Microsoft word - contemporary clinical trials.docx

Volume 32, Issue 5, September 2011, Pages 675-684 The GiSAS study: Rationale and design of a pragmatic randomized controlled trial on aripiprazole, olanzapine and haloperidol in the long-term treatment of schizophrenia ☆  a Epidemiology and Social Psychiatry Unit, 'Mario Negri' Institute for Pharmacological Research, Via La Masa 19, 20156 Milan, Italy  b Laboratory of Geriatric Neuropsychiatry, 'Mario Negri' Institute for Pharmacological Research, Via La Masa 19, 20156 Milan, Italy  Received 25 November 2010. Revised 29 March 2011. Accepted 21 April 2011. Available online 30 April 2011.  http://dx.doi.org/10.1016/j.cct.2011.04.008, How to Cite or Link Using DOI  Cited by in Scopus (0) Given the controversy about the comparative efficacy of first- compared with second-generation antipsychotics in the treatment of schizophrenia, more large-scale evidence is needed to guide clinicians in their prescriptions. Most randomized controlled trials (RCTs) were conducted in centers of excellence on highly selected samples, poorly representative of real-world patients, and often suffered conflicts of interest as they were sponsored by drug companies. The primary aim of the present study is to compare the effectiveness of haloperidol, olanzapine and aripiprazole in a representative sample of schizophrenia patients. The GiSAS trial is an open-label, independent, pragmatic RCT in Italian community-based public psychiatric services. At least 260 patients meeting the DSM-IV criteria for schizophrenia will be randomly allocated to one of the study drugs and followed up for one year. A two-year observational phase will follow. The primary outcome for tolerability will be the onset of metabolic syndrome. The primary endpoint for effectiveness will be discontinuation of antipsychotic monotherapy. Secondary measures include global functioning, time to discontinuation due to side-effects, change of lipid profile, extrapyramidal symptoms and other adverse effects. In the last four years, the GiSAS study group has been working to implement this multicenter RCT. The trial mechanism is now fully functional and working. As of end of February 2011, 260 subjects were randomized by 54 study investigators in 33 out of 43 participating centers.  Antipsychotic;  Schizophrenia;  Pragmatic trial;  Metabolic syndrome;  Drug discontinuation  ATP, Adult Treatment Panel III;  CATIE, Clinical Antipsychotic Trials of Intervention Effectiveness;  CUtLASS, Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia;  EPS, Extrapyramidal symptoms;  EUFEST, European First Episode Schizophrenia Trial;  FGAs, First-generation antipsychotics;  GAF, Global Assessment of Functioning;  GiSAS, Italian Group for the Study of Second-generation Antipsychotics;  ITT, Intention to treat;  LUNSERS, Liverpool University Neuroleptic Side Effect Rating Scale;  SGAs, Second-generation antipsychotics <img hspace="2" height="164" border="0" align="middle" width="217" vspace="2" alt="Full-size image (50K)" title="Full-size image (50K)" src="http://ars.els-cdn.com/content/image/1-s2.0-S155171441100098X-gr1.sml" data-thumbsrc="http://ars.els-cdn.com/content/image/1-s2.0-S155171441100098X-gr1.sml" data-fullsrc="http://ars.els-cdn.com/content/image/1-s2.0-S155171441100098X-gr1.jpg"> Fig. 1. The study drug discontinuation module in the trial monitoring form. Table 1. Examples of independently funded pragmatic RCT on long-term effectiveness of antipsychotic therapy in schizophrenia. Trial Registration. ClinicalTrials.gov Identifier NCT01052389. Corresponding author. Tel.: + 39 02 39014602; fax: + 39 39014300. EXECUTIVE COMMITTEE: Angelo Barbato (Principal Investigator), Barbara D'Avanzo (Trial Coordinator), Alberto Parabiaghi (Project Director), Mauro Tettamanti (Trial Statistician). STEERING COMMITTEE: Clive E. Adams, Eugenio Aguglia, Mariano Bassi, Giancarlo Breviario, Massimo Casacchia, Antonio Colotto, Arcadio Erlicher, Luigi Ferrannini, Farida Ferrato, Bruno Gentile, Maurizio Marcenaro, Antonino Mastroeni, Massimo C. Mauri, Mauro Percudani, Vincenzo Scalfari, Giovanni Smerieri, Marco Vaggi. STUDY TEAM: Grazia Buratti (Monitor), Lucia Buratti (Monitor), Andrea De Micheli, Karin Furlato, Simona D'Onofrio, Ilaria Mariannantoni, Filippo Rapisarda (Trial Manager), Francesca Riccardi, Alessandra Ruberto, Irene Ruggirello, Ilaria Santini, Federica Trivelli, Angelida Ullo. STUDY INVESTIGATORS: Germana Agnetti, Stefano Bignotti, Chiara Bufalino, Dario Cannavò, Carlo I. Cattaneo, Laura Comino, Angela D'Aloise, Ilaria F. De Gaspari, Vincenzo Florio, Antonio Francomano, Vincenzo Fricchione Parise, Liliana Gandolfo, Emanuela Ghinaglia, Lucio Ghio, Christian Groppi, Aristotele Hadjichristos, Adelia Lucattini, Samuele Manfrinati, Werner Natta, Gaetano Pinto, Rocco Pollice, Paolo Pomero, Danilo Rigamonti, Bartolomeo Senette. Copyright 2011 Elsevier Inc. All rights reserved.

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