Long-Acting Injectable Risperidone in the Treatment of Schizophrenia

Phase 3

Completed

• Conditions: Schizoaffective Disorder; Schizophrenia
• Interventions: Drug: IM risperidone; Drug: oral antipsychotic medication

• Registration Number: NCT00132314
• Lead Sponsor: US Department of Veterans Affairs

Brief Summary

In the proposed study 450 veterans with a primary diagnosis of schizophrenia who had at least one psychiatric hospitalization for schizophrenia in the previous 2 years would be randomly assigned at 16 VA medical centers to long-acting injectable risperidone or doctor's choice of oral antipsychotic medication (i.e., excluding other long-acting injectable medications, but not specifying any particular oral agents or dosages). Recruitment would take 27 months to complete, and the study would continue for a third year to allow 9 months of follow-up for the last patient recruited. All patients would be treated from the time of entry up to the end of the three-year study period. Follow-up assessments would continue quarterly. Treatments would not be blinded since giving placebo injections to the comparison group would interfere with the goal of comparing the acceptability of two different methods of medication administration. However, end points will be blindly rated.

Detailed Description

The purpose of the study is to assess the effectiveness of long-acting injectable risperidone on psychiatric inpatient hospitalization, schizophrenia symptoms, quality of life, medication adherence, side effects, and health care costs.

Objectives:

Primary: To evaluate the impact of long-acting intramuscular (IM) risperidone on risk of inpatient psychiatric hospitalization in comparison to standard oral antipsychotic treatment in a randomized controlled trial to be conducted with 450 veterans diagnosed with schizophrenia or schizoaffective disorder at 16 VA medical centers over three years.

Secondary: To evaluate adherence, health benefits, and costs of long-acting IM risperidone as compared to standard oral antipsychotic treatment as measured by: a) symptom reduction over 12 months, b) time to all-cause medication discontinuation, c) quality of life, d) VA and non-VA health service use and related costs, e) medication side effects, f) violent behavior, g) use of concomitant medication, and h) the incremental cost-effectiveness ratio.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2005-08-17
• Study First Submitted QC: 2005-08-17
• Study First Posted: 2005-08-19
• Study Start: 2006-09
• Primary Completion: 2009-09
• Study Completion: 2009-09
• Results First Submitted: 2013-05-29
• Status Verified: 2013-10
• Results First Submitted QC: 2013-10-30
• Last Update Submitted: 2013-10-30
• Results First Posted: 2013-12-20
• Last Update Posted: 2013-12-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 382

Inclusion Criteria

1. Age 18 years or older.

2. Diagnosed with schizophrenia or schizoaffective disorder by the Structured Clinical Interview for Diagnosis (SCID) (Spitzer and First et al., 1996).

3. Patients should

   1. have been hospitalized in the two years before study entry on a psychiatric inpatient unit, or
   2. document explicit current evidence of increased use of outpatient services such as additional visits, day treatment or non-hospital residential treatment, increased dosage of medications or addition of concomitant psychotropic medications.

   The b criterion will promptly be adjudicated by the study chairmen on a case-by case basis to insure credibility.

4. .Adequate transportation is available and the participant lives within a travel time of less than 1.5 hours, allowing attendance at all scheduled visits.

5. Use of an acceptable method of birth control by female patients who have a possibility of becoming pregnant (safety concerns).

6. Able to demonstrate decisional capacity in order to give informed consent as assessed by the MacArthur Competence Assessment Tool (MacCAT) (Appelbaum and Grisso, 1996). Guardian consent is acceptable where applicable.

7. Dually diagnosed patients with both schizophrenia and addictive disorders would be included in this study but should not be in need of acute detoxification for physiologic substance dependence (excluding nicotine) in the past 30 days.

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Exclusion Criteria

1. Physiologic substance dependence requiring detoxification (excluding nicotine) in the past 30 days (substance abuse is not an exclusion).
2. Intolerance of risperidone.
3. Intolerance of intramuscular injection.
4. Current treatment with depot antipsychotic medication.
5. Current treatment with oral clozapine or presence of refractory schizophrenia that, in the treating psychiatrist's opinion, requires clozapine.
6. Hepatic or renal problems AST or ALT (>2 times upper limit of normal);
7. Elevated bilirubin (>1.2), BUN (>24), creatinine (>1.7).
8. Unstable, serious medical condition or one requiring acute medical treatment, or anticipation of hospitalization for extended care.
9. Dementia, epilepsy, insulin-dependent diabetes, anticoagulation with coumadin.
10. Unstable living arrangements or not planning to remain in the area for the next year.
11. Legal entanglements or pending legal charges with potential of incarceration.
12. Assault or suicide gesture currently needing acute intervention.
13. Concurrent participation in another clinical trial with an investigational drug during the last 30 days.
14. Pregnant or lactating women or women planning to become pregnant.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1	IM risperidone	long-acting injectable risperidone
Arm 2	oral antipsychotic medication	oral antipsychotic medication

Primary Outcome Measures

Name	Time	Method
Hospitalization-free Survival - Time to Event	From randomization until date of first re-hospitalization, assessed up to 24 months	A hospitalization-free survival was defined as the time from the date of randomization to the time of a psychiatric hospitalization (in both VA and non-VA hospitals) or, in the case of patients who were hospitalized at randomization, the time from the date of discharge from the initial stay to subsequent hospitalization. Patients without an event were censored at 24 months after the date of randomization.
Hazard Ratio for Hospitalization	24 months	Hazard ratio of LAI versus Oral for psychiatric hospitalization (in both VA and non-VA hospitals), after randomization up to 24 months, obtained from a Cox proportional hazards model.

Trial Locations

Locations (19)

VA Medical Center, Tuscaloosa; 🇺🇸 Tuscaloosa, Alabama, United States

Jesse Brown VAMC (WestSide Division); 🇺🇸 Chicago, Illinois, United States

VA Medical Center, Kansas City MO; 🇺🇸 Kansas City, Missouri, United States

VA Palo Alto Health Care System; 🇺🇸 Palo Alto, California, United States

VA Medical Center, Cleveland; 🇺🇸 Cleveland, Ohio, United States

VA Medical Center, Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

VA Medical Center, Minneapolis; 🇺🇸 Minneapolis, Minnesota, United States

VA Medical Center, Omaha; 🇺🇸 Omaha, Nebraska, United States

Central Texas Veterans Health Care System - Waco; 🇺🇸 Waco, Texas, United States

VA Medical Center, Long Beach; 🇺🇸 Long Beach, California, United States

VA Medical Center, Jamaica Plain Campus; 🇺🇸 Boston, Massachusetts, United States

VA Connecticut Health Care System (West Haven); 🇺🇸 West Haven, Connecticut, United States

VA Medical Center, Augusta; 🇺🇸 Augusta, Georgia, United States

VA Medical Center, Miami; 🇺🇸 Miami, Florida, United States

John D. Dingell VA Medical Center, Detroit; 🇺🇸 Detroit, Michigan, United States

New York Harbor HCS; 🇺🇸 New York, New York, United States

Michael E. DeBakey VA Medical Center (152); 🇺🇸 Houston, Texas, United States

New Mexico VA Health Care System, Albuquerque; 🇺🇸 Albuquerque, New Mexico, United States

VA Puget Sound Health Care System, Seattle; 🇺🇸 Seattle, Washington, United States