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

NCT00479661 | Completed Phase 3 DMC

• 2 other identifiers: 3005012EudraCT 2006-006030-17
• Study Type: interventional
• Target: 500
• Locations: 7 countries
• Sites: 40

Brief Summary

Patients in the 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. Propofol 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 propofol. 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 propofol. In this study, we hope to show that: dexmedetomidine is at least as good as propofol in helping patients to sleep better and making them more comfortable, and that they are able to communicate and cooperate better with the staff treating them, and that patients treated with dexmedetomidine require a shorter time on the ventilator than those treated with propofol.

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.

  2 hourly and before each rescue treatment dose during the treatment period and the 48-hour follow-up

• Duration of mechanical ventilation

  Start and stop times of mechanical ventilation while the patient is treated in the ICU

Secondary Outcomes (2)

• Nurse's assessment of subject communication with visual analogue scales (VAS)

  At the end of each nursing shift during study treatment and 48 h follow-up period in the ICU

• Length of ICU stay

  Admission and discharge dates and times during the current ICU treatment period

Study Arms (2)

1

EXPERIMENTAL

Dexmedetomidine

Drug: Dexmedetomidine

2

ACTIVE COMPARATOR

Propofol

Drug: Propofol

Interventions

Dexmedetomidine DRUG

Continuous infusion

1

Propofol 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 more than 18 years
• 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 propofol
• 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 more than 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 mean arterial pressure \[MAP\] \< 55 mmHg despite volume and pressors)
• Severe bradycardia (heart rate \[HR\] \< 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
• 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 who are 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
• Positive pregnancy test or currently lactating

Sponsors & Collaborators

• Orion Corporation, Orion Pharma: lead

Study Sites (40)

Onze-Lieve-Vrouw Ziekenhuis, Anesthesia and Intensive Care Dept. Moorselbaan 164

Aalst, 9300, Belgium

Location

Ziekenhuis Oost-Limburg Location Sint-Jan, Dept.of Anesthesiology, Schiepse Bos

Genk, 3600, Belgium

Location

HUCH, Jorvi Hospital, Turuntie 150,

Espoo, 02740, Finland

Location

HUCH, Meilahti Hospital, Haartmaninkatu 4, P.O.Box 340,

Helsinki, 00029, Finland

Location

North Carelia Central Hospital, Tikkamaentie 16,

Joensuu, 80210, Finland

Location

Kuopio University Hospital

Kuopio, 70210, Finland

Location

Paijat-Hame Central Hospital, Keskussairaalankatu 7,

Lahti, 15850, Finland

Location

South Carelia Central Hospital, Valto Kakelan katu 1,

Lappeenranta, 53130, Finland

Location

Seinajoki Central Hospital, Hanneksenrinne 7,

Seinäjoki, 60220, Finland

Location

Tampere University Hospital, ICU, Teiskonntie 35, P.O.Box 2000,

Tampere, 33521, Finland

Location

Charite Berlin Klinik fur Anasthesiologie und Operative Intensivmedizin (CCM), Luisenstrasse 65 (LU 65),

Berlin, 10117, Germany

Location

Universitatsklinikum Bonn, Klinik u. Poliklinik f. Anasthesiologie u.

Bonn, 53105, Germany

Location

Universitatsklinikum, Krankenhausstrsse 12,

Erlangen, 91054, Germany

Location

Klinikum der Johann-Wolfgang-Goethe Universitat, Klinik fur Anasthesiologie,

Frankfurt am Main, 60590, Germany

Location

Univ. Giessen und Marburg Abt. Anaesthesiologie, Intensivmedizin, Schmerztherapie & Palliativmedizin, Rudolf-Buchheim-Strasse 7,

Giessen, 35392, Germany

Location

Universitatsklinikum Halle, Universitatsklinik fur Anasthelsiologie und Operative Intensivmedizin, Ernst-Grube Strasse 40

Halle, 06097, Germany

Location

Universitatsklinikum Heidelberg Klinik fur Anasthesiologie, Im Neuenheimer Feld 110,

