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Trial record 4 of 326 for:    clonidine

Pharmacokinetics and Clinical Effects of Escalating Doses of Clonidine in ICU Patients (Clokin1)

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ClinicalTrials.gov Identifier: NCT02466373
Recruitment Status : Completed
First Posted : June 9, 2015
Last Update Posted : July 30, 2018
Sponsor:
Information provided by (Responsible Party):
M. Zeeman, Deventer Ziekenhuis

Brief 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.

Condition or disease Intervention/treatment Phase
Delirium Critical Illness Drug: Clonidine (Catapresan®) 0,150 mg/ml, ampoule 1 ml Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pharmacokinetics and Clinical Effects of Escalating Doses of Clonidine in ICU Patients
Study Start Date : December 2016
Actual Primary Completion Date : April 5, 2018
Actual Study Completion Date : April 5, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Delirium

Arm Intervention/treatment
No Intervention: No clonidine
No clonidine is administered. The outcome measures are recorded, to compare them with the outcome measures of the other clonidine arms
Experimental: Clonidine 600mcg
4 patients receive 600 µg/day of clonidine without loading schedule. 4 patients receive 600 µg/day of clonidine with a loading schedule of 300 µg in 4 h.
Drug: Clonidine (Catapresan®) 0,150 mg/ml, ampoule 1 ml
clonidine intravenous
Other Name: Boehringer Ingelheim, RVG 06055

Experimental: Clonidine 1200mcg
  • 4 patients receive 1200 µg/day of clonidine without loading schedule.
  • 4 patients receive 1200 µg/day of clonidine with a loading schedule of 600 µg in 4 h.
Drug: Clonidine (Catapresan®) 0,150 mg/ml, ampoule 1 ml
clonidine intravenous
Other Name: Boehringer Ingelheim, RVG 06055

Experimental: Clonidine 1800mcg
  • 4 patients receive 1800 µg/day of clonidine without loading schedule.
  • 4 patients receive 1800 µg/day of clonidine with a loading schedule of 900 µg in 4 h.
Drug: Clonidine (Catapresan®) 0,150 mg/ml, ampoule 1 ml
clonidine intravenous
Other Name: Boehringer Ingelheim, RVG 06055




Primary Outcome Measures :
  1. clonidine plasma concentrations [ Time Frame: up to 7 days ]
    pharmacokinetic and pharmacodynamic properties of intravenous clonidine in ICU patients 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).


Secondary Outcome Measures :
  1. heart rate [ Time Frame: up to 7 days ]
    Heart rate 2-hrly for the first 12 h, 8-hrly thereafter

  2. blood pressure [ Time Frame: up to 7 days ]
    Blood pressure 2-hrly for the first 12 h, 8-hrly thereafter

  3. delirium [ Time Frame: up to 7 days ]
    delirium rating scale, CAM-ICU 3 times daily

  4. use of antipsychotics [ Time Frame: up to 7 days ]
    additional use of haloperidol or sedatives, measured in total amount during the investigational period



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02466373


Locations
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Netherlands
Deventer Hospital
Deventer, Netherlands
Sponsors and Collaborators
Deventer Ziekenhuis
Investigators
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Principal Investigator: Huub Oever v/d Deventer Ziekenhuis

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Responsible Party: M. Zeeman, drs M. Zeeman, Deventer Ziekenhuis
ClinicalTrials.gov Identifier: NCT02466373     History of Changes
Other Study ID Numbers: Clonidine kinetics 1.1
First Posted: June 9, 2015    Key Record Dates
Last Update Posted: July 30, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by M. Zeeman, Deventer Ziekenhuis:
clonidine
pharmacodynamics
pharmacokinetics
intensive care
delirium
Additional relevant MeSH terms:
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Clonidine
Delirium
Critical Illness
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Neurocognitive Disorders
Mental Disorders
Disease Attributes
Pathologic Processes
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action