ARITMO
The ARITMO project (full title: “Arrhythmogenic Potential of Drugs”) is funded by the European Commission in the 7th Framework Programme, coordinated by Professor Dr. Miriam Sturkenboom of Erasmus Universitair Medisch Centrum (Netherlands), and carried out by a consortium of 17 leading research institutions.
The ARITMO project aims to analyse the arrhythmic potential of drugs in the following classes: antipsychotics, anti-infectives (antibacterials, antimycotics and antivirals) and H1-antihistamines, globally and in specific subgroups (age, co-morbidity, genetically).
The strategy to be followed consists of using existing data and generating a wealth of new data through field, database and in silico studies. From the literature and a variety of databases, information on the risk of QTc prolongation, Torsade de Pointes (TdP), ventricular fibrillation and sudden death will be obtained and analysed at a pre-clinical, clinical and post-marketing level. An international prospective case-control surveillance network will run in UK, Germany, Italy and Netherlands and will collect data on risk factors as well as blood samples for candidate gene analyses. These data collections will be harmonized, extended and continued during the study and will provide unique opportunities to assess both the associations with specific drugs as well as the interaction with genetic factors. Finally, all information generated will be integrated in order to provide lists that will allow the ranking of the arrhythmic potential of antihistamines, antipsychotics and anti-infective drugs by selected parameters.
The DSRU are involved primarily with two aspects of the ARITMO project:
Ongoing observational study:
The DSRU, as partners with St. George’s, University of London (SGUL), will provide the database and administrative infrastructure for the cohort and case-control study and the genetic analysis at SGUL. This is as a continuation of the Drug-induced Arrhythmia Risk Evaluation (DARE) Study, originally formed for the prospective observational case- control study of Drug Induced Arrhythmia, funded by the British Heart Foundation. The DARE network has received ethical approval for continuation of collection of further prospective cases of prolonged QT and Torsades de Pointes associated with drugs for epidemiological and anonymised genetic analysis.
Systematic review of existing literature:
The DSRU in partnership with colleagues from the Universities of Newcastle (UK), Bologna (Italy) and Victor-Segalen Bordeaux (France) are performing a systematic review of evidence from pre-clinical, clinical trial and observational studies from the published literature for the arrhythmogenic potential (QT/TdP) liability of the drugs of interest (approximately 220 compounds).
List of of all ARITMO partners:
· Erasmus Universitair Medisch Centrum Rotterdam (Netherlands) - Coordinator
· Fundació IMIM (Spain)
· London School of Hygiene and Tropical Medicine (UK)
· Alma Mater Studiorum (Italy)
· Universitaet Bremen (Germany)
· University of Newcastle (UK)
· Université Victor-Segalen Bordeaux II (France)
· Fondazione Salvatore Maugeri Clinica del Lavoro e Della Riabilitazione (Italy)
· Charite - Universitaetsmedizin Berlin (Germany)
· Università Degli Studi di Verona (Italy)
· St. George's Hospital Medical School (UK)
· Astra Zeneca AB (Sweden)
· PHARMO Coöperatie UA (Netherlands)
· Fondazione Scientifica SIMG-ONLUS (Italy)
· Aarhus Univesitetshospital, Aarhus Sygehus (Denmark)
· Academisch Medisch Centrum bij de Universiteit van Amsterdam (Netherlands)
· Drug Safety Research Trust (UK)