Clinical trial NCT03510325: Sequential Multiple-Assignment Randomized Trials to Compare Antipsychotic Treatments(SMART-CAT)
Official title: Sequential Multiple-Assignment Randomized Trials to Compare Antipsychotic Treatments
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Keywords: Schizophrenia;
Antipsychotics；
first-episode;
switch
Lead sponsor: Shanghai Mental Health Center
Sponsor class: OTHER
First posted: 2018-04-27
Enrollment: 762
Sex: ALL
Minimum age (years): 16
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

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).

Eligibility criteria: Inclusion criteria:

1. 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.
2. Inpatients or outpatients.
3. 16-45 years of age.
4. First episode, and the course no more than 3 years.
5. 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.
6. 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.
7. Patients must demonstrate adequate decisional capacity to make a choice about participating in this research study and must provide informed consent to participate.

Exclusion criteria:

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

Primary outcomes:
measure: Treatment efficacy rate
timeFrame: baseline,0.5 months,1 months, 2 months,4 months , 6 months , 8 months and 12 months
measure: All-cause dropout rate
timeFrame: baseline,0.5 months,1 months, 2 months,4 months , 6 months , 8 months and 12 months
Secondary outcomes:
measure: Change from baseline in Clinician-Rated Dimensions of Psychosis Symptom severity (CRDPS)
timeFrame: baseline,0.5 months,1 months, 2 months,4 months , 6 months , 8 months and 12 months
measure: Cost inventory
timeFrame: baseline,2 months,4 months, 6 months and 12 months
measure: Change from baseline in Clinical Global Impression Scale-Severity (CGI-S)
timeFrame: baseline,0.5 months,1 months, 2 months,4 months , 6 months , 8 months and 12 months
measure: Change from baseline in Calgary Depression Scale for Schizophrenia (CDSS)
timeFrame: baseline,0.5 months,1 months, 2 months,4 months , 6 months , 8 months and 12 months
measure: Social function
timeFrame: baseline,2 months,4 months and 6 months and 12 months
measure: Life quality: The Heinirich Quality of life Scale (HRQOL)
timeFrame: baseline,2 months,4 months and 6 months and 12 months
measure: Life quality: Medication Satisfaction Questionnaire (MSN)
timeFrame: baseline,2 months,4 months and 6 months and 12 months
measure: Life quality: Subjective Well-being under Neuroleptics (SWN)
timeFrame: baseline,2 months,4 months and 6 months and 12 months
measure: Extrapyramidal adverse effects: The Barnes Akathisia Scale (BAS)
timeFrame: baseline,0.5 months,1 months, 2 months,4 months , 6 months , 8 months and 12 months
measure: Extrapyramidal adverse effects: Simpson-Angus Extrapyramidal Side Effects Scale (SAS)
timeFrame: baseline,0.5 months,1 months, 2 months,4 months , 6 months , 8 months and 12 months
measure: Extrapyramidal adverse effects: Abnormal Involuntary Movement Scale (AIMS)
timeFrame: baseline,0.5 months,1 months, 2 months,4 months , 6 months , 8 months and 12 months
measure: Sexual dysfunction
timeFrame: baseline,0.5 months,1 months, 2 months,4 months , 6 months , 8 months and 12 months
measure: Change from baseline in cognitive function: MCCB
timeFrame: baseline,2 months,4 months and 6 months and 12 months
measure: Change from baseline in cognitive function: NBSC
timeFrame: baseline,2 months,4 months and 6 months and 12 months
measure: Safety index: Blood pressure
timeFrame: baseline,2 months,4 months and 6 months and 12 months
measure: Safety index: Heart rate
timeFrame: baseline,2 months,4 months and 6 months and 12 months
measure: Safety index: Respiratory rate
timeFrame: baseline,2 months,4 months and 6 months and 12 months
measure: Safety index: Vital signs
timeFrame: baseline,2 months,4 months and 6 months and 12 months
measure: Safety index: Blood count
timeFrame: baseline,2 months,4 months and 6 months and 12 months
measure: Safety index: Liver function
timeFrame: baseline,2 months,4 months and 6 months and 12 months
measure: Safety index: renal function
timeFrame: baseline,2 months,4 months and 6 months and 12 months
measure: Safety index: thyroid function
timeFrame: baseline,2 months,4 months and 6 months and 12 months
measure: Safety index: prolactin
timeFrame: baseline,2 months,4 months and 6 months and 12 months
measure: Safety index: QTc interval
timeFrame: baseline,2 months,4 months and 6 months and 12 months
measure: Metabolic side effects: body weight
timeFrame: baseline,2 months,4 months and 6 months and 12 months
measure: Metabolic side effects: BMI
timeFrame: baseline,2 months,4 months and 6 months and 12 months
measure: Metabolic side effects: waist circumstance
timeFrame: baseline,2 months,4 months and 6 months and 12 months
measure: Metabolic side effects: fasting blood-glucose
timeFrame: baseline,2 months,4 months and 6 months and 12 months
measure: Metabolic side effects: insulin index
timeFrame: baseline,2 months,4 months and 6 months and 12 months
measure: Metabolic side effects: serum lipid level
timeFrame: baseline,2 months,4 months and 6 months and 12 months
measure: Metabolic side effects: assessment of feeding behavior
timeFrame: baseline,2 months,4 months and 6 months and 12 months
measure: Metabolic side effects: Visual Analogue Scale (VAS)
timeFrame: baseline,2 months,4 months and 6 months and 12 months
measure: Metabolic side effects: Physical Activity Evaluation
timeFrame: baseline,2 months,4 months and 6 months and 12 months
measure: MRI examinaitons
timeFrame: baseline,2 months and 4 months
measure: Pharmacogenomics
timeFrame: baseline,2 months,4 months
measure: Lipidomics
timeFrame: baseline,2 months,4 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Anding Hospital of Capital Medical University
state: Beijing
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
state: Hubei
city: Nanjing
country: China
facility: Nanjing Brain Hospital Affiliated to Nanjing Medical University
state: Jiangsu
city: Dalian
country: China
facility: Dalian Seventh People's Hospital
state: Liaoning
city: Shanghai
country: China
facility: Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Kunming
country: China
facility: First Affiliated Hospital of Kunming Medical University
state: Yunnan
city: Hangzhou
country: China
facility: Hangzhou Seventh People's Hospital
state: Zhejiang
Study officials:
References:
citation: 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.