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Trial record 86 of 304 for:    clonidine

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

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: 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

Tracking Information
First Submitted Date  ICMJE April 27, 2015
First Posted Date  ICMJE July 28, 2015
Last Update Posted Date January 9, 2019
Actual Study Start Date  ICMJE May 2016
Actual Primary Completion Date October 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 27, 2015)
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)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 27, 2015)
  • 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)
  • 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
  • Extent of withdrawal effects [ Time Frame: post dose ≥ 1 day, ≤ 5 days ]
    measured by score Sophia Observation Withdrawal Symptoms-Paediatric Delirium (SOS-PD)
  • 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
  • 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 %
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy, Safety and Pharmacokinetic Study of Intravenous Clonidine Versus Midazolam for Sedation in Paediatric Patients
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Sedation in Intensive Care
Intervention  ICMJE
  • Drug: Clonidine
  • Drug: Midazolam
Study Arms  ICMJE
  • Experimental: CLONIDINE HYDROCHLORIDE
    solution for i.v. infusion (maximum 55 μg/kg per day; maximum 7 day treatment)
    Intervention: Drug: Clonidine
  • Active Comparator: MIDAZOLAM
    solution for i.v. infusion (maximum 5.5 mg/kg per day; maximum 7 day treatment)
    Intervention: Drug: Midazolam
Publications * Neubert A, Baarslag MA, Dijk MV, Rosmalen JV, Standing JF, Sheng Y, Rascher W, Roberts D, Winslade J, Rawcliffe L, Hanning SM, Metsvaht T, Giannuzzi V, Larsson P, Pokorná P, Simonetti A, Tibboel D; CLOSED Consortium. The CLOSED trial; CLOnidine compared with midazolam for SEDation of paediatric patients in the intensive care unit: study protocol for a multicentre randomised controlled trial. BMJ Open. 2017 Jun 21;7(6):e016031. doi: 10.1136/bmjopen-2017-016031. Erratum in: BMJ Open. 2017 Nov 8;7(11):e016031corr1.

*   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 Terminated
Actual Enrollment  ICMJE
 (submitted: January 7, 2019)
28
Original Estimated Enrollment  ICMJE
 (submitted: July 27, 2015)
300
Actual Study Completion Date  ICMJE October 22, 2018
Actual Primary Completion Date October 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Czechia,   Estonia,   Germany,   Italy,   Netherlands,   Spain,   Sweden
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT02509273
Other Study ID Numbers  ICMJE CLON01
2014-003582-24 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party University of Erlangen-Nürnberg Medical School
Study Sponsor  ICMJE University of Erlangen-Nürnberg Medical School
Collaborators  ICMJE
  • 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
Investigators  ICMJE Not Provided
PRS Account University of Erlangen-Nürnberg Medical School
Verification Date January 2019

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