Randomized Evaluation of the Effectiveness of Clozapine and Aripiprazole Versus Clozapine and Haloperidol in the Treatment of Schizophrenia (CHAT)

Randomized Evaluation of the Effectiveness of Clozapine and Aripiprazole Versus Clozapine and Haloperidol in the Treatment of Schizophrenia

Randomized Evaluation of the Effectiveness of Clozapine and Aripiprazole Versus Clozapine and Haloperidol in the Treatment of Schizophrenia. An Independent, Pragmatic, Multicentre, Parallel-Group, Superiority Trial.

The principal clinical question to be answered by CHAT (Clozapine Haloperidol Aripiprazole Trial) is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared to combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time.

Inclusion Criteria: Current treatment with clozapine for the primary indication of schizophrenia (clinical diagnosis, guided by DSM-IV criteria). Treatment with clozapine for at least six months at a stable dose of 400 mg or more per day, unless the size of the dose was limited by side-effects. Unsatisfactory benefit from clozapine treatment, as indicated by the presence of positive symptoms (delusions, hallucinations, abnormal behaviour, clinical diagnosis) Age 18 and above. Agreement between investigator and patient to enter the study. The patient is normally resident in Italy. It is considered clinically reasonable to try combination treatment with clozapine and aripiprazole or with clozapine and haloperidol. Uncertainty about which trial treatment would be best for the participant. No medical disorder or condition contraindicates either of the investigational drugs. Agreement between investigator and patient to discontinue any antipsychotic drugs other than clozapine (including long-acting antipsychotic drugs).

Cipriani A, Accordini S, Nose M, Purgato M, Girlanda F, Tansella M, Barbui C. Aripiprazole versus haloperidol in combination with clozapine for treatment-resistant schizophrenia: a 12-month, randomized, naturalistic trial. J Clin Psychopharmacol. 2013 Aug;33(4):533-7. doi: 10.1097/JCP.0b013e318296884f.

Barbui C, Accordini S, Nose M, Stroup S, Purgato M, Girlanda F, Esposito E, Veronese A, Tansella M, Cipriani A; CHAT (Clozapine Haloperidol Aripiprazole Trial) Study Group. Aripiprazole versus haloperidol in combination with clozapine for treatment-resistant schizophrenia in routine clinical care: a randomized, controlled trial. J Clin Psychopharmacol. 2011 Jun;31(3):266-73. doi: 10.1097/JCP.0b013e318219cba3.

Nose M, Accordini S, Artioli P, Barale F, Barbui C, Beneduce R, Berardi D, Bertolazzi G, Biancosino B, Bisogno A, Bivi R, Bogetto F, Boso M, Bozzani A, Bucolo P, Casale M, Cascone L, Ciammella L, Cicolini A, Cipresso G, Cipriani A, Colombo P, Dal Santo B, De Francesco M, Di Lorenzo G, Di Munzio W, Ducci G, Erlicher A, Esposito E, Ferrannini L, Ferrato F, Ferro A, Fragomeno N, Parise VF, Frova M, Gardellin F, Garzotto N, Giambartolomei A, Giupponi G, Grassi L, Grazian N, Grecu L, Guerrini G, Laddomada F, Lazzarin E, Lintas C, Malchiodi F, Malvini L, Marchiaro L, Marsilio A, Mauri MC, Mautone A, Menchetti M, Migliorini G, Mollica M, Moretti D, Mule S, Nicholau S, Nose F, Occhionero G, Pacilli AM, Pecchioli S, Percudani M, Piantato E, Piazza C, Pontarollo F, Pycha R, Quartesan R, Rillosi L, Risso F, Rizzo R, Rocca P, Roma S, Rossattini M, Rossi G, Rossi G, Sala A, Santilli C, Sarao G, Sarnicola A, Sartore F, Scarone S, Sciarma T, Siracusano A, Strizzolo S, Tansella M, Targa G, Tasser A, Tomasi R, Travaglini R, Veronese A, Ziero S. Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia. Trials. 2009 May 15;10:31. doi: 10.1186/1745-6215-10-31.