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

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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00330863

Acronym

PROACTIVE

Enrollment

357

Registered

2006-05-29

Start date

2006-05-31

Completion date

2011-01-31

Last updated

2018-07-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Schizoaffective Disorder, Schizophrenia

Keywords

Relapse, Prevention, Schizophrenia, Injectable Medication

Brief summary

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

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.

Interventions

DRUGRisperidone microspheres

Minimum dose is 12.5 mg every 2 weeks. Maximum dose is 75 mg every 2 weeks.

DRUGRisperidone

Target dose is 4 mg/day.

DRUGOlanzapine

Target dose is 15 mg/day.

DRUGQuetiapine

Target dose is 600 mg/day.

DRUGZiprasidone

Target dose is 120 mg/day.

DRUGAripiprazole

Target dose is 20 mg/day.

DRUGPaliperidone

Target dose is 6 mg/day.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Substantial Clinical Deterioration Measured by Psychotic Symptoms	Measured throughout study up to 30 months	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.

Secondary

Measure	Time frame	Description
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	Measured throughout study up to 30 months	Brief Psychiatric Rating Scale (BPRS) total score
Quality of Life Measures	Measured throughout study up to 30 months	Scale of Functioning (SOF)
Side Effects and Metabolic Measures	Measured throughout study up to 30 months	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.

Countries

United States

Participant flow

Pre-assignment details

357 individuals consented to participation. However, 52 were either ineligible, withdrew consent, or lost to followup. Therefore, 305 individuals were randomized.

Participants by arm

Arm	Count
Injectable Participants assigned to receive long-acting injectable risperidone Risperidone microspheres: Minimum dose is 12.5 mg every 2 weeks. Maximum dose is 75 mg every 2 weeks.	153
Oral Participants assigned to receive oral atypical antipsychotic medication Risperidone: Target dose is 4 mg/day. Olanzapine: Target dose is 15 mg/day. Quetiapine: Target dose is 600 mg/day. Ziprasidone: Target dose is 120 mg/day. Aripiprazole: Target dose is 20 mg/day. Paliperidone: Target dose is 6 mg/day.	152
Total	305

Baseline characteristics

Characteristic	Injectable	Oral	Total
Age, Continuous	38.18 years STANDARD_DEVIATION 11.8	38.23 years STANDARD_DEVIATION 12.3	38.2 years STANDARD_DEVIATION 12.1
Clinical Global Impressions (CGI) Severity Scale	4.1 units on a scale STANDARD_DEVIATION 0.84	4.0 units on a scale STANDARD_DEVIATION 0.77	4.04 units on a scale STANDARD_DEVIATION 0.8
Race/Ethnicity, Customized African American	45 participants	40 participants	85 participants
Race/Ethnicity, Customized Caucasian	81 participants	78 participants	159 participants
Race/Ethnicity, Customized Hispanic	27 participants	31 participants	58 participants
Race/Ethnicity, Customized Other	0 participants	3 participants	3 participants
Region of Enrollment United States	153 participants	152 participants	305 participants
Sex: Female, Male Female	45 Participants	42 Participants	87 Participants
Sex: Female, Male Male	108 Participants	110 Participants	218 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	143 / 143	148 / 148
serious Total, serious adverse events	61 / 146	48 / 150

Outcome results

Primary

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.