Preventing Relapse in Schizophrenia: Oral Antipsychotics Compared To Injectables: Evaluating Efficacy

Study Overview
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Brief Summary
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This study is designed to find out whether taking antipsychotic medication once every two weeks by injection compared to taking daily oral medication will help people with schizophrenia maintain better control of their symptoms.

Detailed Description
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As is the case with many chronic illnesses, it can be challenging for people with schizophrenia to take multiple pills every day on a long-term basis. At the same time, missing or discontinuing the anti-psychotic medications that treat schizophrenia substantially increases the risk of relapse and re-hospitalization. This study will determine how effective long-acting injectable risperidone is compared to oral antipsychotic medications to help patients who have schizophrenia. Patients who enroll in the study will be randomly assigned to receive either long-acting injectable risperidone or to receive oral atypical antipsychotic medication. The atypical antipsychotics that are included for patients in the oral group are: aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone. Patients in the oral group will receive whichever of the five atypical antipsychotic medications they and their study doctor decide is best for them. Patients in the oral group will be allowed to switch to others of the five medications during the study if they and their doctor think that is best. Patients in this study will be evaluated at the beginning of the study and then again every two weeks for up to 30 months (2 1/2 years). Each two-week visit will take about 20 minutes. At the visit, patients will receive medication and will be examined for side effects of the medications, their vital signs (heart rate, blood pressure, weight, and waist measurement) will be measured, and they will be asked a few questions about attendance at visits and taking medication. The visit that occurs every three months will take about one hour, instead of 20 minutes, and will include additional questions, an examination for muscle stiffness or abnormal body movements, and an interview from a member of the research team conducted using computer technology. In addition, blood and urine samples may be collected about seven times throughout the 30 months of the study treatment. Patients who enroll in this study after the halfway point of the study, may not receive a full 30 months of treatment, but it is planned that all patients will have the opportunity to receive no less than 18 months of treatment.

Official Title
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Preventing Relapse: Oral Antipsychotics Compared To Injectables: Evaluating Efficacy (PROACTIVE)

Conditions
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Schizophrenia, Schizoaffective Disorder

Intervention / Treatment
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* Drug: Risperidone microspheres
* Drug: Risperidone
* Drug: Olanzapine
* Drug: Quetiapine
* Drug: Ziprasidone
* Drug: Aripiprazole
* Drug: Paliperidone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All schizophrenia and schizoaffective patients whose clinicians are considering long-term treatment with an atypical (second generation) antipsychotic medication Worsening of illness (schizophrenia) within 12 months of study entry as defined by: hospitalization, increased level of clinical care, and/or present clinical Global Impressions Severity rating of moderate or worse Exclusion Criteria: First episode patients as defined by a patient who: has never received antipsychotic medication and has never been hospitalized for psychiatric illness; or, is receiving antipsychotic medication for the first time associated with a first diagnosis of schizophrenia. Pregnant or breastfeeding Patients with unstable medical conditions Patients with previous history of failure to respond to an adequate trial of clozapine Patients with a known allergy to risperidone or a previous history of failure to respond to an adequate trial of risperidone. However, patients with known allergies or failure to respond to any of the other medications (aripiprazole, olanzapine, quetiapine or ziprasidone) will not receive that medication if they are randomized to the oral medication arm, but are not excluded from the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Injectable<br>Participants assigned to receive long-acting injectable risperidone | Drug: Risperidone microspheres<br>* Minimum dose is 12.5 mg every 2 weeks. Maximum dose is 75 mg every 2 weeks.<br>* Other names: Risperdal Consta;|
| Active Comparator: Oral<br>Participants assigned to receive oral atypical antipsychotic medication | Drug: Risperidone<br>* Target dose is 4 mg/day.<br>* Other names: Risperdal;Drug: Olanzapine<br>* Target dose is 15 mg/day.<br>* Other names: Zyprexa;Drug: Quetiapine<br>* Target dose is 600 mg/day.<br>* Other names: Seroquel;Drug: Ziprasidone<br>* Target dose is 120 mg/day.<br>* Other names: Geodon;Drug: Aripiprazole<br>* Target dose is 20 mg/day.<br>* Other names: Abilify;Drug: Paliperidone<br>* Target dose is 6 mg/day.<br>* Other names: Invega;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Substantial Clinical Deterioration Measured by Psychotic Symptoms | Brief Psychiatric Rating Scale (BPRS) psychosis cluster. Score range is based on the score range for individual items rather than the factor total because is factors have different numbers of items. Score range is 1 -7 where 1 + no symptomatology and 7 = very severe symptoms. | Measured throughout study up to 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Discontinuing From the Study |  | Measured throughout study up to 30 months | 
| Number of Days in Hospital |  | Measured throughout study up to 30 months | 
| Control of Psychiatric Symptoms | Brief Psychiatric Rating Scale (BPRS) total score | Measured throughout study up to 30 months | 
| Quality of Life Measures | Scale of Functioning (SOF) | Measured throughout study up to 30 months | 
| Side Effects and Metabolic Measures | The highest severity of each of 24 adverse event (AE) that was assessed.over the 30 month study period. The mean severity on a scale of 1 (none) to 4 very severe symptom was recorded at each biweekly visit. Results for each variable are summarized over time so that each subject has a single mean severity rating for each AE. There is no named scale. Each of the side effects measured is named in ways that are clear to medical readers e.g anorexia. The range is 1 none to 4 very severe. Therefore, a higher scale score is worse. | Measured throughout study up to 30 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapse, Prevention, Schizophrenia, Injectable Medication