Pharmacokinetics and Clinical Effects of Escalating Doses of Clonidine in ICU Patients
Information source: Deventer Ziekenhuis
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Delirium; Critical Illness
Intervention: Clonidine (Catapresan®) 0,150 mg/ml, ampoule 1 ml (Drug)
Phase: Phase 3
Status: Not yet recruiting
Sponsored by: Deventer Ziekenhuis Official(s) and/or principal investigator(s): Huub Oever v/d, Principal Investigator, Affiliation: Deventer Ziekenhuis
Overall contact: Marieke Zeeman, Phone: +31 570 535353, Email: m.zeeman@dz.nl
Summary
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.
Clinical Details
Official title: Pharmacokinetics and Clinical Effects of Escalating Doses of Clonidine in ICU Patients
Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: clonidine plasma concentrations
Secondary outcome: heart rateblood pressure delirium use of antipsychotics
Detailed description:
Many patients in intensive care units (ICU's) require sedation and analgesia to tolerate
mechanical ventilation and other ICU procedures. Commonly used GABA-ergic anaesthetics like
propofol, midazolam and morphine have potential adverse effects that may increase morbidity,
prolong ICU stay and provoke delirium. Recent studies have shown that sedation with
alpha-2-adrenergic agonists may lead to a reduction of the total amount of
gamma-aminobutyric acid (GABA) - ergic anaesthetics and reduction of delirium1In clinical
practice the alpha-2-adrenergic agent clonidine is widely used off label as an add-on
sedative in mechanically ventilated patients who suffer from delirium, but there are no
large studies proving that this therapy is effective and safe. Limited information exists on
the pharmacokinetics of iv clonidine, especially in ICU patients. Besides, dosing regimens
of clonidine differ widely among ICU's in the Netherlands, and in the literature.
The sample size required for pharmacokinetic modelling with an acceptable level of precision
is inversely related to the number of blood samplings taken from each individual. Population
pharmacokinetic experiments that have been published have generally used 50 or more
subjects. However, in the investigators study a relatively large number of blood samples are
taken (>10 per subject when the protocol is completed, see section 6. 3). THe investigators
estimate that sufficient precision can be obtained with a sample size of 24 subjects,
generating an estimated 240 to 360 blood samples.
In a recent publication of a computer simulated population pharmacokinetics of an absorption
model using a design that involved 6 samplings per subject, it was estimated that a
two-compartment first-order model would need 50 subjects (i. e. 300 blood samplings) to
obtain a model with 50% precision and a power of 0. 8.
The investigators 24 subjects will be treated with 3 different doses of clonidine (600, 1200
and 1800 µg/day), that is 8 per treatment arm.
On top of this, 8 patients receiving no clonidine will serve as a reference group, in order
to interpret hemodynamic and safety data, and to illustrate dose-response relationships.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
In order to be eligible to participate in this study, a subject must be:
- 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
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 atrioventricular (AV)-block without a permanent pacemaker
- Expected transfer to another hospital.
Locations and Contacts
Marieke Zeeman, Phone: +31 570 535353, Email: m.zeeman@dz.nl Additional Information
Starting date: November 2015
Last updated: June 9, 2015
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