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

NCT03510325 | Completed Phase 3 DMC

• 1 other identifier: CRC2017ZD03
• Study Type: interventional
• Target: 762
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

Schizophrenia

Keywords

Schizophrenia;; Antipsychotics；; first-episode;; switch

Outcome Measures

Primary Outcomes (2)

• Treatment efficacy rate

  A 40% reduction or more of the total score in the Positive and Negative Syndrome Scale (PANSS). The PANSS scale consists of 30 items, and each item is rated on a 7-point scale, ranging from 1 (no symptoms) to 7 (extremely severe).

  baseline,0.5 months,1 months, 2 months,4 months , 6 months , 8 months and 12 months

• All-cause dropout rate

  Marked by the treatment discontinuation for any reasons, including poor efficacy, intolerance of adverse reactions, poor compliance and other reasons.

  baseline,0.5 months,1 months, 2 months,4 months , 6 months , 8 months and 12 months

Secondary Outcomes (36)

• Change from baseline in Clinician-Rated Dimensions of Psychosis Symptom severity (CRDPS)

  baseline,0.5 months,1 months, 2 months,4 months , 6 months , 8 months and 12 months

• Cost inventory

  baseline,2 months,4 months, 6 months and 12 months

• Change from baseline in Clinical Global Impression Scale-Severity (CGI-S)

  baseline,0.5 months,1 months, 2 months,4 months , 6 months , 8 months and 12 months

• Change from baseline in Calgary Depression Scale for Schizophrenia (CDSS)

  baseline,0.5 months,1 months, 2 months,4 months , 6 months , 8 months and 12 months

• Social function

  baseline,2 months,4 months and 6 months and 12 months

Study Arms (10)

【Phase 1】 Olanzapine RCT

EXPERIMENTAL

Phase 1 of the trial is a 8-week randomized controlled trial (RCT); patients will be randomly assigned to one of five treatment arms with different oral antipsychotics, one of which is 'Olanzapine RCT'. Non-responders or patients with intolerable side effects in phase 1 will switch to phase 2.

Drug: Phase 1: Olanzapine

【Phase 1】 Risperidone RCT

EXPERIMENTAL

Phase 1 of the trial is a 8-week randomized controlled trial (RCT); patients will be randomly assigned to one of five treatment arms with different oral antipsychotics, one of which is 'Risperidone RCT'. Non-responders or patients with intolerable side effects in phase 1 will switch to phase 2.

Drug: Phase 1: Risperidone

【Phase 1】 Amisulpride RCT

EXPERIMENTAL

Phase 1 of the trial is a 8-week randomized controlled trial (RCT); patients will be randomly assigned to one of five treatment arms with different oral antipsychotics, one of which is 'Amisulpride RCT'. Non-responders or patients with intolerable side effects in phase 1 will switch to phase 2.

Drug: Phase 1: Amisulpride

【Phase 1】 Aripiprazole RCT

EXPERIMENTAL

Phase 1 of the trial is a 8-week randomized controlled trial (RCT); patients will be randomly assigned to one of five 8-week treatment arms with different oral antipsychotics, one of which is 'Aripiprazole RCT'. Non-responders or patients with intolerable side effects in phase 1 will switch to phase 2.

Drug: Phase 1: Aripiprazole

【Phase 1】 Perphenazine RCT

EXPERIMENTAL

Phase 1 of the trial is a 8-week randomized controlled trial (RCT); patients will be randomly assigned to one of five treatment arms with different oral antipsychotics, one of which is 'Perphenazine RCT'. Non-responders or patients with intolerable side effects in phase 1 will switch to phase 2.

Drug: Phase 1: Perphenazine

【Phase 2】 Olanzapine ESR

EXPERIMENTAL

Non-responders or patients with intolerable side effects in phase 1 will switch to phase 2, a 8-week equipoise-stratified randomization (ESR) trial; patients treated with risperidone, amisulpride, aripiprazole or perphenazine in phase 1 will be randomly assigned to one of three treatment arms, one of which is 'Olanzapine ESR'. Non-responders or patients with intolerable side effects in phase 2 will switch to phase 3.

Drug: Phase 2: Olanzapine

【Phase 2】 Amisulpride ESR

EXPERIMENTAL

Non-responders or patients with intolerable side effects in phase 1 will switch to phase 2, a 8-week equipoise-stratified randomization (ESR) trial; patients treated with olanzapine, risperidone, aripiprazole or perphenazine in phase 1 will be randomly assigned to one of three treatment arms, one of which is 'Amisulpride ESR'. Non-responders or patients with intolerable side effects in phase 2 will switch to phase 3.

Drug: Phase 2: Amisulpride

【Phase 2】 Clozapine ESR

EXPERIMENTAL

Non-responders or patients with intolerable side effects in phase 1 will switch to phase 2, a 8-week equipoise-stratified randomization (ESR) trial; patients in phase 1 will be randomly assigned to one of three treatment arms, one of which is 'Clozapine ESR'. Non-responders or patients with intolerable side effects in phase 2 will switch to phase 3.

Drug: Phase 2: Clozapine

【Phase 3】 Clozapine extended treatment or MECT add-on therapy

EXPERIMENTAL

If a patient received clozapine in phase 2 failed to response, the individual will be assigned to the clozapine extended treatment or modified electroconvulsive therapy (MECT) add-on therapy.

Other: Phase 3A: Clozapine extended treatment or Combined clozapine-MECT therapy

【Phase 3】 Clozapine or another SGAs (olanzapine, amisulpride, risperidone, or aripiprazole)

EXPERIMENTAL

Non-clozapine users in phase 2 will be assigned to clozapine or another Second generation antipsychotics (SGAs) not previously used in phase 1 and 2.

Drug: Phase 3B: Clozapine or another SGAs

Interventions

Phase 1: Olanzapine DRUG

Initial dosage: 5-10 mg; recommended dosage: 5-20 mg/d; dosage form: po. duration: 8 weeks

【Phase 1】 Olanzapine RCT

Phase 1: Risperidone DRUG

Initial dosage: 1-2 mg; recommended dosage: 2-6 mg/d; dosage form: po. duration: 8 weeks

【Phase 1】 Risperidone RCT

Phase 1: Amisulpride DRUG

Initial dosage: 200-400 mg; recommended dosage: 400-1200 mg/d; dosage form: po. duration: 8 weeks

【Phase 1】 Amisulpride RCT

Phase 1: Aripiprazole DRUG

Initial dosage: 5-10 mg; recommended dosage: 10-30 mg/d; dosage form: po. duration: 8 weeks

【Phase 1】 Aripiprazole RCT

Phase 1: Perphenazine DRUG

Initial dosage: 2-4 mg; recommended dosage: 6-36 mg/d; dosage form: po. duration: 8 weeks

【Phase 1】 Perphenazine RCT

Phase 2: Olanzapine DRUG

Initial dosage: 5-10 mg; recommended dosage: 5-20 mg/d; dosage form: po. duration: 8 weeks

【Phase 2】 Olanzapine ESR

Phase 2: Amisulpride DRUG

Initial dosage: 200-400 mg; recommended dosage: 400-1200 mg/d; dosage form: po. duration: 8 weeks

【Phase 2】 Amisulpride ESR

Phase 2: Clozapine DRUG

Initial dosage: 25-50 mg; recommended dosage: 200-400 mg/d; dosage form: po. duration: 8 weeks

【Phase 2】 Clozapine ESR

Phase 3A: Clozapine extended treatment or Combined clozapine-MECT therapy OTHER

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.

【Phase 3】 Clozapine extended treatment or MECT add-on therapy

Phase 3B: Clozapine or another SGAs DRUG

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.

【Phase 3】 Clozapine or another SGAs (olanzapine, amisulpride, risperidone, or aripiprazole)

Eligibility Criteria

• Age: 16 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must meet the DSM-5 diagnostic criteria for schizophrenia , schizophreniform disorder or schizoaffective disorder, based upon the structured clinical interview by research psychiatrist using Mini International Neuropsychiatric Interview 7.0 (M.I.N.I. 7.0), review of their clinical records, and input from available informants.
• Inpatients or outpatients.
• years of age.
• First episode, and the course no more than 3 years.
• Drug-naïve, or any antipsychotic medication had been used no more than 2 weeks, and the cumulative antipsychotic drug exposure time no more than 6 weeks in lifetime.
• The severity of psychotic symptoms is moderate or above, and the specific criteria including: have a score ≥4 on at least one item of Positive and Negative Syndrome Scale (PANSS) (delusions, conceptual disorganization, hallucinatory behavior, grandiosity, or suspiciousness/persecution), and PANSS total score \>70.
• Patients must demonstrate adequate decisional capacity to make a choice about participating in this research study and must provide informed consent to participate.

You may not qualify if:

• Patients were excluded if more than 3 years had passed since the onset of psychosis;
• They met any of the contraindications for any of the study drugs;
• Mental symptoms were caused by organic disease, severe physical illness, psychoactive substance dependence, mental retardation;
• They were pregnancy or breast-feeding; they were extreme agitation, stupor or negative suicide.

Sponsors & Collaborators

• Shanghai Mental Health Center: lead

Study Sites (7)

Beijing Anding Hospital of Capital Medical University

Beijing, Beijing Municipality, 100000, China

Location

Renmin Hospital of Wuhan University

Wuhan, Hubei, 430000, China

Location

Nanjing Brain Hospital Affiliated to Nanjing Medical University

Nanjing, Jiangsu, 210000, China

Location

Dalian Seventh People's Hospital

Dalian, Liaoning, 116000, China

Location

Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200030, China

Location

First Affiliated Hospital of Kunming Medical University

Kunming, Yunnan, 650000, China

Location

Hangzhou Seventh People's Hospital

Hangzhou, Zhejiang, 310000, China

Location

Related Publications (1)

• Li X, Guo X, Fan X, Feng T, Wang C, Yao Z, Xu X, Chen Z, Wang H, Xie S, He J, Zhuo K, Xiang Q, Cen H, Wang J, Smith RC, Jin H, Keshavan MS, Marder SR, Davis JM, Jiang K, Xu Y, Liu D. Sequential Multiple-Assignment Randomized Trials to Compare Antipsychotic Treatments (SMART-CAT) in first-episode schizophrenia patients: Rationale and trial design. Schizophr Res. 2021 Apr;230:87-94. doi: 10.1016/j.schres.2020.11.010. Epub 2020 Dec 2.

  PMID: 33279374 DERIVED

MeSH Terms

Conditions

Schizophrenia

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The sequential multiple assignment randomized trial design (SMART) design is based on the combination of sequential therapy and dynamic therapy, which is more suitable to assess the effectiveness of treatment options in the real world setting. Participants who had an acceptable response to the randomly assigned drug therapy will remain on that treatment for a 12-month treatment period, while non-responders will move to the next phase of the study to receive a new treatment.

Study Record Dates

• First Submitted: February 12, 2018
• First Posted: April 27, 2018
• Study Start: February 12, 2019
• Primary Completion: September 27, 2023
• Study Completion: September 27, 2023
• Last Updated: April 8, 2025

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (7)