Sequential Multiple-Assignment Randomized Trials to Compare Antipsychotic Treatments(SMART-CAT)
- Conditions
- Schizophrenia
- Interventions
- Registration Number
- NCT03510325
- Lead Sponsor
- Shanghai Mental Health Center
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 762
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Paliperidone long-acting injection Paliperidone long-acting injection dosage form:im dosage:75-150mg frequency:once a month duration:If the drug is effective, it can be taken for a long time. If the drug is ineffective or the side effect is too difficult to tolerate, the drug should be changed according to the treatment stage. Olanzapine Olanzapine dosage form:po dosage:5-20mg frequency:qn duration:If the drug is effective, it can be taken for a long time. If the drug is ineffective or the side effect is too difficult to tolerate, the drug should be changed according to the treatment stage. Risperidone Risperidone dosage form:po dosage:4-6mg frequency:2 doses duration:If the drug is effective, it can be taken for a long time. If the drug is ineffective or the side effect is too difficult to tolerate, the drug should be changed according to the treatment stage. Amisulpride Aripiprazole dosage form:po dosage:0.4-1.2g frequency:2 doses duration:If the drug is effective, it can be taken for a long time. If the drug is ineffective or the side effect is too difficult to tolerate, the drug should be changed according to the treatment stage. Aripiprazole Amisulpride dosage form:po dosage:15-30mg frequency:qd duration:If the drug is effective, it can be taken for a long time. If the drug is ineffective or the side effect is too difficult to tolerate, the drug should be changed according to the treatment stage.
- Primary Outcome Measures
Name Time Method Treatment efficacy rate 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 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 Outcome Measures
Name Time Method Change from baseline in cognitive function: MCCB baseline,2 months,4 months and 6 months and 12 months MATRICS consensus cognitive battery (MCCB) consists of 10 tests that assess cognitive performance in 7 domains, including processing speed, attention/vigilance, working memory, verbal memory, visual learning, reasoning and problem solving, and social cognition.
Change from baseline in cognitive function: NBSC baseline,2 months,4 months and 6 months and 12 months New cognitive battery for patients with schizophrenia in China(NBSC). NBSC includes 4 tests from MCCB and 5 new tests (Trial making A, BACS, HVLT-R learning and recall, CPTIP, dominant hand Grooved Pegboard, Color Trails I and II, PASAT)
Safety index: Blood pressure baseline,2 months,4 months and 6 months and 12 months Blood pressure in mmHg
Safety index: Heart rate baseline,2 months,4 months and 6 months and 12 months Heart rate
Safety index: Respiratory rate baseline,2 months,4 months and 6 months and 12 months respiratory rate
Safety index: Vital signs baseline,2 months,4 months and 6 months and 12 months body temperature in celsius
Safety index: Blood count baseline,2 months,4 months and 6 months and 12 months Blood count
Safety index: Liver function baseline,2 months,4 months and 6 months and 12 months \*Concentration of ALT, AST, GGT, ALP, TB, and DB.
Safety index: renal function baseline,2 months,4 months and 6 months and 12 months \*Concentration of serum creatinine, blood urea nitrogen, uric acid, serum cystatin C, homocysteine.
Safety index: thyroid function baseline,2 months,4 months and 6 months and 12 months Thyroid function related hormone levels will be tested, including FT3, FT4, T3, TSH, and T4.
Safety index: prolactin baseline,2 months,4 months and 6 months and 12 months Serum prolactin level
Safety index: QTc interval baseline,2 months,4 months and 6 months and 12 months QTc interval
Metabolic side effects: body weight baseline,2 months,4 months and 6 months and 12 months Weight in kilograms
Metabolic side effects: BMI baseline,2 months,4 months and 6 months and 12 months BMI in kg/m\^2
Metabolic side effects: waist circumstance baseline,2 months,4 months and 6 months and 12 months Waist circumstance in centimeter
Metabolic side effects: fasting blood-glucose baseline,2 months,4 months and 6 months and 12 months Fasting blood-glucose
Metabolic side effects: insulin index baseline,2 months,4 months and 6 months and 12 months Insulin resistance was assessed using homeostasis model assessment (HOMA-IR).
Metabolic side effects: serum lipid level baseline,2 months,4 months and 6 months and 12 months Concentration of serum triglyceride, LDL-C(low density lipoprotein cholesterol), HDL-C(high density lipoprotein cholesterol) and apolipoprotein.
Metabolic side effects: Visual Analogue Scale (VAS) baseline,2 months,4 months and 6 months and 12 months Visual Analogue Scale (VAS) was used to evaluate the desire to eat, hunger sensation and willingness to eat. The scale consists of 3 items, each scored from 0 to 10. The higher scores mean a stronger desire to eat, hunger sensation and willingness to eat.
