CLOSED · Clonidine for Sedation of Paediatric Patients in the Intensive Care Unit

The majority of critically ill children admitted to Paediatric Intensive Care Units (PICU) will require sedationand analgesia which is commonly achieved with a combination of an benzodiazepine and an opioid. However,these agents have a significant side-effect profile, including tolerance, withdrawal and respiratory/circulatorydepression. Clonidine is commonly used for sedation in PICU and recommended by guidelines in variouscountries although there is a lack of evidence regarding it safety and efficacy in this setting. The need for safetyand efficacy data as well as an age appropriate formulation for clonidine has been realised and clonidine isincluded in the EMA “Revised Priority List for Studies into Off-patent Medicinal Products”. Thus this proposaladdresses an important paediatric therapeutic need. It is designed to fullfill the requirements for most ethicalresearch in the paediatric population considering risk minimisation for patients, avoiding unnecessary studies andmake use of already available data as outlined in the Paediatric Regulation (EC) No 1901/2006. The objectivesof this project are a) to develop an age appropriate formulation of clonidine suitable for sedation of children inPICU b) to conduct a randomised, phase III, double-blind, active-controlled parallel group clinical trial of clonidinevs midazolam in patients from birth to 18 years to establish the efficacy and safety, including long-term outcomesand dose-dependent effects of clonidine and c) to establish an European consensus guideline for sedion ofcritically ill children. The ultimate goal is to use these data and to apply for a PUMA. On this basis a PaediatricInvestigation Plan (PIP) has been approved by the EMA in February 2013 and is reflected in the work plan ofCloSed. The project will increase the availability of paediatric medicines, foster the conduct of clinical trials inchildren and establish international paediatric research collaborations.