Heidelberg, 69120, Germany

Location

Klinik fur Anasthesiologie, Intensivmedizin und Schmerztherapie, Universitatsklinikum des Saarlandes, Gebaude 57,

Homburg, 66421, Germany

Location

Universitatsklinikum Leipzig, Klinik und Poliklinik fur Anaesthesiologie und Intensivtherapie, Liebigstrasse 29

Leipzig, 04103, Germany

Location

Klinikum St. Georg, Delitzscher Strasse 141, Hause 20, 1. Etage, Zimmer 204

Leipzig, 04129, Germany

Location

Universitatsklinikum Tubingen, Klinik fur Anasthesiologie und Intensivmedizin

Tübingen, 72076, Germany

Location

Klinikum-Wetzlar-Braunfels, Forsthaus Strasse 1-3a

Wetzlar, 35578, Germany

Location

Jeroen Bosch Ziekenhuis, Postbus 90153,

's-Hertogenbosch, 5200 ME, Netherlands

Location

Westfries Gasthuis, Department Intensieve Zorgen, Maelsonstraat 3,

Hoorn, 1624 NP, Netherlands

Location

Rivierenland Hospital, Pres. Kennedylaan 1,

Tiel, 4001 WP, Netherlands

Location

Kemerovo Stte Medical Academy, 22/A Voroshilov Street

Kemerovo, 650026, Russia

Location

Municipal Hospital #2, Krasnodar Diversified Treatment and Diagnostic Association, 6, Ulica Krasnykh Partizan Building 2,

Krasnodar, 350012, Russia

Location

Federal State Institution Russian Centre of Functional Surgical Gastroenterology, Krasnodor Municipal Hospital, 4, ulica Sedina,

Krasnodar, 350086, Russia

Location

State Institution B.B. Petrovsky Russian Research Centre of Surgery of RAMS, 2, Abrikosovsky per.

Moscow, 119992, Russia

Location

State Healthcare Institution V.A. Baranov Republican Hospital, 3, Pirogova Ulica,

Petrozavodsk, 185019, Russia

Location

Medical Academy of Postgraduate Study, 41, ulica Kirochnaya,

Saint Petersburg, 191015, Russia

Location

Federal State Healthcare Institution L.G. Sokolov Clinical Hospital, #122 of FMBA of Russia, 4, pr-t Kultury

Saint Petersburg, 194291, Russia

Location

Inselspital, Freiburgstsrasse 4,

Bern, CH-3010, Switzerland

Location

West Suffolk Hospital NHS Trust, Hardwick Lane, Suffolk,

Bury St Edmunds, IP33 2QZ, United Kingdom

Location

Edinburgh University, Little France Crescent, Edinburgh Royal Infirmary,

Edinburgh, EH16 2SA, United Kingdom

Location

Leeds General Infirmary, Great George Street

Leeds, LS1 3EX, United Kingdom

Location

Saint John's Hospital, Howden Road West,

Livingston, EH54 6PP, United Kingdom

Location

Saint Thomas Hospital, Lambeth Palace Road,

London, SE1 7EH, United Kingdom

Location

Saint George's Hospital, Blackshaw Road, Tooting

London, SW17 0QT, United Kingdom

Location

Freeman Hospital, Freeman Road High Heaton,Newcastle Upon Tyne

Tyne and Wear, NE7 7DN, 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; Propofol

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Esko Ruokonen, MD

  Kuopio University Hospital

  PRINCIPAL INVESTIGATOR

• Kati Kaijasilta, MSc (Pharm)

  Orion Corporation, Orion Pharma

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: May 25, 2007
• First Posted: May 28, 2007
• Study Start: May 1, 2007
• Primary Completion: March 1, 2010
• Study Completion: March 1, 2010
• Last Updated: August 13, 2010

Record last verified: 2010-08

Locations

FI (8); RU (7); CH (1); GB (7); DE (12); NL (3); BE (2)