Dexmedetomidine Versus Midazolam for Continuous Sedation in the Intensive Care Unit (ICU)

NCT00481312 | Completed Phase 3 DMC

• 1 other identifier: 3005013
• Study Type: interventional
• Target: 501
• Locations: 9 countries
• Sites: 43

Brief Summary

Patients in ICU who need help with their breathing are put onto a machine called a ventilator and are also given a medicine, called a sedative, which helps them to sleep and makes them more comfortable. Midazolam is a sedative that is routinely used for these purposes. For most patients the aim of sedation is to make them sleepy but still able to respond to nursing staff (light sedation) Dexmedetomidine is a new sedative for use in intensive care and in this clinical study, dexmedetomidine is compared to midazolam. It is thought that dexmedetomidine might be slightly better at allowing patients to be sleepy but still respond to people around them. It also does not appear to affect patient's breathing. the purpose of this study is to test whether dexmedetomidine really does have these advantages compared to midazolam. in this study we hope to show that: dexmedetomidine is at least as good as midazolam in helping patients to sleep better and making them more comfortable, and that they are able to co-operate better with the staff treating them, and that patients treated with dexmedetomidine require a shorter time on the ventilator than those treated with midazolam.

Conditions

Continuous Sedation in Initially Sedated Adults in ICU

Keywords

Initial Sedation; Mechanical ventilation

Outcome Measures

Primary Outcomes (2)

• Depth of sedation using the RASS. The target RASS range (target depth of sedation) should be 0 to -3 for a patient to be included in the study. The target may be amended during the study treatment, if clinically required

  RASS score will be assessed approximately 2 hourly during the treatment period and during the 48-hour follow-up period

• Duration of mechanical ventilation the number of days the patient receives mechanical ventilation will be recorded

  This variable will be dependent on the individual patient and the number of days they require mechanical ventilation .

Secondary Outcomes (2)

• Nurse's assessment of subject communication with visual analogue scales (VAS)Patients rousability and ability to co-operate and communicate will be measured using a visual analogue scale.

  This will be measured at the end of every nursing shift whilst the patient remains on study treatment (maximum 14 days)

• Length of ICU stay

  Number of days a patient is in ICU which will vary depending on the underlying illness of the patient

Study Arms (2)

1

ACTIVE COMPARATOR

Dexmedetomidine

Drug: Dexmedetomidine

2

ACTIVE COMPARATOR

Midazolam

Drug: Midazolam

Interventions

Dexmedetomidine DRUG

Continuous Infusion

1

Midazolam DRUG

Continuous Infusion

2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years and over
• Clinical need for sedation of an initially intubated (or tracheotomised) and ventilated (with inspiratory assistance) patient
• Prescribed light to moderate sedation (target RASS = 0 to -3) using midazolam infusion
• Patients should be randomised within 72 hours from ICU admission and within 48 hours of commencing continuous sedation in the ICU
• Patients should have an expected requirement for sedation of at least 24 hours from time of randomisation
• Written informed consent must be obtained according to local regulations before starting any study procedures other than pre-screening.

You may not qualify if:

• Acute severe intracranial or spinal neurological disorder due to vascular causes, infection, intracranial expansion or injury
• Uncompensated acute circulatory failure at time of randomisation (severe hypotension with MAP \< 55 mmHg despite volume and pressors)
• Severe bradycardia (HR \< 50 beats/min)
• AV-conduction block II-III (unless pacemaker installed)
• Severe hepatic impairment (bilirubin \> 101 µmol/L)
• Need for muscle relaxation at the time of randomisation (may only be used for intubation and initial stabilization)
• Loss of hearing or vision, or any other condition which would significantly interfere with the collection of study data
• Burn injuries requiring regular anaesthesia or surgery
• Use of centrally acting α2 agonists or antagonists at the time of randomisation, notably clonidine (see section 5.7 for prior and concomitant treatments)
• Known allergy to any of the study drugs or any excipients of the study drugs
• Patients who have or are expected to have treatment withdrawn or withheld due to poor prognosis
• Patients receiving sedation for therapeutic indications rather than to tolerate the ventilator (e.g. epilepsy)
• Patients unlikely to require continuous sedation during mechanical ventilation (e.g. Guillain-Barré syndrome)
• Patients who are unlikely to be weaned from mechanical ventilation; e.g. diseases/injuries primarily affecting the neuromuscular function of the respiratory apparatus such as clearly irreversible disease requiring prolonged ventilatory support (e.g. high spinal cord injury or advanced amyotrophic lateral sclerosis)
• Distal paraplegia

