E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients requiring mechanical ventilation and sedation in ICU. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10039897 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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
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E.2.2 | Secondary objectives of the trial |
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
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
3005012 Addendum 1 pharmacogenetic substudy protocol 8 November 2007 Version 2.0 Objective: to examine whether individual genetic variations relating to drug metabolism and the drug target pathway correlate with different efficacy and safety profiles of dexmedetomidine. |
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E.3 | Principal 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
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E.4 | Principal 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 α2 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
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy variables: • 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 the study treatment is titrated or rescue treatment is given to maintain the target sedation level. • Duration of mechanical ventilation
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |