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

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.

Conditions

• Sedation in Intensive Care

Interventions

DRUG

Clonidine

DRUG

Midazolam

Sponsors & Collaborators

• Erasmus Medical Center

  collaborator OTHER

• University of Tartu

  collaborator OTHER

• Therakind Ltd

  collaborator UNKNOWN

• Gianni Benzi Pharmacological Research Foundation

  collaborator OTHER

• University College, London

  collaborator OTHER

• Karolinska Institutet

  collaborator OTHER

• Univerzita Karlova v Praze

  collaborator OTHER

• Vereniging Samenwerkende Ouder- En Patientenorganisaties

  collaborator UNKNOWN

• Bambino Gesù Hospital and Research Institute

  collaborator OTHER

• European Commission

  collaborator OTHER

• ARNAS Civico Di Cristina Benfratelli Hospital

  collaborator OTHER

• Servicio Madrileño de Salud, Madrid, Spain

  collaborator OTHER

• University of Erlangen-Nürnberg Medical School

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Max Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-05-31

Primary Completion

2018-10-31

Completion

2018-10-22

Countries

• Czechia
• Estonia
• Germany
• Italy
• Netherlands
• Spain
• Sweden

Study Locations