Sponsors & Collaborators

• Orion Corporation, Orion Pharma: lead

Study Sites (43)

ULB Erasme, Route de Lennik

Brussels, 1070, Belgium

Location

UZ Brussel, Intensive Care Dept. Laarbeeklaan 101

Brussels, 1090, Belgium

Location

Universitaer Ziekenhuis Gent, Intensieve Zorgen, De Pintelaan 185

Ghent, 9000, Belgium

Location

CHU de Liege (Sart Tilman), Domaine de Sart-Tilman

Liège, 3000, Belgium

Location

East Tallinn Central Hospital, Ravi Stret 18

Tallinn, 10138, Estonia

Location

North Estonian Regional Hospital, Centre of Intensive Care, J. Sutiste Tee 18

Tallinn, 13419, Estonia

Location

North Estonian Regional Hospital, Dept. of Postoperative Intensive Care, J. Sutiste Tee 18

Tallinn, 13419, Estonia

Location

Tartu University Hospistal, Clinic of Anesthesiology and Intensive Care, L. Puusepa 8

Tartu, 51014, Estonia

Location

Tampere University Hospital, ICU

Tampere, Pirkanmaa, 33521, Finland

Location

Oulu University Hospital, Kajaanintie 50

Oulu, 90029 OYS, Finland

Location

Centre Hospitalier Universitaire d'Angers, Reanimation medicale est de Mededicne Hyperbare, 4 Rue Larrey

Angers, 49933, France

Location

Centre Hospitalier Victor Dupouy Hopital Dupuytren, Service Reanimation Polyvalente, 69, Rue du Lt Colonel Prud'hon

Argenteuil, 95107, France

Location

Centre Hospitalier Universitaire de Grenoble, Service de Reanimation Medicale, Boulevard de la Chantourne, BP 217

Grenoble, 38043, France

Location

Centre Hospitalier La Roche sur Yon CHD les Oudaireis, Service Reanimation CHD la Roche sur Yon, Les Oudairies

La Roche-sur-Yon, 85925, France

Location

Hopital Albert Calmette, Boulevard Du Pr. Jules Leclercq

Lille, 59037, France

Location

Centre Hospitalier Universitaire Limoges Hopital Dupuytren, Service de Reanimation Polyvalente, 2, Avenue Martin Luther King

Limoges, 87042, France

Location

Centre Hospitalier Universitaire d'Orleans, Reanimation Medicale, 1, rue Prote Madeleine, BP 2439

Orléans, 45032, France

Location

Hopital Bichat-Claude, Dept. D'Anasehesie et Reanimation Chirurgicale, 46, rue Henri-Huchard

Paris, 75018, France

Location

Groupe Hospitalier Cochin Saint Vincent de Paul, Service de Reanimation Medicale, 27 Rue du Faubourg Saint Jacques

Paris, 75679, France

Location

Hopital Foch, Service Renimation, 40 Rue Worth, Suresnes Hauts de Seine

Paris, 92150, France

Location

Centre Hospitalier Universitaire de Poitiers, Reanimation Medicale, 2, Rue de la Miletrie

Poitiers, 86021, France

Location

Centre Hospitalier Regional et Universitaire - Hopital Bretonneau Service Reanimation Medicale Polyvalente, 2, Boulevard Tonnelle, Tours cedex 9

Tours, 37044, France

Location

Universitatsklinikum Bonn, Klinik u. Poliklinik f. Anasthesiologie u. Operative Intensivmedizin, Sigmund-Freud-Strasse 25

Bonn, 53105, Germany

Location

Universitatsklinikum Greifswald, Klinik u. Poliklinik f. Anasthesiologie u. Intensivmedizin, Friedrich-Loeffler-Str. 23b

