Efficacy, Safety and Pharmacokinetic Study of Intravenous Clonidine Versus Midazolam for Sedation in Paediatric Patients
Information source: University of Erlangen-Nürnberg Medical School
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Sedation in Intensive Care
Intervention: Clonidine (Drug); Midazolam (Drug)
Phase: Phase 3
Status: Not yet recruiting
Sponsored by: University of Erlangen-Nürnberg Medical School Overall contact: Antje Neubert, PhD Assoc Prof, Phone: +49 9131 8541203, Email: paed-studienzentrale@uk-erlangen.de
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 tracheal
intubation and mechanical ventilation. 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.
Clinical Details
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
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Primary outcome: Sedation failure
Secondary outcome: Pharmacokinetics/Pharmacodynamics (PKPD) modeling (measured by plasma concentrations and sedation score results (COMFORT-B)Safety assessment (number of patients with adverse events) Extent of withdrawal effects Extent of rebound hypertension Percentage of respiratory depression per group Neurodevelopment (Bayley Scales of Infant Development, Second Edition (Bayley-II) score) Pharmacogenomic assessment (measured by plasma concentrations and candidate gene polymorphisms/genotyping)
Eligibility
Minimum age: N/A.
Maximum age: 18 Years.
Gender(s): Both.
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 1200 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
- Subjects who have already received clonidine as a sedative agent within the last 7
days prior to admission to PICU
- 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 being treated with forbidden concomitant medications (e. g. continuous
infusion of muscle relaxants; defined in the protocol)
- 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 continuous positive airway pressure (CPAP)
- Subjects currently being treated with Extra Corporeal Membrane Oxygenation (ECMO)
- Subjects with treatment-induced whole body hypothermia
- Subjects with severe organ insufficiencies
- Subjects with traumatic brain injury all grades (due to potential effects on the
level of consciousness)
- Subjects with intracranial pathology (tumour, haemorrhage, infections) with an effect
on level of consciousness
- Subjects with severe mental retardation with or without a well-defined syndrome that
preclude performance of a COMFORT-B Score
- Subjects with Myasthenia gravis, Spinal muscular atrophy, or other rare neurologic
diseases and conditions which that preclude performance of a COMFORT-B Score
- Subjects with major congenital anomalies of the central nervous system
- Subjects with phaeochromocytoma.
- Subjects with severe bradyarrhythmia resulting from either sick-sinus syndrome or
atrioventricular (AV) block of 2nd or 3rd degree
- Subjects with current status epilepticus or active fitting (2 or more seizures
regularly on a daily basis) at admission
- Subjects with acute asthma
- Subjects with paralytic ileus
- 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
- 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, country-specific guidelines are given in the protocol
Locations and Contacts
Antje Neubert, PhD Assoc Prof, Phone: +49 9131 8541203, Email: paed-studienzentrale@uk-erlangen.de
Univerzita Karlova v Praze, Prague 121 09, Czech Republic; Not yet recruiting Kristýna Matějková, DiS Pavla Pokorna, MD, Principal Investigator
University of Erlangen-Nürnberg Medical School, Erlangen 91054, Germany; Not yet recruiting Evelin Muschiol, Phone: +49 9131 85-41203, Email: evelin.muschiol@uk-erlangen.de Thomas MK Völkl, MD, Principal Investigator
Bambino Gesù Hospital and Research Institute, Rome 00165, Italy; Not yet recruiting Piero David, MD, Email: piero.david.md@gmail.com Alessandra Simonetti, MD, Principal Investigator
Karolinska Institutet, Stockholm 17176, Sweden; Not yet recruiting Peter Larsson, MD, PhD, Phone: +46851777269, Email: peter.larsson@karolinska.se Johan Fenhammar, MD, PhD, Phone: +46851773735, Email: johan.fenhammar@karolinska.se Jonas Berner, MD, PhD, Principal Investigator
Erasmus Medical Center, Rotterdam, Zuid-Holland 3015 CN, Netherlands; Not yet recruiting Manuel Baarslag, MD, Phone: +31 10 703 75 94, Email: m.baarslag@erasmusmc.nl Dick Tibboel, MD Prof, Principal Investigator
Additional Information
Starting date: September 2015
Last updated: July 27, 2015
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