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

• 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 ] [ Designated as safety issue: Yes ]
  
• 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 . ] [ Designated as safety issue: No ]
  

• 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) ] [ Designated as safety issue: Yes ]
  
• 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 ] [ Designated as safety issue: No ]
  

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.