Long-Acting Injectable Risperidone in the Treatment of Schizophrenia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00132314
First received: August 17, 2005
Last updated: October 30, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Schizoaffective Disorder
Schizophrenia
Drug: IM risperidone
Drug: oral antipsychotic medication
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: CSP #555 - Long-Acting Injectable Risperidone in the Treatment of Schizophrenia

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • Hospitalization-free Survival - Time to Event [ Time Frame: From randomization until date of first re-hospitalization, assessed up to 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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.


Enrollment: 382
Study Start Date: September 2006
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
long-acting injectable risperidone
Drug: IM risperidone
long-acting injectable risperidone
Active Comparator: Arm 2
oral antipsychotic medication
Drug: oral antipsychotic medication
doctor's choice (excluding other long-acting injectable medications but not specifying any particular oral agents or dosages)

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00132314

  Show 19 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Robert A. Rosenheck, AB MD VA Connecticut Health Care System (West Haven)
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00132314     History of Changes
Other Study ID Numbers: 555
Study First Received: August 17, 2005
Results First Received: May 29, 2013
Last Updated: October 30, 2013
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Schizophrenia
Psychotic Disorders
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Antipsychotic Agents
Risperidone
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Dopamine Antagonists
Dopamine Agents

ClinicalTrials.gov processed this record on September 22, 2014