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

Tracking Information
First Submitted Date ICMJE	May 31, 2007
First Posted Date ICMJE	June 1, 2007
Last Update Posted Date	May 7, 2012
Study Start Date ICMJE	June 2007
Actual Primary Completion Date	August 2009 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: May 31, 2007)	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: 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 [ Time Frame: This variable will be dependent on the individual patient and the number of days they require mechanical ventilation . ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT00481312 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: May 31, 2007)	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. [ Time Frame: 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 [ Time Frame: Number of days a patient is in ICU which will vary depending on the underlying illness of the patient ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Dexmedetomidine Versus Midazolam for Continuous Sedation in the Intensive Care Unit (ICU)
Official Title ICMJE	A Prospective, Multi-centre, Randomised, Double-blind Comparison of Intravenous Dexmedetomidine With Midazolam for Continuous Sedation of Ventilated Patients in Intensive Care Unit
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 Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Condition ICMJE	Continuous Sedation in Initially Sedated Adults in ICU
Intervention ICMJE	Drug: Dexmedetomidine Continuous Infusion; Drug: Midazolam Continuous Infusion
Study Arms	Active Comparator: 1 Dexmedetomidine Intervention: Drug: Dexmedetomidine; Active Comparator: 2 Midazolam Intervention: Drug: Midazolam
Publications *	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;19:67. doi: 10.1186/s13054-015-0787-y.; 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.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: November 23, 2009)	501
Original Estimated Enrollment ICMJE; (submitted: May 31, 2007)	500
Actual Study Completion Date	October 2009
Actual Primary Completion Date	August 2009 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Belgium, Estonia, Finland, France, Germany, Netherlands, Norway, Switzerland, United Kingdom
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00481312
Other Study ID Numbers ICMJE	3005013
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Orion Corporation, Orion Pharma
Study Sponsor ICMJE	Orion Corporation, Orion Pharma
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Stephan Jakob, MD PhD Insel Spital, Bern CH-3010 Switzerland Study Director: Angela Ruck, BSc PhD Orion Pharma R&D Nottingham England
PRS Account	Orion Corporation, Orion Pharma
Verification Date	November 2009
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP