Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 4 of 328 for:    clonidine

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE April 21, 2015
First Posted Date  ICMJE June 9, 2015
Last Update Posted Date July 30, 2018
Study Start Date  ICMJE December 2016
Actual Primary Completion Date April 5, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 9, 2015)
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).
Original Primary Outcome Measures  ICMJE
 (submitted: June 4, 2015)
clonidine plasma concentrations [ Time Frame: 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).
Change History Complete list of historical versions of study NCT02466373 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 9, 2015)
  • heart rate [ Time Frame: up to 7 days ]
    Heart rate 2-hrly for the first 12 h, 8-hrly thereafter
  • blood pressure [ Time Frame: up to 7 days ]
    Blood pressure 2-hrly for the first 12 h, 8-hrly thereafter
  • delirium [ Time Frame: up to 7 days ]
    delirium rating scale, CAM-ICU 3 times daily
  • use of antipsychotics [ Time Frame: up to 7 days ]
    additional use of haloperidol or sedatives, measured in total amount during the investigational period
Original Secondary Outcome Measures  ICMJE
 (submitted: June 4, 2015)
  • heart rate [ Time Frame: 7 days ]
    Heart rate 2-hrly for the first 12 h, 8-hrly thereafter
  • blood pressure [ Time Frame: 7 days ]
    Blood pressure 2-hrly for the first 12 h, 8-hrly thereafter
  • delirium [ Time Frame: 7 days ]
    delirium rating scale, CAM-ICU 3 times daily
  • use of antipsychotics [ Time Frame: 7 days ]
    additional use of haloperidol or sedatives, measured in total amount during the investigational period
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacokinetics and Clinical Effects of Escalating Doses of Clonidine in ICU Patients
Official Title  ICMJE Pharmacokinetics and Clinical Effects of Escalating Doses of Clonidine in ICU Patients
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Delirium
  • Critical Illness
Intervention  ICMJE Drug: Clonidine (Catapresan®) 0,150 mg/ml, ampoule 1 ml
clonidine intravenous
Other Name: Boehringer Ingelheim, RVG 06055
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Clonidine (Catapresan®) 0,150 mg/ml, ampoule 1 ml
  • 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.
    Intervention: Drug: Clonidine (Catapresan®) 0,150 mg/ml, ampoule 1 ml
  • 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.
    Intervention: Drug: Clonidine (Catapresan®) 0,150 mg/ml, ampoule 1 ml
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 4, 2015)
32
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE April 5, 2018
Actual Primary Completion Date April 5, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02466373
Other Study ID Numbers  ICMJE Clonidine kinetics 1.1
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party M. Zeeman, Deventer Ziekenhuis
Study Sponsor  ICMJE Deventer Ziekenhuis
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Huub Oever v/d Deventer Ziekenhuis
PRS Account Deventer Ziekenhuis
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP