Long-Acting Injectable Risperidone in the Treatment of Schizophrenia

NCT00132314 | Completed Phase 3 Results DMC

• 1 other identifier: 555
• Study Type: interventional
• Target: 382
• Locations: 1 country
• Sites: 19

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.

Conditions

Schizoaffective Disorder; Schizophrenia

Outcome Measures

Primary Outcomes (2)

• Hospitalization-free Survival - Time to Event

  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.

  From randomization until date of first re-hospitalization, assessed up to 24 months

• Hazard Ratio for Hospitalization

  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.

  24 months

Study Arms (2)

Arm 1

EXPERIMENTAL

long-acting injectable risperidone

Drug: IM risperidone

Arm 2

ACTIVE COMPARATOR

oral antipsychotic medication

Drug: oral antipsychotic medication

Interventions

IM risperidone DRUG

long-acting injectable risperidone

Arm 1

oral antipsychotic medication DRUG

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

Arm 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older.
• Diagnosed with schizophrenia or schizoaffective disorder by the Structured Clinical Interview for Diagnosis (SCID) (Spitzer and First et al., 1996).
• Patients should
• have been hospitalized in the two years before study entry on a psychiatric inpatient unit, or
• 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.
• Adequate transportation is available and the participant lives within a travel time of less than 1.5 hours, allowing attendance at all scheduled visits.
• Use of an acceptable method of birth control by female patients who have a possibility of becoming pregnant (safety concerns).
• 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.
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• US Department of Veterans Affairs: lead

Study Sites (19)

VA Medical Center, Tuscaloosa

Tuscaloosa, Alabama, 35404, United States

Location

VA Medical Center, Long Beach

Long Beach, California, 90822, United States

Location

VA Palo Alto Health Care System

Palo Alto, California, 94304-1290, United States

Location

VA Connecticut Health Care System (West Haven)

West Haven, Connecticut, 06516, United States

Location

VA Medical Center, Miami

Miami, Florida, 33125, United States

Location

VA Medical Center, Augusta

Augusta, Georgia, 30904, United States

Location

Jesse Brown VAMC (WestSide Division)

Chicago, Illinois, 60612, United States

Location

VA Medical Center, Jamaica Plain Campus

Boston, Massachusetts, 02130, United States

Location

John D. Dingell VA Medical Center, Detroit

Detroit, Michigan, 48201, United States

Location

VA Medical Center, Minneapolis

Minneapolis, Minnesota, 55417, United States

Location

VA Medical Center, Kansas City MO

Kansas City, Missouri, 64128, United States

Location

VA Medical Center, Omaha

Omaha, Nebraska, 68105-1873, United States

Location

New Mexico VA Health Care System, Albuquerque

Albuquerque, New Mexico, 87108-5153, United States

Location

New York Harbor HCS

New York, New York, 10010, United States

Location

VA Medical Center, Cleveland

Cleveland, Ohio, 44106, United States

Location

VA Medical Center, Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Michael E. DeBakey VA Medical Center (152)

Houston, Texas, 77030, United States

Location

Central Texas Veterans Health Care System - Waco

Waco, Texas, 76711, United States

Location

VA Puget Sound Health Care System, Seattle

Seattle, Washington, 98108, United States

Location

Related Publications (6)

• 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.

  PMID: 21270143 RESULT

• 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.

  PMID: 21366475 RESULT

• 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.

  PMID: 21514794 RESULT

• 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.

  PMID: 22697193 RESULT

• 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.

  PMID: 23473656 RESULT

• 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.

  PMID: 23143523 DERIVED

MeSH Terms

Conditions

Psychotic Disorders; Schizophrenia

Interventions

Antipsychotic Agents

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Tranquilizing Agents; Central Nervous System Depressants; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Central Nervous System Agents; Therapeutic Uses; Psychotropic Drugs

Results Point of Contact

• Title: Robert Rosenheck, MD
• Organization: VA New England Mental Illness, Research, Education and Clinical Center

Robert.Rosenheck@va.gov

(203) 932-5711

Study Officials

• Robert A. Rosenheck, AB MD

  VA Connecticut Health Care System (West Haven)

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2005
• First Posted: August 19, 2005
• Study Start: September 1, 2006
• Primary Completion: September 1, 2009
• Study Completion: September 1, 2009
• Last Updated: December 20, 2013
• Results First Posted: December 20, 2013

Record last verified: 2013-10

Locations

US (19)