Long-Acting Injectable Risperidone in the Treatment of Schizophrenia

NCT ID: NCT00132314

Last Updated: 2013-12-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 382 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-09-30
• Study Completion Date: 2009-09-30

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.

Conditions

Schizoaffective Disorder; Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1

long-acting injectable risperidone

Group Type: EXPERIMENTAL

IM risperidone

Intervention Type: DRUG

long-acting injectable risperidone

Arm 2

oral antipsychotic medication

Group Type: ACTIVE_COMPARATOR

oral antipsychotic medication

Intervention Type: DRUG

doctor's choice (excluding other long-acting injectable medications but not specifying any particular oral agents or dosages)

Interventions

IM risperidone

long-acting injectable risperidone

Intervention Type: DRUG

oral antipsychotic medication

doctor's choice (excluding other long-acting injectable medications but not specifying any particular oral agents or dosages)

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

US Department of Veterans Affairs

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert A. Rosenheck, AB MD

Role: STUDY_CHAIR

VA Connecticut Health Care System (West Haven)

Locations

VA Medical Center, Tuscaloosa

Tuscaloosa, Alabama, United States

VA Medical Center, Long Beach

Long Beach, California, United States

VA Palo Alto Health Care System

Palo Alto, California, United States

VA Connecticut Health Care System (West Haven)

West Haven, Connecticut, United States

VA Medical Center, Miami

Miami, Florida, United States

VA Medical Center, Augusta

Augusta, Georgia, United States

Jesse Brown VAMC (WestSide Division)

Chicago, Illinois, United States

VA Medical Center, Jamaica Plain Campus

Boston, Massachusetts, United States

John D. Dingell VA Medical Center, Detroit

Detroit, Michigan, United States

VA Medical Center, Minneapolis

Minneapolis, Minnesota, United States

VA Medical Center, Kansas City MO

Kansas City, Missouri, United States

VA Medical Center, Omaha

Omaha, Nebraska, United States

New Mexico VA Health Care System, Albuquerque

Albuquerque, New Mexico, United States

New York Harbor HCS

New York, New York, United States

VA Medical Center, Cleveland

Cleveland, Ohio, United States

VA Medical Center, Philadelphia

Philadelphia, Pennsylvania, United States

Michael E. DeBakey VA Medical Center (152)

Houston, Texas, United States

Central Texas Veterans Health Care System - Waco

Waco, Texas, United States

VA Puget Sound Health Care System, Seattle

Seattle, Washington, United States

Countries

United States

References

Rosenheck RA, Krystal JH, Lew R, Barnett PG, Thwin SS, Fiore L, Valley D, Huang GD, Neal C, Vertrees JE, Liang MH; CSP 555 Research Group. Challenges in the design and conduct of controlled clinical effectiveness trials in schizophrenia. Clin Trials. 2011 Apr;8(2):196-204. doi: 10.1177/1740774510392931. Epub 2011 Jan 26.

Reference Type: RESULT

PMID: 21270143 (View on PubMed)

Rosenheck RA, Krystal JH, Lew R, Barnett PG, Fiore L, Valley D, Thwin SS, Vertrees JE, Liang MH; CSP555 Research Group. Long-acting risperidone and oral antipsychotics in unstable schizophrenia. N Engl J Med. 2011 Mar 3;364(9):842-51. doi: 10.1056/NEJMoa1005987.

Reference Type: RESULT

PMID: 21366475 (View on PubMed)

Barnett PG, Scott JY, Rosenheck RA; CSP 555 Study Group. How do clinical trial participants compare to other patients with schizophrenia? Schizophr Res. 2011 Aug;130(1-3):34-9. doi: 10.1016/j.schres.2011.03.033. Epub 2011 Apr 22.

Reference Type: RESULT

PMID: 21514794 (View on PubMed)

Barnett PG, Scott JY, Krystal JH, Rosenheck RA; CSP 555 Research Group. Cost and cost-effectiveness in a randomized trial of long-acting risperidone for schizophrenia. J Clin Psychiatry. 2012 May;73(5):696-702. doi: 10.4088/JCP.11m07070.

Reference Type: RESULT

PMID: 22697193 (View on PubMed)

Thwin SS, Hermes E, Lew R, Barnett P, Liang M, Valley D, Rosenheck R. Assessment of the minimum clinically important difference in quality of life in schizophrenia measured by the Quality of Well-Being Scale and disease-specific measures. Psychiatry Res. 2013 Oct 30;209(3):291-6. doi: 10.1016/j.psychres.2013.01.016. Epub 2013 Mar 7.

Reference Type: RESULT

PMID: 23473656 (View on PubMed)

Hoblyn JC, Rosenheck RA, Leatherman S, Weil L, Lew R; CSP 555 Investigator Group. Veteran subjects willingness to participate in schizophrenia clinical trials. Psychiatr Q. 2013 Jun;84(2):209-18. doi: 10.1007/s11126-012-9240-4.

Reference Type: DERIVED

PMID: 23143523 (View on PubMed)

Other Identifiers

555

Identifier Type: -

Identifier Source: org_study_id