Sequential Multiple-Assignment Randomized Trials to Compare Antipsychotic Treatments
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 762
- 试验地点
- 7
- 主要终点
- Treatment efficacy rate
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 16 Years 至 45 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •16-45 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 >
- •Patients must demonstrate adequate decisional capacity to make a choice about participating in this research study and must provide informed consent to participate.
排除标准
- •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.
研究组 & 干预措施
【Phase 1】 Olanzapine RCT
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.
干预措施: Phase 1: Olanzapine (Drug)
【Phase 1】 Risperidone RCT
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.
干预措施: Phase 1: Risperidone (Drug)
【Phase 1】 Amisulpride RCT
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.
干预措施: Phase 1: Amisulpride (Drug)
【Phase 1】 Aripiprazole RCT
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.
干预措施: Phase 1: Aripiprazole (Drug)
【Phase 1】 Perphenazine RCT
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.
干预措施: Phase 1: Perphenazine (Drug)
【Phase 2】 Olanzapine ESR
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.
干预措施: Phase 2: Olanzapine (Drug)
【Phase 2】 Amisulpride ESR
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.
干预措施: Phase 2: Amisulpride (Drug)
【Phase 2】 Clozapine ESR
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.
干预措施: Phase 2: Clozapine (Drug)
【Phase 3】 Clozapine extended treatment or MECT add-on therapy
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.
干预措施: Phase 3A: Clozapine extended treatment or Combined clozapine-MECT therapy (Other)
【Phase 3】 Clozapine or another SGAs (olanzapine, amisulpride, risperidone, or aripiprazole)
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.
干预措施: Phase 3B: Clozapine or another SGAs (Drug)
结局指标
主要结局
Treatment efficacy rate
时间窗: baseline,0.5 months,1 months, 2 months,4 months , 6 months , 8 months and 12 months
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).
All-cause dropout rate
时间窗: baseline,0.5 months,1 months, 2 months,4 months , 6 months , 8 months and 12 months
Marked by the treatment discontinuation for any reasons, including poor efficacy, intolerance of adverse reactions, poor compliance and other reasons.
次要结局
- Safety index: Blood count(baseline,2 months,4 months and 6 months and 12 months)
- Safety index: thyroid function(baseline,2 months,4 months and 6 months and 12 months)
- Change from baseline in cognitive function: MCCB(baseline,2 months,4 months and 6 months and 12 months)
- Change from baseline in cognitive function: NBSC(baseline,2 months,4 months and 6 months and 12 months)
- Safety index: Blood pressure(baseline,2 months,4 months and 6 months and 12 months)
- Safety index: Heart rate(baseline,2 months,4 months and 6 months and 12 months)
- Safety index: Respiratory rate(baseline,2 months,4 months and 6 months and 12 months)
- Safety index: Vital signs(baseline,2 months,4 months and 6 months and 12 months)
- Safety index: Liver function(baseline,2 months,4 months and 6 months and 12 months)
- Safety index: renal function(baseline,2 months,4 months and 6 months and 12 months)
- Safety index: prolactin(baseline,2 months,4 months and 6 months and 12 months)
- Safety index: QTc interval(baseline,2 months,4 months and 6 months and 12 months)
- Metabolic side effects: body weight(baseline,2 months,4 months and 6 months and 12 months)
- Metabolic side effects: BMI(baseline,2 months,4 months and 6 months and 12 months)
- Metabolic side effects: waist circumstance(baseline,2 months,4 months and 6 months and 12 months)
- Metabolic side effects: fasting blood-glucose(baseline,2 months,4 months and 6 months and 12 months)
- Metabolic side effects: insulin index(baseline,2 months,4 months and 6 months and 12 months)
- Metabolic side effects: serum lipid level(baseline,2 months,4 months and 6 months and 12 months)
- Metabolic side effects: Visual Analogue Scale (VAS)(baseline,2 months,4 months and 6 months and 12 months)
- Metabolic side effects: Physical Activity Evaluation(baseline,2 months,4 months and 6 months and 12 months)
- MRI examinaitons(baseline,2 months and 4 months)
- Pharmacogenomics(baseline,2 months,4 months)
- 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)
- Life quality: The Heinirich Quality of life Scale (HRQOL)(baseline,2 months,4 months and 6 months and 12 months)
- Life quality: Medication Satisfaction Questionnaire (MSN)(baseline,2 months,4 months and 6 months and 12 months)
- Life quality: Subjective Well-being under Neuroleptics (SWN)(baseline,2 months,4 months and 6 months and 12 months)
- Extrapyramidal adverse effects: The Barnes Akathisia Scale (BAS)(baseline,0.5 months,1 months, 2 months,4 months , 6 months , 8 months and 12 months)
- Extrapyramidal adverse effects: Simpson-Angus Extrapyramidal Side Effects Scale (SAS)(baseline,0.5 months,1 months, 2 months,4 months , 6 months , 8 months and 12 months)
- Extrapyramidal adverse effects: Abnormal Involuntary Movement Scale (AIMS)(baseline,0.5 months,1 months, 2 months,4 months , 6 months , 8 months and 12 months)
- Sexual dysfunction(baseline,0.5 months,1 months, 2 months,4 months , 6 months , 8 months and 12 months)
- Metabolic side effects: assessment of feeding behavior(baseline,2 months,4 months and 6 months and 12 months)
- Lipidomics(baseline,2 months,4 months)