Metabolic side effects: Physical Activity Evaluation baseline,2 months,4 months and 6 months and 12 months Physical Activity Evaluation
MRI examinaitons baseline,2 months and 4 months Change of grey matter volume and functional connectivity in certain brain region was focused in the MRI examinations, to evaluate the ability of MRI examinaitons (structural MRI, functional MRI and Magnetic Resonance Spectroscopy) to predict response to antipsychotic treatment in first-episode schizophrenia.
Pharmacogenomics baseline,2 months,4 months \*Blood sample was collected and genes related to drug efficacy and adverse reaction were tested to evaluate the ability of pharmacogenomics to predict response to antipsychotic treatment in first-episode schizophrenia.
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 Clinician-Rated Dimensions of Psychosis Symptom severity (CRDPS). The CRDPS scale evaluates eight symptom dimensions of psychosis. Each symptom domain is rated for the past 7 days on a 5-point scale ranging from 0 (absent) to 4 (present and severe).
Cost inventory baseline,2 months,4 months, 6 months and 12 months Direct medical costs (for example, antipsychotics costs, medical examinations costs, health care and service costs and adverse events costs) and indirect costs (such as traffic, nursing, and losing of labor) of the treatments.
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 Clinical Global Impression Scale-Severity (CGI-S), including assessment of disease severity and overall efficacy. The severity of the disease was scored on an eight-point scale ranging from 0 (not rated) to 7 (extremely severe). The overall efficacy was assessed on an 8-point scale ranging from 0 (not assessed) to 7 (significant deterioration).
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 The Calgary Depression Scale for Schizophrenia (CDSS) consists of nine items, each scored from 0 to 3. A total score greater than 6 is considered depression.
Social function baseline,2 months,4 months and 6 months and 12 months Chinese version of UPSA-B, the UCSD (University of California,San Diego) Performance-based Skills Assessment-Brief, consists of two parts: financial skill (A and B) and communication skill. The score of financial skill A range from 0 to 5. The score of financial skill B range from 0 to 6. The score of communication skill range from 0 to 9. The higher scores mean a better outcome.
Life quality: The Heinirich Quality of life Scale (HRQOL) baseline,2 months,4 months and 6 months and 12 months The Heinirich Quality of life Scale (HRQOL) consists of 21 items, each scored from 0 to 6. The higher scores mean a better outcome.
Life quality: Medication Satisfaction Questionnaire (MSN) baseline,2 months,4 months and 6 months and 12 months Medication Satisfaction Questionnaire (MSN) has one item, scored from 1 to 7. The higher scores indicate higher satisfaction with the medication.
Life quality: Subjective Well-being under Neuroleptics (SWN) baseline,2 months,4 months and 6 months and 12 months Subjective Well-being under Neuroleptics (SWN) consists of 20 items, each scored from 1-6.
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 The Barnes Akathisia Scale (BAS) will be used to evaluate objective performance and subjective experience of akathisia, scored from 0 to 3, and the overall clinical evaluation of akathisia is scored from 0 to 5. The higher scores mean a more serious side effect.
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 Simpson-Angus Extrapyramidal Side Effects Scale (SAS) consists of 10 items, each scored from 0 to 4. The higher scores mean a more serious side effect.
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 Abnormal Involuntary Movement Scale (AIMS) consists of 12 items. The first 10 of 12 items is scored from 0 to 4, and the last 2 is scored from 0 to 1. The higher scores mean the more obvious abnormal involuntary movement.
Sexual dysfunction baseline,0.5 months,1 months, 2 months,4 months , 6 months , 8 months and 12 months Arizona Sexual Experiences Scale (ASEX) includes 5 items, each scored from 1-6. A total score greater than or equal to 19 and any item greater than or equal to 5, or any 3 items greater than or equal to 4, can help clinical diagnosis of sexual dysfunction.
Metabolic side effects: assessment of feeding behavior baseline,2 months,4 months and 6 months and 12 months Three-Factor Eating Questionnaire (TFEQ-21) consists of 21 items, including 3 dimensions (non-controlled eating, cognitively restricted eating, and emotional eating). Each item is scored from 1 to 4, and the first 16 item requires reverse scoring before calculating dimension scores. The higher scores mean a higher tendency for non-controlled eating, cognitively restricted eating, and emotional eating.
Lipidomics baseline,2 months,4 months \*Serum sample was collected for lipidomic analysis to investigate correlation between serum lipids and rapid weight gain in first-episode schizophrenia.
Trial Locations
- Locations (7)
Beijing Anding Hospital of Capital Medical University
🇨🇳Beijing, Beijing, China
Renmin Hospital of Wuhan University
🇨🇳Wuhan, Hubei, China
Nanjing Brain Hospital Affiliated to Nanjing Medical University
🇨🇳Nanjing, Jiangsu, China
Dalian Seventh People's Hospital
🇨🇳Dalian, Liaoning, China
First Affiliated Hospital of Kunming Medical University
🇨🇳Kunming, Yunnan, China
Hangzhou Seventh People's Hospital
🇨🇳Hangzhou, Zhejiang, China
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine
🇨🇳Shanghai, Shanghai, China