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Trial record 84 of 326 for:    clonidine

Efficacy, Safety and Pharmacokinetic Study of Intravenous Clonidine Versus Midazolam for Sedation in Paediatric Patients (CloSed1)

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ClinicalTrials.gov Identifier: NCT02509273
Recruitment Status : Terminated (lack of recruitment)
First Posted : July 28, 2015
Last Update Posted : January 9, 2019
Sponsor:
Collaborators:
Erasmus Medical Center
University of Tartu
Therakind Ltd
Gianni Benzi Pharmacological Research Foundation
University College, London
Karolinska Institutet
Univerzita Karlova v Praze
Vereniging Samenwerkende Ouder- En Patientenorganisaties
Bambino Gesù Hospital and Research Institute
European Commission
ARNAS Civico Di Cristina Benfratelli Hospital
Servicio Madrileño de Salud, Madrid, Spain
Information provided by (Responsible Party):
University of Erlangen-Nürnberg Medical School

Brief Summary:

Closed1 aims to compare the efficacy, safety and pharmacokinetics of clonidine (hydrochloride) to midazolam in the sedation of ventilated children and adolescents (0-18 years) admitted to a paediatric intensive care unit (PICU) and requiring mechanical ventilation and sedation for at least 24 hours.

In particular, the proportion of subjects with sedation failure at the maximum possible dose (defined within the study protocol) will be measured. Additionally, the safety and tolerability (including withdrawal effects) of clonidine compared to midazolam will be evaluated. A pharmacokinetic-pharmacodynamic relationship of clonidine for sedation in PICU will be established. Genetic polymorphisms of clinical relevance affecting pharmacokinetics, pharmacodynamics and metabolism will be also identified.

Ad hoc paediatric parenteral formulations of clonidine hydrochloride and midazolam will be manufactured. At least 300 subjects will be enrolled from study centres in five European member countries (Czech Republic, Germany, Italy, the Netherlands, and Sweden).

The clinical study will enrol critically ill paediatric patients who require mechanical ventilation and sedation.

Subjects will be closely followed using standard PICU monitoring of vital functions (continuous assessment of heart rate and peripheral arterial oxygen saturation, intermittent assessment of systolic and diastolic blood pressure), intermittent assessment of pain and depth of sedation, documentation of parameters of mechanical ventilation and intermittent arterial blood gas analysis.

The study will be conducted in compliance with the study protocol, Good Clinical Practice (ICH-GCP) and the applicable regulatory requirement(s). In addition, qualified PICU staff will be monitoring subjects around the clock, thus minimising reaction time in case of alarms or deterioration of clinical parameters.

This project has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement n° 602453.


Condition or disease Intervention/treatment Phase
Sedation in Intensive Care Drug: Clonidine Drug: Midazolam Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Double Blind, Randomised, Multicentre, Active Controlled, Parallel-group, Phase III Trial to Evaluate the Efficacy, Safety and Pharmacokinetics of Intravenous Clonidine (Hydrochloride) Compared to Midazolam for Sedation in Children From Birth to Less Than 18 Years of Age
Actual Study Start Date : May 2016
Actual Primary Completion Date : October 2018
Actual Study Completion Date : October 22, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: CLONIDINE HYDROCHLORIDE
solution for i.v. infusion (maximum 55 μg/kg per day; maximum 7 day treatment)
Drug: Clonidine
Active Comparator: MIDAZOLAM
solution for i.v. infusion (maximum 5.5 mg/kg per day; maximum 7 day treatment)
Drug: Midazolam



Primary Outcome Measures :
  1. Sedation failure [ Time Frame: ≤ 7 days ]
    measured by pain score Numerical Rating Scale (NRS), sedation score COMFORT-B and sedation score Nurse's Interpretation of Sedation (NISS)


Secondary Outcome Measures :
  1. Pharmacokinetics/Pharmacodynamics (PKPD) modeling (measured by plasma concentrations and sedation score results (COMFORT-B) [ Time Frame: ≤ 7 days treatment period ]
    measured by plasma concentrations and sedation score results (COMFORT-B)

  2. Safety assessment (number of patients with adverse events) [ Time Frame: ≤ 21 ± 2 days (treatment period, completion visit, post dose monitoring and follow-up visit) in all subjects ]
    measured by number of patients with adverse events

  3. Extent of withdrawal effects [ Time Frame: post dose ≥ 1 day, ≤ 5 days ]
    measured by score Sophia Observation Withdrawal Symptoms-Paediatric Delirium (SOS-PD)

  4. Extent of rebound hypertension [ Time Frame: post dose ≥ 3 days, ≤ 5 days ]
    measured by blood pressure assessment for at least 72 hours after IMP cessation

  5. Percentage of respiratory depression per group [ Time Frame: during re-intubation apnoea in treatment period (≤ 7 days), post dose monitoring every 24 hours up to 10 days ]
    Number of reintubations / number extubation failures ratio %

