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

NCT ID: NCT00479661

Last Updated: 2010-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 500 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-05-31
• Study Completion Date: 2010-03-31

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.

Detailed Description

This is a phase III, multi-centre, prospective, randomised, double-blind, double-dummy, active comparator study. The study consists of three periods: screening, double-dummy treatment and follow-up period.

All patients admitted to ICU will be pre-screened according to inclusion and exclusion criteria prior to informed consent using available clinical data.

Informed consent, screening and randomisation procedures should be completed within 72 hours from the time of admission to ICU and within 48 hours from starting continuous sedation. Eligible study subjects requiring light to moderate sedation (Richmond Agitation-Sedation Scale [RASS] = 0 to -3) will be randomised to either continue on propofol or switch to dexmedetomidine. Patients should not have received any other continuously or regularly administered sedative agent than propofol during the last 12 hours except for opioid analgesics. Study treatments will be titrated to achieve an individually targeted sedation range determined on a daily basis. Rescue treatment (i.e. midazolam boli) may be given if needed to achieve the target depth of sedation. Continued need for sedation will be assessed at a daily sedation stop, conducted at the same time each day. First sedation stop may be 12-36 hours from randomisation, depending on the time of day the study subject is randomised. The duration of study treatment is limited to a maximum of 14 days from randomisation. Following withdrawal of sedation, study subjects will be monitored for 48 hours and contacted by telephone 31 and 45 days after randomisation.

Conditions

Continuous Sedation in Initially Sedated Adults in ICU

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

Dexmedetomidine

Group Type: EXPERIMENTAL

Dexmedetomidine

Intervention Type: DRUG

Continuous infusion

2

Propofol

Group Type: ACTIVE_COMPARATOR

Propofol

Intervention Type: DRUG

Continuous infusion

Interventions

Dexmedetomidine

Continuous infusion

Intervention Type: DRUG

Propofol

Continuous infusion

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• Received any investigational drug within the preceding 30 days
• Concurrent participation in any other interventional study (any study in which patients are allocated to different treatment groups and/or non-routine diagnostic or monitoring procedures are performed)
• Previous participation in this study
• Any other condition which, in the investigator's opinion, would make it detrimental for the subject to participate in the study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Orion Corporation, Orion Pharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Orion corporation, Orion Pharma, Clinical R&D

Principal Investigators

Esko Ruokonen, MD

Role: PRINCIPAL_INVESTIGATOR

Kuopio University Hospital

Kati Kaijasilta, MSc (Pharm)

Role: STUDY_DIRECTOR

Orion Corporation, Orion Pharma

Locations

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

Aalst, , Belgium

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

Genk, , Belgium

HUCH, Jorvi Hospital, Turuntie 150,

Espoo, , Finland

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

Helsinki, , Finland

North Carelia Central Hospital, Tikkamaentie 16,

Joensuu, , Finland

Kuopio University Hospital

Kuopio, , Finland

Paijat-Hame Central Hospital, Keskussairaalankatu 7,

Lahti, , Finland

South Carelia Central Hospital, Valto Kakelan katu 1,

Lappeenranta, , Finland

Seinajoki Central Hospital, Hanneksenrinne 7,

Seinäjoki, , Finland

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

Tampere, , Finland

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

Berlin, , Germany

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

Bonn, , Germany

Universitatsklinikum, Krankenhausstrsse 12,

Erlangen, , Germany

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

Frankfurt am Main, , Germany

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

Giessen, , Germany

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

Halle, , Germany

Universitatsklinikum Heidelberg Klinik fur Anasthesiologie, Im Neuenheimer Feld 110,

Heidelberg, , Germany

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

Homburg, , Germany

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

Leipzig, , Germany

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

Leipzig, , Germany

Universitatsklinikum Tubingen, Klinik fur Anasthesiologie und Intensivmedizin

Tübingen, , Germany

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

Wetzlar, , Germany

Jeroen Bosch Ziekenhuis, Postbus 90153,

's-Hertogenbosch, , Netherlands

Westfries Gasthuis, Department Intensieve Zorgen, Maelsonstraat 3,

Hoorn, , Netherlands

Rivierenland Hospital, Pres. Kennedylaan 1,

Tiel, , Netherlands

Kemerovo Stte Medical Academy, 22/A Voroshilov Street

Kemerovo, , Russia

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

Krasnodar, , Russia

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

Krasnodar, , Russia

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

Moscow, , Russia

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

Petrozavodsk, , Russia

Medical Academy of Postgraduate Study, 41, ulica Kirochnaya,

Saint Petersburg, , Russia

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

Saint Petersburg, , Russia

Inselspital, Freiburgstsrasse 4,

Bern, , Switzerland

West Suffolk Hospital NHS Trust, Hardwick Lane, Suffolk,

Bury St Edmunds, , United Kingdom

Edinburgh University, Little France Crescent, Edinburgh Royal Infirmary,

Edinburgh, , United Kingdom

Leeds General Infirmary, Great George Street

Leeds, , United Kingdom

Saint John's Hospital, Howden Road West,

Livingston, , United Kingdom

Saint Thomas Hospital, Lambeth Palace Road,

London, , United Kingdom

Saint George's Hospital, Blackshaw Road, Tooting

London, , United Kingdom

Freeman Hospital, Freeman Road High Heaton,Newcastle Upon Tyne

Tyne and Wear, , United Kingdom

Countries

Belgium; Finland; Germany; Netherlands; Russia; Switzerland; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 25887576 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22436955 (View on PubMed)

Other Identifiers

EudraCT 2006-006030-17

Identifier Type: -

Identifier Source: secondary_id

3005012

Identifier Type: -

Identifier Source: org_study_id