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

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

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Any FDA approved antipsychotic agent; Drug: aripiprazole long acting injectable formulation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 489
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85713
      • La Frontera
  • California
    • Granada Hills, California, United States, 91344
      • San Fernando Mental Health Center
    • Palo Alto, California, United States, 94304
      • Stanford School of Medicine
  • Florida
    • Fort Lauderdale, Florida, United States, 33319
      • Henderson Behavioral Health
    • Gainesville, Florida, United States, 32614
      • Meridian Behavioral Healthcare
    • Jacksonville, Florida, United States, 32209
      • U. of Florida College of Medicine
    • Leesburg, Florida, United States, 34749
      • Lifestream Behavioral Center
    • Saint Petersburg, Florida, United States, 33711
      • Suncoast Center
    • Tallahassee, Florida, United States, 32308
      • Apalachee Center, Inc.
    • West Palm Beach, Florida, United States, 33407
      • Jerome Golden Center for Behavioral Health
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Grady Memorial Hospital
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Feinberg School of Medicine
    • Granite City, Illinois, United States, 62040
      • Chestnut Health Systems
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Psychiatry Research
  • Massachusetts
    • Fall River, Massachusetts, United States, 02720
      • Corrigan Mental Health Center
    • Worcester, Massachusetts, United States, 01605
      • U. Mass Medical School
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • East Lansing, Michigan, United States, 48823
      • Early Treatment and Cognitive Health
    • Grand Rapids, Michigan, United States, 49503
      • Cherry Street Health Services
    • Kalamazoo, Michigan, United States, 49048
      • WMU School of Medicine
    • Mount Pleasant, Michigan, United States, 48858
      • Community Mental Health for Central Michigan
    • Muskegon, Michigan, United States, 49433
      • Muskegon County Community Mental Health
  • Missouri
    • Saint Louis, Missouri, United States, 63128
      • PsychCare Consultants Research
    • Saint Louis, Missouri, United States, 63104
      • Saint Louis University CRU
  • Nebraska
    • Omaha, Nebraska, United States, 68131
      • Creighton University
  • New Hampshire
    • Manchester, New Hampshire, United States, 03101
      • The Mental Health Center of Greater Manchester
    • Nashua, New Hampshire, United States, 03060
      • Healthy Perspectives
  • New Jersey
    • Paramus, New Jersey, United States, 07652
      • New Bridge Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27704
      • Carolina Behavioral Care
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Central Community Health Board of Hamilton Co.
    • Wooster, Ohio, United States, 44691
      • The Counseling Center of Wayne and Holmes Counties
  • Oregon
    • Eugene, Oregon, United States, 97401
      • PeaceHealth Medical Group
  • Tennessee
    • Huntingdon, Tennessee, United States, 38344
      • Carey Counseling Center
  • Texas
    • Beaumont, Texas, United States, 77701
      • Spindletop Center
    • Houston, Texas, United States, 77054
      • Baylor College of Medicine
    • Longview, Texas, United States, 75601
      • MHC Community Healthcore
    • San Antonio, Texas, United States, 78201
      • The Center for Health Care Services
  • Utah
    • Salt Lake City, Utah, United States, 84105
      • Psychiatric & Behavioral Solutions

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

1. First episode subjects: < 1 year of lifetime exposure to antipsychotic medication and only one episode of psychosis
2. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Clinician's Choice; 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; Investigators are free to choose the most appropriate treatment for their clients
Experimental: Aripiprazole Once Monthly; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Vanguard Research Group
• Collaborators: Otsuka America Pharmaceutical
• Investigators: Principal Investigator: John M Kane, M.D., Northwell Health

Publications and helpful links

General Publications

• Kane JM, Schooler NR, Marcy P, Correll CU, Achtyes ED, Gibbons RD, Robinson DG. Effect of Long-Acting Injectable Antipsychotics vs Usual Care on Time to First Hospitalization in Early-Phase Schizophrenia: A Randomized Clinical Trial. JAMA Psychiatry. 2020 Dec 1;77(12):1217-1224. doi: 10.1001/jamapsychiatry.2020.2076. Erratum In: JAMA Psychiatry. 2020 Dec 1;77(12):1310.
• Kane JM, Schooler NR, Marcy P, Achtyes ED, Correll CU, Robinson DG. Patients With Early-Phase Schizophrenia Will Accept Treatment With Sustained-Release Medication (Long-Acting Injectable Antipsychotics): Results From the Recruitment Phase of the PRELAPSE Trial. J Clin Psychiatry. 2019 Apr 23;80(3):18m12546. doi: 10.4088/JCP.18m12546.

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2014
• Primary Completion (Actual): March 31, 2019
• Study Completion (Actual): March 31, 2019

Study Registration Dates

• First Submitted: February 2, 2015
• First Submitted That Met QC Criteria: February 4, 2015
• First Posted (Estimate): February 10, 2015

Study Record Updates

• Last Update Posted (Actual): December 2, 2020
• Last Update Submitted That Met QC Criteria: November 16, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: First episode or recent onset
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Antidepressive Agents; Dopamine Agonists; Dopamine Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Aripiprazole; Antipsychotic Agents
• Other Study ID Numbers: COL.AOM.2013.005