Sequential Multiple-Assignment Randomized Trials to Compare Antipsychotic Treatments
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Enrollment
- 762
- Locations
- 7
- Primary Endpoint
- Treatment efficacy rate
Study Overview
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).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Eligibility Criteria
- Ages
- 16 Years to 45 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
【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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: 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.
Intervention: Phase 3B: Clozapine or another SGAs (Drug)
Outcomes
Primary Outcomes
Treatment efficacy rate
Time Frame: 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
Time Frame: 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.
Secondary Outcomes
- 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: Blood count(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: thyroid 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)