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

This study has been completed.
Sponsor:
Information provided by:
Orion Corporation, Orion Pharma
ClinicalTrials.gov Identifier:
NCT00479661
First received: May 25, 2007
Last updated: August 12, 2010
Last verified: August 2010
  Purpose

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.


Condition Intervention Phase
Continuous Sedation in Initially Sedated Adults in ICU
Drug: Dexmedetomidine
Drug: Propofol
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Prospective, Multi-centre, Randomised, Double-blind Comparison of Intravenous Dexmedetomidine With Propofol for Continuous Sedation of Ventilated Patients in Intensive Care Unit

Resource links provided by NLM:


Further study details as provided by Orion Corporation, Orion Pharma:

Primary Outcome Measures:
  • 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. [ Time Frame: 2 hourly and before each rescue treatment dose during the treatment period and the 48-hour follow-up ] [ Designated as safety issue: No ]
  • Duration of mechanical ventilation [ Time Frame: Start and stop times of mechanical ventilation while the patient is treated in the ICU ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Nurse's assessment of subject communication with visual analogue scales (VAS) [ Time Frame: At the end of each nursing shift during study treatment and 48 h follow-up period in the ICU ] [ Designated as safety issue: No ]
  • Length of ICU stay [ Time Frame: Admission and discharge dates and times during the current ICU treatment period ] [ Designated as safety issue: No ]

Enrollment: 500
Study Start Date: May 2007
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Dexmedetomidine
Drug: Dexmedetomidine
Continuous infusion
Active Comparator: 2
Propofol
Drug: Propofol
Continuous infusion

