Clozapine Versus Amisulpride in Treatment-resistant Schizophrenia Patients (ClozAmi)
Background: schizophrenia is a debilitating mental disorder affecting about 1% of the general population. About 30% of patients will not react to current drug treatment and defined as treatment-resistant schizophrenia patients (TRSP). The best studied therapeutic option for this population is clozapine therapy. Clozapine was shown to be effective than any other antipsychotic drug in TRSP. Moreover, augmentation of clozapine was not demonstrated to be more effective than clozapine monotherapy. Albeit Clozapine superiority in TRSP, its use may be involved with many adverse effects, some of them are life-threatening, and need for routine blood tests. Amisulpride is an atypical antipsychotic drug with a different mechanism of action than clozapine, with less adverse effects. No study compared directly amisulpride and clozapine in TRSP.
Study objective: to compare, for the first time, the broad clinical effectiveness of clozapine and amisulpride and their combination in TRSP.
Study Design: a clinical, prospective, naturalistic, randomized, comparative study simulating a real-world approach of clinical decision making.
Methods: a total of 140 TRSP will be recruited from a large regional mental health center. Participants will be randomized into two treatment groups (70 in each group): clozapine monotherapy and amisulpride monotherapy. Assessment will be done following 10 and 20 weeks of treatment. In case of treatment failure (insufficient clinical response or severe adverse effect) participants will be offered either to switch to clozapine treatment (for failed amisulpride treatment) or to augment clozapine with amisulpride (for failed clozapine monotherapy patients). Thereafter, participants will be followed-up for a year. Assessment will be made using clinician rated scales and self-completed questionnaires, rating the broad phenomenology of schizophrenia (psychosis, mood, anxiety, obsessive-compulsive, cognitive and quality of life) and drug-related adverse effects (objective and subjective).
Analysis: comparison of the effectiveness of the three treatment groups: amisulpride, clozapine and their combination, in the various dimensions of TRSP.
Treatment Resistant Disorders
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Clozapine Versus Amisulpride Versus Their Combination in the Treatment of Drug-resistant Schizophrenia Patients|
- Change from baseline in Positive and Negative Syndrome Scale (PANSS) [ Time Frame: 10, 20 weeks and endpoint ] [ Designated as safety issue: No ]
- Change from baseline in Clinical Global Impression - Severity (CGI-S) [ Time Frame: 10 , 20 weeks and endpoint ] [ Designated as safety issue: No ]
- Change from baseline in Beck Depression Inventory (BDI) [ Time Frame: 10 , 20 weeks and endpoint ] [ Designated as safety issue: No ]
- Change from baseline in Beck Anxiety Inventory (BAI) [ Time Frame: 10, 20 weeks and endpoint ] [ Designated as safety issue: No ]
- Change from baseline in Schizophrenia Quality of Life Scale (SQLS) [ Time Frame: 10, 20 weeks and endpoint ] [ Designated as safety issue: No ]
- Change from baseline in Simpson-Angus Scale (SAS) [ Time Frame: 5, 10, 15, 20 weeks, endpoint ] [ Designated as safety issue: Yes ]
- Change from baseline in Clozapine Adverse Effects Inventory (CAEI) [ Time Frame: 5, 10 ,15, 20 weeks, endpoint ] [ Designated as safety issue: Yes ]
|Study Start Date:||October 2011|
|Estimated Primary Completion Date:||October 2013 (Final data collection date for primary outcome measure)|
escalating dose of clozapine up to 900 mg/day
escalating dose of amisulpride up to 800 mg/day
Augmentation of clozapine with amisulpride
augmentation of clozapine with amisulpride
Please refer to this study by its ClinicalTrials.gov identifier: NCT01448499
|Contact: Amir Krivoy, M.D.||firstname.lastname@example.org|
|Geha Mental Health Center||Recruiting|
|Petach-Tikva, Israel, 49000|