Primary objective:Plasma levels of clonidine, in order to describe pharmacokinetic and pharmacodynamic properties of intravenous clonidine in critically ill ventilated ICU patients.Secondary objectives are: * to evaluate the effect of a 3-hr loading…
ID
Source
Brief title
Condition
- Deliria (incl confusion)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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=*+8, t=*+16, t=*
+24 h, and t=*+48 h (*= end of infusion).
clonidine concentrations in CVVH fluids
Secondary outcome
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
12hrly urine creatinin clearance
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
Background summary
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 GABA-ergic anaesthetics
and reduction of delirium In 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.
Study objective
Primary objective:
Plasma levels of clonidine, in order to describe pharmacokinetic and
pharmacodynamic properties of intravenous clonidine in critically ill
ventilated ICU patients.
Secondary objectives are:
* to evaluate the effect of a 3-hr loading schedule on serum levels and the
time to reach steady state concentrations
* Plasma clonidine concentrations in patients with impaired renal function,
renal replacement therapy and in patients with an altered distribution volume
* Hemodynamic parameters
* Sedation levels
Study design
This study is a single centre, prospective, open-label, non-randomized, dose
escalation cohort study in 32 ICU patients.
Intervention
Clonidine is added to standard sedation at the time of first interruption of
sedation. Three cohorts of eight will receive continuous infusions of iv
clonidine in doses of 600, 1200, and 1800 µg/24h. The first half of each dosing
group will not receive a loading dose and the second half will receive a
loading dose of intravenous clonidine (triple infusion velocity during four
hours). A fourth cohort with 8 patients will receive no clonidine, and serves
as a control group
Study burden and risks
The burden associated with participation is minimal. Once daily blood samples,
CAM-ICU scales, RASS scales and physical examinations required for the study
are all routine daily practice on the ICU. Extra blood samples will be taken
for pharmacokinetic modelling (7 + once daily from day 1 until end of
infusion). Blood samples will be drawn from arterial catheters already in
place. The addition of clonidine for sedation of critically ill patients is
common practice in many ICU*s in the Netherlands and is generally thought to be
safe. Although clonidine can cause hypotension and bradycardia, this is not
considered a safety risk in a monitored environment.
The benefit of participation is the possibility to reduce the period of
delirium during ICU stay. The relevance of this study lies in the widespread
off-label use of clonidine in critically ill patients and the lack of consensus
on administration and dosing. The purpose of this study is to develop a dosing
regimen to achieve sufficient sedation without significant cardiovascular side
effects.
Nico Bolkesteinlaan 75
Deventer 7416SE
NL
Nico Bolkesteinlaan 75
Deventer 7416SE
NL
Listed location countries
Age
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.
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
When renal failure (eGFR <30ml/min): maximum dose of clonidine will be 1200mcg
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-001699-23-NL |
| ClinicalTrials.gov | NCT02466373 |
| CCMO | NL53097.075.15 |