The majority of critically ill children admitted to the Paediatric Intensive Care Unit (PICU) require sedation and analgesia, which are commonly achieved with agents showing a significant side-effect profile.
Clonidine is a drug authorised for use throughout the EU and the USA as a centrally acting hypotensive agent (in adults only) and a treatment for migraines (in adults and children over 12 years only), and in the USA for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children aged 6 to 17 years. In addition to its approved indications, clonidine is commonly used off-label in paediatric anaesthesia and intensive care medicine. Its effects reduce intraoperative anaesthetic requirements and metabolic responses to surgery. UK and German consensus guidelines and local hospital guidelines across Europe recommend clonidine in sedation in critically ill children in PICUs.
Despite this widespread use, the effectiveness, optimal dose requirements and safety of clonidine have not been fully studied in paediatrics. For these reasons, clonidine has been included in the 2012 EMA Revised Priority List for Studies into Off-Patent Paediatric Medicinal Products. According to this document, paediatric data on pharmacokinetics, efficacy and safety and age-appropriate formulations are requested for clonidine in the treatment of pain and sedation in PICUs. Furthermore, EMA identified need in the field of anaesthesiology of data on safety and efficacy in long-term analgosedation on ICUs, data on parenteral and epidural use in children and age appropriate formulation [Doc Ref EMEA/405166/2006].
CloSed is expected to fill these gaps, since it is aimed to develop and test a parenteral age-appropriate formulation of clonidine for sedation in PICU and to obtain a Paediatric Use Marketing Authorisation (PUMA).
A Paediatric Investigation Plan (PIP) with a comprehensive development plan for clonidine is already available and the new formulation will be studied in a randomised, double-blind, active comparator controlled clinical trial in neonates and children to provide evidence-based data on its safety and efficacy.
Research will be conducted in line with the ethical requirements in the paediatric population, considering risk minimisation for patients, avoiding unnecessary studies and make use of already available data as it has been outlined both in the Paediatric Regulation (EC No 1901/20061) and in the Ethical considerations for clinical trials on medicinal products conducted with the paediatric population (EC, 20082).