Comparison of a Long-acting Injectable Antipsychotic vs Clinician's Choice Early in Treatment to Break the Cycle of Relapse in Early Phase Schizophrenics

Study Overview
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Brief Summary
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The goal of this project is to show that the best possible option for preventing relapses in patients suffering from first episode (<1 year of anti-psychotic medication) or early phase (< 5 years of lifetime exposure to anti-psychotic medication) schizophrenia is by enhancing medication adherence. The study is designed to answer the question of whether the use of long-acting injectable (LAI) antipsychotics early in the course of treatment can break the cycle of frequent relapse that affects so many patients with early phase schizophrenia. The participating research sites (not individual patients) will be randomly assigned to either medication prescribed by their treating physician (with no restrictions) or to a regimen that involves a monthly long acting injectable antipsychotic. The sites will be assigned on a one to one basis to either of the arms taking into account types of patient population and geographical area. Patients enrolled in the study will participate in regular assessments either over the phone or in person and be followed for a period of 2 years. The primary outcome measure is time to first hospitalization.

Detailed Description
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Approximately 40 U.S. sites will participate in the study in order to enroll approximately 500 patients over a year period. They will be recruited into two cohorts - the first episode cohort and the early phase (EP) cohort, with approximately 250 patients in each cohort. Enrollment of patients will be discontinued when the appropriate number for the target for each cohort is reached. After providing written informed consent, patients will be screened for general eligibility by the clinical team at the site. Basic demographic data will be collected to determine suitability for inclusion into the study. The site will complete an information interview comprising data regarding symptomology and history, but the diagnosis of schizophrenia will fall to a centralized, remote blinded rater to enable consistency for eligibility. Prescribers at sites in the clinician's choice arm can treat the patients in the manner most appropriate for that individual. Prescribers at sites in the Aripiprazole Once Monthly arm monthly will prescribe and administer the medication according to recommendations contained in the product labeling. For a period of 2 years all subjects will receive bimonthly calls inquiring about visits to emergency rooms and hospitalization. At 4 month intervals information on use of services, insurance status, work, school attendance, and other service use outcomes will be assessed.

Official Title
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A Cluster Randomized, Multi-center, Parallel-group, Rater-blind Study Comparing Treatment With Aripiprazole Once Monthly and Treatment as Usual on Effectiveness in First Episode and Early Phase Illness in Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Any FDA approved antipsychotic agent
* Drug: aripiprazole long acting injectable formulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are able to provide written informed consent Have a confirmed diagnosis of schizophrenia as defined by Diagnostic and Statistical Manual (DSM) 5 criteria using the SCID (Structured Clinical Interview for DSM disorders) Are between the ages of 18 and 35, inclusive Have the following history with antipsychotic medications First episode subjects: < 1 year of lifetime exposure to antipsychotic medication and only one episode of psychosis EP subjects: between 1 year and 5 years of lifetime exposure to antipsychotic medication or subjects with < 1 year of lifetime antipsychotic medication and more than one episode of psychosis. For LAI subjects: Must be willing to accept an injectable form of treatment Exclusion Criteria: Have a current primary DSM-5 diagnosis other than schizophrenia, including schizophreniform disorder, schizoaffective disorder, major depressive disorder, bipolar disorder, delirium, dementia, and amnestic or other cognitive disorders. For LAI sites only - have a known allergy or intolerance to aripiprazole, or a past negative response to aripiprazole that is not explained by nonadherence Be pregnant or lactating Have any unstable medical condition that, in the opinion of the investigator, would be detrimental to the subject or would confound the results of the study Subjects in the MRI subset only- presence of any metal implants, pacemakers, irremovable prosthetic devices, or other devices or situations that may preclude imaging

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 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: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Clinician's Choice<br>Prescribers are not limited in the choice of treatment they can administer to their clients to alleviate the symptoms of schizophrenia. Any FDA approved antipsychotic agent can be used. Clients in the study wil be followed for 2 years | Drug: Any FDA approved antipsychotic agent<br>* Investigators are free to choose the most appropriate treatment for their clients<br>|
| Experimental: Aripiprazole Once Monthly<br>Aripiprazole long acting injectable formulation, 400mg per dose is to be administered once monthly. Clients in the study will be followed for 2 years | Drug: aripiprazole long acting injectable formulation<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Hospitalization | Assessments are done using best available data and patient interviews | Hospitalizations assessed every 2 months from baseline to Month 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Number of Psychiatric Hospitalizations Per Treatment Arm | Assessments are completed using best available data and patient interviews | Measured every 2 months from baseline to month 24 | 
| Brief Psychotic Rating Scale (BPRS) Total Score | The Brief Psychotic Rating Scale is an 18 item scale where each item is rated 1-7, the minimum total score is 18 and the maximum total score is 126. Higher scores indicate more severe symptoms. | Measured at Month 12 and Month 24 | 
| Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Sum of Scores | Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a 12 item scale with a total score range of 0 to 321 with higher scores indicating better cognitive functioning | Measured at Month 12 and Month 24 | 
| Quality of Life (QLS) Total Score | Quality of Life (QLS) is a 21 item scale where each item is rated from 0 to 7, the minimum score is 0 and the maximum score is 126 with higher scores indicating better overall functioning. | Measured at Month 12 and Month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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First episode or recent onset