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

NCT ID: NCT00481312

Last Updated: 2012-05-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 501 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-06-30
• Study Completion Date: 2009-10-31

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.

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 midazolam or switch to dexmedetomidine. Patients should not have received any other continuously or regularly administered sedative agent than midazolam infusion 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. propofol 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: DOUBLE

Study Groups

1

Dexmedetomidine

Group Type: ACTIVE_COMPARATOR

Dexmedetomidine

Intervention Type: DRUG

Continuous Infusion

2

Midazolam

Group Type: ACTIVE_COMPARATOR

Midazolam

Intervention Type: DRUG

Continuous Infusion

Interventions

Dexmedetomidine

Continuous Infusion

Intervention Type: DRUG

Midazolam

Continuous Infusion

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

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 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
• 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

Responsibility Role: SPONSOR

Principal Investigators

Stephan Jakob, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Insel Spital, Bern CH-3010 Switzerland

Angela Ruck, BSc PhD

Role: STUDY_DIRECTOR

Orion Pharma R&D Nottingham England

Locations

ULB Erasme, Route de Lennik

Brussels, , Belgium

UZ Brussel, Intensive Care Dept. Laarbeeklaan 101

Brussels, , Belgium

Universitaer Ziekenhuis Gent, Intensieve Zorgen, De Pintelaan 185

Ghent, , Belgium

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

Liège, , Belgium

East Tallinn Central Hospital, Ravi Stret 18

Tallinn, , Estonia

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

Tallinn, , Estonia

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

Tallinn, , Estonia

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

Tartu, , Estonia

Tampere University Hospital, ICU

Tampere, Pirkanmaa, Finland

Oulu University Hospital, Kajaanintie 50

Oulu, , Finland

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

Angers, , France

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

Argenteuil, , France

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

Grenoble, , France

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

La Roche-sur-Yon, , France

Hopital Albert Calmette, Boulevard Du Pr. Jules Leclercq

Lille, , France

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

Limoges, , France

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

Orléans, , France

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

Paris, , France

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

Paris, , France

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

Paris, , France

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

Poitiers, , France

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

Tours, , France

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

Bonn, , Germany

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

Greifswald, , Germany

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

Tübingen, , Germany

VU Medisch Centrum, De Boelelaan 1117

Amsterdam, , Netherlands

Gelre Hospitals - Locatie Lucas, A.Schweitzerlaan 32

Apeldoorn, , Netherlands

Amphia Ziekenhuis, Dept. Intensieve Zorgen, Molengracht 21

Breda, , Netherlands

Albert Schweitzer Hospital, Locatie Dordwikj, Albert Schweitzerplaats 25

Dordrecht, , Netherlands

Kennemer Hospital, Boeerhaavelaan 29

Haarlem, , Netherlands

Saint Elisabeth Ziekenhuis, Dept. Intensieve Zorgen, Hilvarenbeekseweg 60

Tilburg, , Netherlands

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

Venlo, , Netherlands

Isala Klinieken, Locatie Weezenlanden, Groot Wezenland 20

Zwolle, , Netherlands

Haukeland University Hospital, Intensive Care Unit, Jonas Liesvei 65

Bergen, , Norway

Rikshospitalet, Universitetsklinikk, Sognsvannsveien 20

Oslo, , Norway

Ulleval University Hospital, Medical and Surgical ICU, Kirkeveien 166

Oslo, , Norway

Aker Universtetssykehus HF, Anestesiavdelingen, Trondheimsveien 235

Oslo, , Norway

Inselspital, Freiburgstrasse 4

Bern, , Switzerland

Kantonsspital Winterthur, Brauerstrasse 15,

Winterthur, , Switzerland

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

Zurich, , Switzerland

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

Birmingham, , United Kingdom

Birmingham Heartlands Hospital, Bordesely Green East

Birmingham, , United Kingdom

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

Plymouth, , United Kingdom

Countries

Belgium; Estonia; Finland; France; Germany; Netherlands; Norway; 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

3005013

Identifier Type: -

Identifier Source: org_study_id