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

Phase 3

Completed

• Conditions: Continuous Sedation in Initially Sedated Adults in ICU
• Interventions: Drug: Dexmedetomidine; Drug: Midazolam

• Registration Number: NCT00481312
• Lead Sponsor: Orion Corporation, Orion Pharma

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.

Study Timeline

• Study First Submitted: 2007-05-31
• Study First Submitted QC: 2007-05-31
• Study Start: 2007-06
• Study First Posted: 2007-06-01
• Primary Completion: 2009-08
• Study Completion: 2009-10
• Status Verified: 2009-11
• Last Update Submitted: 2012-05-04
• Last Update Posted: 2012-05-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 501

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Dexmedetomidine	Dexmedetomidine
2	Midazolam	Midazolam

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (43)

ULB Erasme, Route de Lennik; 🇧🇪 Brussels, Belgium

UZ Brussel, Intensive Care Dept. Laarbeeklaan 101; 🇧🇪 Brussels, Belgium

Universitaer Ziekenhuis Gent, Intensieve Zorgen, De Pintelaan 185; 🇧🇪 Gent, Belgium

CHU de Liege (Sart Tilman), Domaine de Sart-Tilman; 🇧🇪 Liege, Belgium

East Tallinn Central Hospital, Ravi Stret 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

Oulu University Hospital, Kajaanintie 50; 🇫🇮 Oulu, Finland

Tampere University Hospital, ICU; 🇫🇮 Tampere, Finland

Centre Hospitalier Universitaire d'Angers, Reanimation medicale est de Mededicne Hyperbare, 4 Rue Larrey; 🇫🇷 Angers cedex 9, 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 cedex 09, France

Centre Hospitalier La Roche sur Yon CHD les Oudaireis, Service Reanimation CHD la Roche sur Yon, Les Oudairies; 🇫🇷 La Roche sur Yon Cedex, 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; 🇫🇷 Orleans cedex 1, 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

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

Isala Klinieken, Locatie Weezenlanden, Groot Wezenland 20; 🇳🇱 Zwolle, Netherlands

Universitatsklinikum Tubingen, Klinik fur Anasthesiologie und Intensivmedizin, Hoppe-Seyler-Strasse 3; 🇩🇪 Tubingen, Germany

Ulleval University Hospital, Medical and Surgical ICU, Kirkeveien 166; 🇳🇴 Oslo, Norway

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

Viecuri MC voor Noord-Limburg, Locatie Venlo, Dept. Intensieve Zorgen, Tegelseweg 210; 🇳🇱 Venlo, Netherlands

Kantonsspital Winterthur, Brauerstrasse 15,; 🇨🇭 Winterthur, Switzerland

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

Kennemer Hospital, Boeerhaavelaan 29; 🇳🇱 Haarlem, Netherlands

Saint Elisabeth Ziekenhuis, Dept. Intensieve Zorgen, Hilvarenbeekseweg 60; 🇳🇱 Tilburg, Netherlands

Hopital Albert Calmette, Boulevard Du Pr. Jules Leclercq; 🇫🇷 Lille, France

North Estonian Regional Hospital, Centre of Intensive Care, J. Sutiste Tee 18; 🇪🇪 Tallinn, Estonia

Albert Schweitzer Hospital, Locatie Dordwikj, Albert Schweitzerplaats 25; 🇳🇱 Dordrecht, Netherlands

Haukeland University Hospital, Intensive Care Unit, Jonas Liesvei 65; 🇳🇴 Bergen, Norway

Rikshospitalet, Universitetsklinikk, Sognsvannsveien 20; 🇳🇴 Oslo, Norway

Aker Universtetssykehus HF, Anestesiavdelingen, Trondheimsveien 235; 🇳🇴 Oslo, Norway

Inselspital, Freiburgstrasse 4; 🇨🇭 Bern, 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