Greifswald, 17475, Germany

Location

Universitatsklinikum Tubingen, Klinik fur Anasthesiologie und Intensivmedizin, Hoppe-Seyler-Strasse 3

Tübingen, 72076, Germany

Location

VU Medisch Centrum, De Boelelaan 1117

Amsterdam, 1081 HV, Netherlands

Location

Gelre Hospitals - Locatie Lucas, A.Schweitzerlaan 32

Apeldoorn, 7334 DZ, Netherlands

Location

Amphia Ziekenhuis, Dept. Intensieve Zorgen, Molengracht 21

Breda, 4818, Netherlands

Location

Albert Schweitzer Hospital, Locatie Dordwikj, Albert Schweitzerplaats 25

Dordrecht, 3318 AT, Netherlands

Location

Kennemer Hospital, Boeerhaavelaan 29

Haarlem, 2035 RC, Netherlands

Location

Saint Elisabeth Ziekenhuis, Dept. Intensieve Zorgen, Hilvarenbeekseweg 60

Tilburg, 5022 GC, Netherlands

Location

Viecuri MC voor Noord-Limburg, Locatie Venlo, Dept. Intensieve Zorgen, Tegelseweg 210

Venlo, 5912 BL, Netherlands

Location

Isala Klinieken, Locatie Weezenlanden, Groot Wezenland 20

Zwolle, 8011 JW, Netherlands

Location

Haukeland University Hospital, Intensive Care Unit, Jonas Liesvei 65

Bergen, 5021, Norway

Location

Rikshospitalet, Universitetsklinikk, Sognsvannsveien 20

Oslo, 0027, Norway

Location

Ulleval University Hospital, Medical and Surgical ICU, Kirkeveien 166

Oslo, 0450, Norway

Location

Aker Universtetssykehus HF, Anestesiavdelingen, Trondheimsveien 235

Oslo, 0514, Norway

Location

Inselspital, Freiburgstrasse 4

Bern, CH-3010, Switzerland

Location

Kantonsspital Winterthur, Brauerstrasse 15,

Winterthur, 8401, Switzerland

Location

Universitatsspital Zurich, Klinik fur Innere Medizin, Intensivstation, Ramistrasse 100

Zurich, 8091, Switzerland

Location

University Hospital Birmingham, Department of Anaesthesia, Queen Elizabeth Hospital,

Birmingham, B15 2TH, United Kingdom

Location

Birmingham Heartlands Hospital, Bordesely Green East

Birmingham, B9 5SS, United Kingdom

Location

Derriford Hospital, Dept. of Intensive Care Level 4, Derriford Road

Plymouth, PL6 8DH, United Kingdom

Location

Related Publications (2)

• Turunen H, Jakob SM, Ruokonen E, Kaukonen KM, Sarapohja T, Apajasalo M, Takala J. Dexmedetomidine versus standard care sedation with propofol or midazolam in intensive care: an economic evaluation. Crit Care. 2015 Feb 19;19(1):67. doi: 10.1186/s13054-015-0787-y.

  PMID: 25887576 DERIVED

• Jakob SM, Ruokonen E, Grounds RM, Sarapohja T, Garratt C, Pocock SJ, Bratty JR, Takala J; Dexmedetomidine for Long-Term Sedation Investigators. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA. 2012 Mar 21;307(11):1151-60. doi: 10.1001/jama.2012.304.

  PMID: 22436955 DERIVED

MeSH Terms

Interventions

Dexmedetomidine; Midazolam

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Stephan Jakob, MD PhD

  Insel Spital, Bern CH-3010 Switzerland

  PRINCIPAL INVESTIGATOR

• Angela Ruck, BSc PhD

  Orion Pharma R&D Nottingham England

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2007
• First Posted: June 1, 2007
• Study Start: June 1, 2007
• Primary Completion: August 1, 2009
• Study Completion: October 1, 2009
• Last Updated: May 7, 2012

Record last verified: 2009-11

Locations

CH (3); NO (4); DE (3); FI (2); NL (8); BE (4); GB (3); FR (12); ES (4)