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

Tracking Information

• First Submitted Date: June 6, 2012
• First Posted Date: June 12, 2012
• Last Update Posted Date: August 26, 2015
• Study Start Date: June 2012
• Actual Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 8, 2012): Day-90 mortality [ Time Frame: Mortality at Day 90 after randomization ]
• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT01617265 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: June 12, 2012)

• Mortality at Day 28 [ Time Frame: at day 28 ]
• Hospital mortality [ Time Frame: at hospital discharge, up to day 90 ]
• 1-yr mortality [ Time Frame: at 1 yr ]
• Mechanical ventilation duration [ Time Frame: From onset of mechanical ventilation to day 28 ]
• Days alive with no mechanical ventilation [ Time Frame: From ICU admission up to day 28 ]
• Occurence of ventilator-associated pneumonia [ Time Frame: During mechanical ventilation duration, up to day 28 ]
• Use of non-invasive ventilation after extubation [ Time Frame: From extubation to ICU discharge up to day 28 ]
• Duration of ICU stay [ Time Frame: From ICU admission to ICU discharge or death in ICU, up to day 90 ]
• 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
• 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
• 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
• Time to weaning onset [ Time Frame: Time from mechancial ventilation initiation to first spontaneous breathing trial, up to day 28 ]
• Number of patients requiring tracheotomy [ Time Frame: During ICU stay, up to day 28 ]
• First sitting in chair [ Time Frame: During ICU stay, up to day 28 ]

Original Secondary Outcome Measures (submitted: June 8, 2012)

• Mortality at Day 28 [ Time Frame: at day 28 ]
• Hospital mortality [ Time Frame: at hospital discharge, up to day 90 ]
• 1-yr mortality [ Time Frame: at 1 yr ]
• MV duration [ Time Frame: From onset of mechanical ventilation to day 28 ]
• Days alive with no mechanical ventilation [ Time Frame: From ICU admission up to day 28 ]
• Occurence of ventilator-associated pneumonia [ Time Frame: During mechanical ventilation duration, up to day 28 ]
• Use of non-invasive ventilation after extubation [ Time Frame: From extubation to ICU discharge up to day 28 ]
• Duration of ICU stay [ Time Frame: From ICU admission to ICU discharge or death in ICU, up to day 90 ]
• 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
• 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
• Functional, cognitive and psychological status [ Time Frame: At day 90 and 1 year ]
  Functional status (measured on the Barthel scale), depression (measured on the HADS), PTSD (measured on the IES), QOL (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 ]
• Number of patients requiring tracheotomy [ Time Frame: During ICU stay, up to day 28 ]
• First sitting in chair [ Time Frame: During ICU stay, up to day 28 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of a Strategy to Prevent Oversedation in Intensive Care Patients Under Mechanical Ventilation
• Official Title: Prevention of Oversedation in Intensive Care Patients Under Mechanical Ventilation : the AWARE Multicentric Randomized Trial
• 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.

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 Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: ICU Patients Requiring Invasive Mechanical Ventilation

Intervention

• 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.
• Procedure: Usual sedation practice
  Sedation and analgesia will be administered according to the usual practices in each participating center.

Study Arms

• 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.
  Intervention: Procedure: Clinical Procedure to Prevent Oversedation
• Active Comparator: Conventional sedation group
  In this arm, sedation will be administered according to the usual practices in each participating center.
  Intervention: Procedure: Usual sedation practice

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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 25, 2015): 1180
• Original Estimated Enrollment (submitted: June 8, 2012): 2720
• Actual Study Completion Date: June 2015
• Actual Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT01617265
• Other Study ID Numbers: SRLF-TG-1-AWARE; 2011-004246-18 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: French Society for Intensive Care
• Study Sponsor: French Society for Intensive Care
• Collaborators: University Hospital, Tours

Investigators

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

• PRS Account: French Society for Intensive Care
• Verification Date: August 2015