, Sherman G, Shannon W, Kollef MH. Effect of a nursing-implemented sedation protocol on the duration of mechanical ventilation. Crit Care Med. 1999 Dec;27(12):2609-15.

De Jonghe B, Bastuji-Garin S, Fangio P, Lacherade JC, Jabot J, Appéré-De-Vecchi C, Rocha N, Outin H. Sedation algorithm in critically ill patients without acute brain injury. Crit Care Med. 2005 Jan;33(1):120-7.

Quenot JP, Ladoire S, Devoucoux F, Doise JM, Cailliod R, Cunin N, Aubé H, Blettery B, Charles PE. Effect of a nurse-implemented sedation protocol on the incidence of ventilator-associated pneumonia. Crit Care Med. 2007 Sep;35(9):2031-6.

Kress JP, Pohlman AS, O'Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med. 2000 May 18;342(20):1471-7.

Strøm T, Martinussen T, Toft P. A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet. 2010 Feb 6;375(9713):475-80. doi: 10.1016/S0140-6736(09)62072-9. Epub 2010 Jan 29.

Treggiari MM, Romand JA, Yanez ND, Deem SA, Goldberg J, Hudson L, Heidegger CP, Weiss NS. Randomized trial of light versus deep sedation on mental health after critical illness. Crit Care Med. 2009 Sep;37(9):2527-34. doi: 10.1097/CCM.0b013e3181a5689f.

Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE Jr, Inouye SK, Bernard GR, Dittus RS. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004 Apr 14;291(14):1753-62.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

SRLF Trial Group. Impact of oversedation prevention in ventilated critically ill patients: a randomized trial-the AWARE study. Ann Intensive Care. 2018 Sep 21;8(1):93. doi: 10.1186/s13613-018-0425-3.

• 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 ( EudraCT Number )
• First Posted: June 12, 2012
• Last Update Posted: August 26, 2015
• Last Verified: August 2015

Keywords provided by French Society for Intensive Care:

intensive care; mechanical ventilation; sedatives; morphinics; oversedation; mortality; midazolam; propofol; pain; agitation

Additional relevant MeSH terms:

Hypnotics and Sedatives; Central Nervous System Depressants; Physiological Effects of Drugs