E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Delirium
The pharmacokinetic and dynamic properties of intravenous clonidine in critical ill mechanically treated patients |
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E.1.1.1 | Medical condition in easily understood language |
Acute confusion
FInding the optimal dosing scheme of intravenous clonidine in order to acheeve optimal sedation with minimal side effects. |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03] |
MedDRA Classification |
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 |
This study is developed for assessing the pharmacodynamic and pharmacokinetic properties of intravenous (IV) clonidine in critically ill patients on the ICU, and to estimate the optimal dosing strategy for IV clonidine
Hemodynamic parameters:
Heart rate, blood pressure, 2-hrly for the first 12 h, 8-hrly thereafter.
Laboratory parameters:
Serum creatinine daily
Albumin concentrations at study entry
Clinical parameters:
CAM-ICU delirium scale 8-hrly
RASS sedation scale 8-hrly
Need for fixation
CVVH or dialysis
Medication:
Total amounts and average daily doses of:
Noradrenalin, dobutamine, midazolam, morfine, propofol, haloperidol, other antipsychotics.
Safety parameters:
Adverse events
Serious adverse events |
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E.2.2 | Secondary objectives of the trial |
Pharmacokinetic data:
Clonidine plasma concentration at start of infusion at t=2, t=4, t=8 and t=12 h
Clonidine plasma concentration during study, once daily
Clonidine plasma concentration after stopping infusion at t=ω+8, t=ω+16, t=ω+24 h, and t=ω+48 h (ω= end of infusion). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• at least 18 years of age
• intubated
• sedated
at the start of the study. Because of the high incidence of delirium on the ICU in all age categories, all age groups > 18 years will be included.
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E.4 | Principal exclusion criteria |
• Severe neurotrauma,
• Severe dementia (living in a nursing home)
• Inability to speak Dutch or English, which is one of the causes of not being able to use the CAM-ICU.
• The use of clonidine during the 96 hours before the start of the study.
• Bradycardia (<50/min)
• Severe hypotension (MAP < 65 after volume resuscitation and vasopressors)
• Pregnancy and lactation (pregnancy test are routinely performed in premenopausal women on the ICU).
• Epilepsy
• Known clonidine intolerance
• Liver cirrhosis (Child Pugh class C)
• Recent and acute myocardial infarction
• Severe heart failure (LVEF < 30%)
• Second or third degree AV-block without a permanent pacemaker
• Expected transfer to another hospital. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Cessation of the need for sedative therapy |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
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) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
control group without investigational medicine or placebo |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |