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Clozapine for the Prevention of Violence in Schizophrenia: a Randomized Clinical Trial (REVISIT-C)

Primary Purpose

Schizophrenia, Schizoaffective Disorder

Status

Recruiting

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Clozapine

treatment as usual

About this trial

This is an interventional treatment trial for Schizophrenia

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Diagnostic and Statistical Manual-5 (DSM-5) diagnosis of schizophrenia or schizoaffective disorder by the Structured Clinical Interview for DSM-5 (SCID-5)
commission of a minor or serious act of violence as measured by the MCVI in the last six months
willing and able to provide informed consent
medically stable in judgment of physician providing study treatment
appropriate for treatment with either clozapine or TAU, i.e., that there is clinical equipoise between the two treatment options. Individuals who are currently medication free or on any antipsychotic, with the exception of clozapine or long-acting injectable medication with a dosing interval of more than 30 days will be eligible

Exclusion Criteria:

An unstable of serious medical or neurological condition including a myeloproliferative disorder or condition that surprises the bone marrow
A history of intolerance/allergy to clozapine (e.g., agranulocytosis, small bowel obstruction, or myocarditis)
A history of intellectual impairment
pregnant or lactating women; women who are able to become pregnant but who are not willing to sue effective methods of birth control
Individuals who score a 3, 4, or 5 within the previous month on the suicidal ideation section of the Columbia Suicide Severity Rating Scale (CSSRS), have any suicidal behavior (not including Not Suicidal Self Injury) within the previous 3 months, or are, in the opinion of the investigator, at too high of a risk for suicide to be safety treated in a randomized trial in which they may not be treated with clozapine
Documented intolerance to or lack of any therapeutic benefit with clozapine after a full trial

Sites / Locations

University of California, Los Angeles
Augusta University Research Institute, Inc.
University of Maryland School of Medicine
NYU Langone Medical Center
New York State Psychiatric InstituteRecruiting
Manhattan Psychiatric Center
University of North Carolina at Chapel Hill

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Clozapine

Treatment as usual

Arm Description

treatment with clozapine naturalistically administered (as per clinical guideline).

open label naturalistic treatment as usual with any antipsychotic other than clozapine

Outcomes

Primary Outcome Measures

Effectiveness outcome: Violent acts

violent acts as measured by the MacArthur Community Violence Interview

Target engagement outcome: Excitement Factor of the Positive and Negative Syndrome Scale (PANSS)

a composite of the scores of excitement, uncooperativeness, poor impulse control, and hostility)

Secondary Outcome Measures

Effect on aggression

examine the effects of clozapine vs TAU on aggression as measured by the Point Subtraction Aggression Paradigm

Positive symptoms and substance use

explore effects of clozapine vs TAU on the positive symptom sub scale of the PANSS and alcohol and illicit substance use, how these effects influence the risk for violent acts, and the degree to which clozapine's effects on the Excitement Factor of the PANSS are independent of its effects on total positive symptoms and substance use.

Full Information

NCT ID

NCT05208190

First Posted

January 12, 2022

Last Updated

March 27, 2023

Sponsor

New York State Psychiatric Institute

Collaborators

National Institute of Mental Health (NIMH)

1. Study Identification

Unique Protocol Identification Number

NCT05208190

Brief Title

Clozapine for the Prevention of Violence in Schizophrenia: a Randomized Clinical Trial

Acronym

REVISIT-C

Official Title

Clozapine for the Prevention of Violence in Schizophrenia: a Randomized Clinical Trial

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Recruiting

Study Start Date

March 17, 2022 (Actual)

Primary Completion Date

January 23, 2027 (Anticipated)

Study Completion Date

February 28, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

New York State Psychiatric Institute

Collaborators

National Institute of Mental Health (NIMH)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Two-hundred and eighty individuals with schizophrenia who have a recent history of violent acts will be randomized in this 2-arm, parallel-group, 24-week, open-label, 7-site clinical trial to examine the effects of treatment with clozapine vs antipsychotic treatment as usual (TAU) for reducing the risk of violent acts in real-world settings

Detailed Description

This is a single-blind, open-label, randomized, active comparator (TAU) controlled clinical trial to examine the effects of clozapine vs. TAU on the risk for violent acts as measured by the MacArthur Community Violence Interview (MCVI) and to examine the effects of clozapine vs. TAU on the Excitement Factor of the PANSS. Adults age 18-65 with schizophrenia or schizoaffective disorder who have committed a violent act within 6 months and are appropriate for treatment with clozapine or TAU will receive treatment for 24 weeks which will be naturalistically administered. Participants will also participate in assessments and appropriate medical monitoring which will include blood draws, pharmacokinetic blood samples, and physical exams, etc. Cox proportional hazards survival modeling will be used to test the association between treatment group and time until first violent act after randomization (i.e., number of weeks form randomization to violent act).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Schizophrenia, Schizoaffective Disorder

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Model Description

single-blind, open-label, randomized, active comparator (TAU) controlled clinical trial

Masking

Outcomes Assessor

Masking Description

Blinded raters and a blinded adjudication committee to ensure that the outcome is valid

Allocation

Randomized

Enrollment

280 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Clozapine

Arm Type

Experimental

Arm Description

treatment with clozapine naturalistically administered (as per clinical guideline).

Arm Title

Treatment as usual

Arm Type

Active Comparator

Arm Description

open label naturalistic treatment as usual with any antipsychotic other than clozapine

Intervention Type

Drug

Intervention Name(s)

Clozapine

Other Intervention Name(s)

clozaril

Intervention Description

treatment will occur naturalistically, as per standard clinical guidelines

Intervention Type

Drug

Intervention Name(s)

treatment as usual

Intervention Description

naturalistic treatment with any other antipsychotic medication except clozapine

Primary Outcome Measure Information:

Title

Effectiveness outcome: Violent acts

Description

violent acts as measured by the MacArthur Community Violence Interview

Time Frame

Time to violent act from randomization to treatment completion (24 weeks)

Title

Target engagement outcome: Excitement Factor of the Positive and Negative Syndrome Scale (PANSS)

Description

a composite of the scores of excitement, uncooperativeness, poor impulse control, and hostility)

Time Frame

Randomization to end of study treatment (24 weeks)

Secondary Outcome Measure Information:

Title

Effect on aggression

Description

examine the effects of clozapine vs TAU on aggression as measured by the Point Subtraction Aggression Paradigm

Time Frame

Randomization to end of treatment (24 weeks)

Title

Positive symptoms and substance use

Description

Time Frame

Randomization to end of treatment (24 weeks)

Other Pre-specified Outcome Measures:

Title

Interventions to Prevent Violence

Description

examine the effects of clozapine vs TAU on interventions to prevent violence based on a querying clinicians treating patients about interventions to prevent violence at weeks 4, 8, 16 and 24

Time Frame

Randomization to end of treatment (24 weeks)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Diagnostic and Statistical Manual-5 (DSM-5) diagnosis of schizophrenia or schizoaffective disorder by the Structured Clinical Interview for DSM-5 (SCID-5) commission of a minor or serious act of violence as measured by the MCVI in the last six months willing and able to provide informed consent medically stable in judgment of physician providing study treatment appropriate for treatment with either clozapine or TAU, i.e., that there is clinical equipoise between the two treatment options. Individuals who are currently medication free or on any antipsychotic, with the exception of clozapine or long-acting injectable medication with a dosing interval of more than 30 days will be eligible Exclusion Criteria: An unstable of serious medical or neurological condition including a myeloproliferative disorder or condition that surprises the bone marrow A history of intolerance/allergy to clozapine (e.g., agranulocytosis, small bowel obstruction, or myocarditis) A history of intellectual impairment pregnant or lactating women; women who are able to become pregnant but who are not willing to sue effective methods of birth control Individuals who score a 3, 4, or 5 within the previous month on the suicidal ideation section of the Columbia Suicide Severity Rating Scale (CSSRS), have any suicidal behavior (not including Not Suicidal Self Injury) within the previous 3 months, or are, in the opinion of the investigator, at too high of a risk for suicide to be safety treated in a randomized trial in which they may not be treated with clozapine Documented intolerance to or lack of any therapeutic benefit with clozapine after a full trial

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Ragy Girgis

Phone

646-774-5553

ragy.girgis@nyspi.columbia.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ragy Girgis, MD

Organizational Affiliation

New York State Psychiatric Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of California, Los Angeles

City

Los Angeles

State/Province

California

ZIP/Postal Code

90024

Country

United States

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Alex Kopelowicz, MD

Phone

818-837-8150

akopel@ucla.edu

Facility Name

Augusta University Research Institute, Inc.

City

Augusta

State/Province

Georgia

ZIP/Postal Code

30912

Country

United States

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Joseph McEvoy, MD

Phone

706-792-7021

jmcevoy@augusta.edu

Facility Name

University of Maryland School of Medicine

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21201

Country

United States

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Deanna Kelly, PharmD

Phone

410-402-6861

dlkelly@som.umaryland.edu

Facility Name

NYU Langone Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10016

Country

United States

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Donald Goff

Phone

646-754-4843

donald.goff@nyulangone.org

Facility Name

New York State Psychiatric Institute

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ragy R Girgis, MD

Phone

646-774-5553

rg2290@columbia.edu

First Name & Middle Initial & Last Name & Degree

Ragy R Girgis, MD

First Name & Middle Initial & Last Name & Degree

Scott Stroup, MD

Facility Name

Manhattan Psychiatric Center

City

New York

State/Province

New York

ZIP/Postal Code

10035

Country

United States

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jean-Pierre Lindenmayer, MD

Phone

212-249-2720

jean-pierre.lindenmayer@nki.rfmh.org

Facility Name

University of North Carolina at Chapel Hill

City

Chapel Hill

State/Province

North Carolina

ZIP/Postal Code

27599

Country

United States

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Fred Jarskog, MD

Phone

919-842-7683

jarskog@med.unc.edu

12. IPD Sharing Statement

Learn more about this trial

Clozapine for the Prevention of Violence in Schizophrenia: a Randomized Clinical Trial

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