  6. Neurodevelopment (Bayley Scales of Infant Development, Second Edition (Bayley-II) score) [ Time Frame: 1 year (in neonates only) ]
    Bayley Scales of Infant Development, Second Edition (Bayley-II) score

  7. Pharmacogenomic assessment (measured by plasma concentrations and candidate gene polymorphisms/genotyping) [ Time Frame: On 1 day of treatment period (≤7 days) only ]
    measured by plasma concentrations and candidate gene polymorphisms/genotyping



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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or Female
  • Aged from birth (≥34 weeks gestational age [GA]) to <17 years, 11 months, 1 week old
  • Admitted or expected to be admitted (post-operatively) to PICU
  • Existing or expected indication for invasive or non-invasive ventilation (except Continuous Positive Airway Pressure, CPAP)
  • Anticipated need for continuous sedation for at least 24 hours
  • Informed consent (or deferred consent) obtained from the subject's parent(s) or legal guardian(s)
  • Where applicable, assent obtained from the subject to participate in the clinical trial

Exclusion Criteria:

  • Body weight less than 1500 g
  • Gestational age [GA] of <34 weeks
  • Body weight 3 kg or less AND aged 28 days or older
  • Body weight less than 10 kg AND aged 2 years old or older
  • Body weight greater than 85 kg
  • Subjects who will be 18 years old in less than 3 weeks
  • Known hypersensitivity to the IMP (clonidine) or comparator (midazolam), or Non Investigational Medicinal Product (morphine, propofol) or any of their formulation ingredients and their rescue medication
  • Subjects anticipated to be treated with forbidden concomitant medications during IMP administration
  • Subjects less than 24 hours post-resuscitation
  • Subjects who have been under sedation for more than 72 hours immediately prior to assessment
  • Subjects currently being treated with Extra Corporeal Membrane Oxygenation (ECMO)
  • Subjects with treatment-induced whole body hypothermia
  • Subjects with severe organ insufficiencies
  • Subjects whose condition is assessed by the investigator to have an effect on the level of consciousness which impairs the assessment of sedation (COMFORT-B/NISS)
  • Subjects with phaeochromocytoma
  • Subjects with severe bradyarrhythmia resulting from either sick-sinus syndrome or atrioventricular (AV) block of 2nd or 3rd degree
  • Known arterial hypertension requiring chronic treatment in medical history
  • Females who are pregnant, lactating or planning to become pregnant or who return a positive result to a urine pregnancy test (a dipstick and serum pregnancy test will be performed at the screening visit).
  • Employee or direct relative of an employee or any member of the study site staff or the Sponsor/ study management staff (applies to subject and/ or subject's parent(s)
  • Participation in a clinical intervention study using drugs within the last 3 weeks
  • Previous participation in this clinical study at any time
  • Parent(s)/ legal guardian(s) decline to give informed consent. If parent(s)/ legal guardian(s) are not present

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): NCT02509273


Locations
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Czechia
Univerzita Karlova v Praze
Prague, Czechia, 121 09
Estonia
Tallinn Children`s Hospital
Tallinn, Estonia
Germany
University of Erlangen-Nürnberg Medical School
Erlangen, Germany, 91054
Diakonie Neuendettelsau - Cnopf'sche Kinderklinik Nürnberg
Nürnberg, Germany
Italy
Azienda Ospedaliero Universitaria Policlinico di Bari
Bari, Italy, 70124
ARNAS Civico Di Cristina Benfratelli
Palermo, Italy, 90127
Bambino Gesù Hospital and Research Institute
Rome, Italy, 00165
Netherlands
Erasmus Medical Center
Rotterdam, Zuid-Holland, Netherlands, 3015 CN
Spain
Hospital Universitario 12 de Octubre
Madrid, Spain, 28041
Sweden
Karolinska Institutet
Stockholm, Sweden, 17176
Sponsors and Collaborators
University of Erlangen-Nürnberg Medical School
Erasmus Medical Center
University of Tartu
Therakind Ltd
Gianni Benzi Pharmacological Research Foundation
University College, London
Karolinska Institutet
Univerzita Karlova v Praze
Vereniging Samenwerkende Ouder- En Patientenorganisaties
Bambino Gesù Hospital and Research Institute
European Commission
ARNAS Civico Di Cristina Benfratelli Hospital
Servicio Madrileño de Salud, Madrid, Spain

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University of Erlangen-Nürnberg Medical School
ClinicalTrials.gov Identifier: NCT02509273     History of Changes
Other Study ID Numbers: CLON01
2014-003582-24 ( EudraCT Number )
First Posted: July 28, 2015    Key Record Dates
Last Update Posted: January 9, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Additional relevant MeSH terms:
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Clonidine
Midazolam
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents