A PROSPECTIVE, MULTI-CENTRE, RANDOMISED, DOUBLE-BLIND COMPARISON OF INTRAVENOUS DEXMEDETOMIDINE WITH PROPOFOL FOR CONTINUOUS SEDATION OF VENTILATED PATIENTS IN INTENSIVE CARE UNIT - Prodex

• Register: EUCTR
• Last refreshed on: 28 January 2013
• Main ID: EUCTR2006-006030-17-DE
• Date of registration: 13/06/2007
• Prospective Registration: Yes
• Primary sponsor: Orion Corporation Orion Pharma
• Public title: A PROSPECTIVE, MULTI-CENTRE, RANDOMISED, DOUBLE-BLIND COMPARISON OF INTRAVENOUS DEXMEDETOMIDINE WITH PROPOFOL FOR CONTINUOUS SEDATION OF VENTILATED PATIENTS IN INTENSIVE CARE UNIT - Prodex
• Scientific title: A PROSPECTIVE, MULTI-CENTRE, RANDOMISED, DOUBLE-BLIND COMPARISON OF INTRAVENOUS DEXMEDETOMIDINE WITH PROPOFOL FOR CONTINUOUS SEDATION OF VENTILATED PATIENTS IN INTENSIVE CARE UNIT - Prodex
• Date of first enrolment: 16/10/2007
• Target sample size: 500
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-006030-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Finland, Germany, Netherlands, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
• Age = 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 = 72 hours from ICU admission and = 48 hours of commencing continuous sedation in the ICU
• Patients should have an expected requirement for sedation = 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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 less than 55 mmHg despite volume and pressors)
• Severe bradycardia (HR less than 50 beats/min)
• AV-conduction block II-III (unless pacemaker installed)
• Severe hepatic impairment (bilirubin more than 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 and other injuries requiring regular anaesthesia or surgery
• Use of centrally acting a2 agonists or antagonists (e.g. clonidine, titzanidine, apraclonidine and brimonidine) within 24 hours prior to randomisation
• 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-Barre 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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients requiring mechanical ventilation and sedation in ICU.
MedDRA version: 8.0 Level: LLT Classification code 10039897

Intervention(s)

Trade Name: Precedex 100 microg/ml
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Dexmedetomidine
CAS Number: 145108-58-3
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Trade Name: Propofol-Lipuro 20 mg/ml
Pharmaceutical Form: Emulsion for injection
INN or Proposed INN: propofol
Concentration unit: mg/ml milligram(s)/millilitre
Concentration number: 20-
Pharmaceutical form of the placebo: Injection*
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Secondary Objective: The secondary objectives of this study are:
• To show that dexmedetomidine improves rousability, communication of pain and cooperation compared with propofol using nurse’s assessment of subject communication
• To show that dexmedetomidine shortens length of ICU stay compared with propofol
• To evaluate the safety of dexmedetomidine compared to propofol

Main Objective: The study has hierarchical co-primary objectives to demonstrate that:
• Firstly: dexmedetomidine is at least as effective as sedation with propofol and daily sedation stops, in maintaining a target depth of sedation in ventilated patients in intensive care unit (ICU)
• Secondly: use of dexmedetomidine, compared with sedation with propofol and daily sedation stops, reduces the duration of mechanical ventilation in ventilated patients in ICU

Primary end point(s): • 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. In addition, RASS score should be assessed each time rescue treatment is given to maintain the target sedation level.
• Duration of mechanical ventilation

Secondary ID(s)

2006-006030-17-FI

3005012