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00479661

  Hide Study Locations
Locations
Belgium
Onze-Lieve-Vrouw Ziekenhuis, Anesthesia and Intensive Care Dept. Moorselbaan 164
Aalst, Belgium, 9300
Ziekenhuis Oost-Limburg Location Sint-Jan, Dept.of Anesthesiology, Schiepse Bos
Genk, Belgium, 3600
Finland
HUCH, Jorvi Hospital, Turuntie 150,
Espoo, Finland, 02740
HUCH, Meilahti Hospital, Haartmaninkatu 4, P.O.Box 340,
Helsinki, Finland, 00029
North Carelia Central Hospital, Tikkamaentie 16,
Joensuu, Finland, 80210
Kuopio University Hospital
Kuopio, Finland, 70210
Paijat-Hame Central Hospital, Keskussairaalankatu 7,
Lahti, Finland, 15850
South Carelia Central Hospital, Valto Kakelan katu 1,
Lappeenranta, Finland, 53130
Seinajoki Central Hospital, Hanneksenrinne 7,
Seinajoki, Finland, 60220
Tampere University Hospital, ICU, Teiskonntie 35, P.O.Box 2000,
Tampere, Finland, 33521
Germany
Charite Berlin Klinik fur Anasthesiologie und Operative Intensivmedizin (CCM), Luisenstrasse 65 (LU 65),
Berlin, Germany, 10117
Universitatsklinikum Bonn, Klinik u. Poliklinik f. Anasthesiologie u.
Bonn, Germany, 53105
Universitatsklinikum, Krankenhausstrsse 12,
Erlangen, Germany, 91054
Klinikum der Johann-Wolfgang-Goethe Universitat, Klinik fur Anasthesiologie,
Frankfurt am Main, Germany, 60590
Univ. Giessen und Marburg Abt. Anaesthesiologie, Intensivmedizin, Schmerztherapie & Palliativmedizin, Rudolf-Buchheim-Strasse 7,
Giessen, Germany, 35392
Universitatsklinikum Halle, Universitatsklinik fur Anasthelsiologie und Operative Intensivmedizin, Ernst-Grube Strasse 40
Halle, Germany, 06097
Universitatsklinikum Heidelberg Klinik fur Anasthesiologie, Im Neuenheimer Feld 110,
Heidelberg, Germany, 69120
Klinik fur Anasthesiologie, Intensivmedizin und Schmerztherapie, Universitatsklinikum des Saarlandes, Gebaude 57,
Homburg, Germany, 66421
Klinikum St. Georg, Delitzscher Strasse 141, Hause 20, 1. Etage, Zimmer 204
Leipzig, Germany, 04129
Universitatsklinikum Leipzig, Klinik und Poliklinik fur Anaesthesiologie und Intensivtherapie, Liebigstrasse 29
Leipzig, Germany, 04103
Universitatsklinikum Tubingen, Klinik fur Anasthesiologie und Intensivmedizin
Tubingen, Germany, 72076
Klinikum-Wetzlar-Braunfels, Forsthaus Strasse 1-3a
Wetzlar, Germany, 35578
Netherlands
Jeroen Bosch Ziekenhuis, Postbus 90153,
Hertogenbosch, Netherlands, 5200 ME
Westfries Gasthuis, Department Intensieve Zorgen, Maelsonstraat 3,
Hoorn, Netherlands, 1624 NP
Rivierenland Hospital, Pres. Kennedylaan 1,
Tiel, Netherlands, 4001 WP
Russian Federation
Kemerovo Stte Medical Academy, 22/A Voroshilov Street
Kemerovo, Russian Federation, 650026
Municipal Hospital #2, Krasnodar Diversified Treatment and Diagnostic Association, 6, Ulica Krasnykh Partizan Building 2,
Krasnodar, Russian Federation, 350012
Federal State Institution Russian Centre of Functional Surgical Gastroenterology, Krasnodor Municipal Hospital, 4, ulica Sedina,
Krasnodar, Russian Federation, 350086
State Institution B.B. Petrovsky Russian Research Centre of Surgery of RAMS, 2, Abrikosovsky per.
Moscow, Russian Federation, 119992
State Healthcare Institution V.A. Baranov Republican Hospital, 3, Pirogova Ulica,
Petrozavodsk, Russian Federation, 185019
Federal State Healthcare Institution L.G. Sokolov Clinical Hospital, #122 of FMBA of Russia, 4, pr-t Kultury
St .Petersburg, Russian Federation, 194291
Medical Academy of Postgraduate Study, 41, ulica Kirochnaya,
St. Petersburg, Russian Federation, 191015
Switzerland
Inselspital, Freiburgstsrasse 4,
Bern, Switzerland, CH-3010
United Kingdom
West Suffolk Hospital NHS Trust, Hardwick Lane, Suffolk,
Bury Saint Edmunds, United Kingdom, IP33 2QZ
Edinburgh University, Little France Crescent, Edinburgh Royal Infirmary,
Edinburgh, United Kingdom, EH16 2SA
Leeds General Infirmary, Great George Street
Leeds, United Kingdom, LS1 3EX
Saint John's Hospital, Howden Road West,
Livingston, United Kingdom, EH54 6PP
Saint Thomas Hospital, Lambeth Palace Road,
London, United Kingdom, SE1 7EH
Saint George's Hospital, Blackshaw Road, Tooting
London, United Kingdom, SW17 0QT
Freeman Hospital, Freeman Road High Heaton,Newcastle Upon Tyne
Tyne and Wear, United Kingdom, NE7 7DN
Sponsors and Collaborators
Orion Corporation, Orion Pharma
Investigators
Principal Investigator: Esko Ruokonen, MD Kuopio University Hospital
Study Director: Kati Kaijasilta, MSc (Pharm) Orion Corporation, Orion Pharma
  More Information

No publications provided by Orion Corporation, Orion Pharma

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Kati Kaijasilta, Orion corporation, Orion Pharma, Clinical R&D
ClinicalTrials.gov Identifier: NCT00479661     History of Changes
Other Study ID Numbers: 3005012, EudraCT 2006-006030-17
Study First Received: May 25, 2007
Last Updated: August 12, 2010
Health Authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP
Finland: Finnish Medicines Agency
Germany: Federal Institute for Drugs and Medical Devices
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Switzerland: Swissmedic

Keywords provided by Orion Corporation, Orion Pharma:
initial sedation
mechanical ventilation

Additional relevant MeSH terms:
Propofol
Dexmedetomidine
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014