CloSed is organised in the following work packages:
The objective of this WP is to coordinate and manage the project in order to achieve the objectives and perform the planned activities on time and according to the applicable rules defined by DG Research with regards to FP7 programs and the legal obligations associated with the research. All participants in the project are advised and guided to comply with the EU regulations and their contractual and legal requirements. An efficient communication between participants and with the European Commission (EC) is ensured.
WP Leader: Bernd Gebhardt, UKER
Involved Partners: UKER, FGB
The overall purpose of this WP is to ensure oversight, coordination and monitoring of the whole research programme from a scientific perspective, in order to successfully deliver the CloSed project’s research commitments. The Project Scientific Coordination ensures that the clinical trial adheres to international standards and requirements, including “Good Clinical Practice” (GCP).
WP Leader: Antje Neubert, UKER
Involved Partners: UKER, Therakind, EMC
The project aims to develop formulations of medicines suitable for the paediatric population in order to accurately administer the dose range proposed: 3 different strengths of clonidine and midazolam IV formulations (the so-called “Investigational Medicinal Products” – IMPs) that can be blinded during the clinical trial in accordance with GMP (Good Manufacturing Practices) and GCP standards.
WP Leader: Cathérine Tuleu, UCL
Involved Partners: UCL, UKER, Therakind
This WP is concerned with the statistical aspects of the trial and with the development of a PK-PD model of clonidine. This is aimed to ascertain the relative efficacy of clonidine vs. midazolam and to recommend starting doses for IV clonidine for sedation and clinically useful ranges for infusion during the clinical trial.
WP Leader: Joe Standing, UCL
Involved Partners: UCL, EMC, KI, UTARTU
This WP will design and conduct a prospective, multicentre, double-blind, randomised, active-controlled, clinical trial of clonidine vs midazolam in children and adolescents from birth to <18 years (excluding preterms) admitted to PICU.
WP Leader: Dick Tibboel, EMC
Involved Partners: UKER, EMC, KI, UTARTU, CUNI, OPBG
The clinical trial and the Marketing Authorisation Application (MAA) require specific regulatory requirements. For instance, the clinical trial must be submitted to competent ethical committees and national authorities, and it is necessary to maintain this authorisation for all the duration of the study. Importantly, the development programme is to be compliant with the PIP, and all the communications with the EMA/PDCO will be co-ordinated and managed up to the validation check stage in order to apply for a PUMA.
WP Leader: Jackie Winslade, Therakind
Involved Partners: Therakind, UCL, FGB
All medical-ethical considerations are integrated in CloSed in general and into the clinical trial in particular, which involves children from five different European countries. Therefore, the conduct of the study poses a series of ethical challenges that the project is going to face, and requires that the ICH guideline on Good Clinical Practice (GCP) and all applicable international and national rules be followed. This WP also coordinates the activities of the two internal bodies set up within the project – the Independent Scientific Advisory Board (ISAB) and the Patient Advisory Board (PAB) – to advice on ethical issues and training of partners and investigators to the ethical standards to be met in this research.
WP Leader: Tuuli Metsvaht, UTARTU
Involved Partners: UTARTU, UKER, UCL, Therakind, EMC, FGB, KI, CUNI, VSOP, OPBG
This WP coordinates the external relationships and all dissemination activities regarding the progress and the results of CloSed to public and professional communities, stakeholders and researchers. Consensus guidelines for sedation in critically ill newborns and children will be developed and made available, as well as scientific publications.
WP Leader: Viviana Giannuzzi, FGB
Involved Partners: FGB, UKER, Therakind, EMC, VSOP
The overall objective of this WP is to establish a robust quality assurance (QA) and quality control (QC) system to ensure and verify that the clinical trial is conducted in accordance with the study protocol and in compliance with the Declaration of Helsinki, the principles of ICH-GCP and all applicable legal and regulatory requirements. The QA/QC system comprises three distinct groups of objectives/tasks: a) Establish formal procedures (SOPs) for the study conduct b) Conduct Clinical monitoring activities c) Establish Data Monitoring Committee d) Perform audit activities
WP Leader: Susan Conroy, Therakind
Involved Partners: Therakind, UKER, EMC