NCT03510325

Sequential Multiple-Assignment Randomized Trials to Compare Antipsychotic Treatments(SMART-CAT)

Sequential Multiple-Assignment Randomized Trials to Compare Antipsychotic Treatments

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 762 (actual)
• Sponsor: Shanghai Mental Health Center · Academic / Other
• Sex: All
• Age: 16 Years – 45 Years
• Healthy volunteers: Not accepted

Summary

This study is a sequential multiple-assignment randomized trial (RCT) of antipsychotic medication treatment in first-episode schizophrenia patients in the real-world settings.Through analysis of treatment efficacy rate and adverse reactions and pharmacoeconomic evaluation, this project intends to provide evidence for the selection of antipsychotics in FES patients as well as the efficacy and safety of using clozapine in the early phase of schizophrenia treatment by comparing with other SGAs.

Detailed description

A total of 720 first-episode schizophrenia (FES) patients will be enrolled and followed up for 12 months in this study. The trial includes three treatment phases (each phase lasting for 8 weeks) and a naturalistic follow-up phase. Phase 1 is a 8-week randomized controlled trial; patients will be randomly assigned to one of the treatments with oral olanzapine, risperidone, amisulpride, aripiprazole or perphenazine. Patients who had an acceptable response to the randomly assigned drug therapy will remain on that treatment for a 12-month treatment period. Subjects who fail to respond in phase 1 will switch to phase 2, an equipoise-stratified randomization trial, in which patients will be randomly assigned to oral olanzapine, amisulpride or clozapine for another 8 weeks. No-responders in phase 2 will further enter an open label trial (phase 3). Patients who receive clozapine in phase 2 will be assigned to an extended clozapine treatment or modified electroconvulsive therapy add-on therapy (Phase 3A). Patients who were not assigned to clozapine in phase 2 will be assigned to treatment with clozapine or another SGAs not previously used in phase 1 and 2 (Phase 3B).

Conditions

• Schizophrenia

Interventions

Type	Name	Description
DRUG	Phase 1: Olanzapine	Initial dosage: 5-10 mg; recommended dosage: 5-20 mg/d; dosage form: po. duration: 8 weeks
DRUG	Phase 1: Risperidone	Initial dosage: 1-2 mg; recommended dosage: 2-6 mg/d; dosage form: po. duration: 8 weeks
DRUG	Phase 1: Amisulpride	Initial dosage: 200-400 mg; recommended dosage: 400-1200 mg/d; dosage form: po. duration: 8 weeks
DRUG	Phase 1: Aripiprazole	Initial dosage: 5-10 mg; recommended dosage: 10-30 mg/d; dosage form: po. duration: 8 weeks
DRUG	Phase 1: Perphenazine	Initial dosage: 2-4 mg; recommended dosage: 6-36 mg/d; dosage form: po. duration: 8 weeks
DRUG	Phase 2: Olanzapine	Initial dosage: 5-10 mg; recommended dosage: 5-20 mg/d; dosage form: po. duration: 8 weeks
DRUG	Phase 2: Amisulpride	Initial dosage: 200-400 mg; recommended dosage: 400-1200 mg/d; dosage form: po. duration: 8 weeks
DRUG	Phase 2: Clozapine	Initial dosage: 25-50 mg; recommended dosage: 200-400 mg/d; dosage form: po. duration: 8 weeks
OTHER	Phase 3A: Clozapine extended treatment or Combined clozapine-MECT therapy	Clozapine extended treatment: dosage: 200-600 mg/d; dosage form: po. Combined clozapine-MECT therapy: Dosage of clozapine: 200-600 mg/d; The modified electroconvulsive therapy (MECT) will be administered three times per week for the first 2 weeks, then twice a week for the next 2 weeks. The total treatment duration is about one month.
DRUG	Phase 3B: Clozapine or another SGAs	Clozapine: Initial dosage: 25-50 mg; recommended dosage: 200-600 mg/d; duration: 8 weeks Another Second generation antipsychotics (SGAs) (not previously used in phase 1 and 2): Olanzapine, risperidone, amisulpride, or aripiprazole The dosage of each drug is the same as that of phase 1 and phase 2.

Timeline

• Start date: 2019-02-12
• Primary completion: 2023-09-27
• Completion: 2023-09-27
• First posted: 2018-04-27
• Last updated: 2025-04-08

Locations

7 sites across 1 country: China