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
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|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||28 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|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|
Experimental: CLONIDINE HYDROCHLORIDE
solution for i.v. infusion (maximum 55 μg/kg per day; maximum 7 day treatment)
Active Comparator: MIDAZOLAM
solution for i.v. infusion (maximum 5.5 mg/kg per day; maximum 7 day treatment)
- 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)
- 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
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02509273
|Univerzita Karlova v Praze|
|Prague, Czechia, 121 09|
|Tallinn Children's Hospital|
|University of Erlangen-Nürnberg Medical School|
|Erlangen, Germany, 91054|
|Diakonie Neuendettelsau - Cnopf'sche Kinderklinik Nürnberg|
|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|
|Erasmus Medical Center|
|Rotterdam, Zuid-Holland, Netherlands, 3015 CN|
|Hospital Universitario 12 de Octubre|
|Madrid, Spain, 28041|
|Stockholm, Sweden, 17176|