Clozapine for Schizophrenia
(REVISIT-C Trial)
Recruiting in Palo Alto (17 mi)
+6 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: New York State Psychiatric Institute
Must be taking: Antipsychotics
Must not be taking: Clozapine, Long-acting injectables
Disqualifiers: Unstable medical condition, Pregnancy, Suicide risk, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?This trial is testing whether clozapine can reduce violent behavior more effectively than usual treatments in adults with schizophrenia who have recently been violent. Clozapine helps by balancing brain chemicals to manage symptoms. The study will last for several months and include regular medical check-ups. Clozapine has been shown to reduce violent and aggressive behavior in patients with schizophrenia, especially those who are treatment-resistant.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but you can participate if you are currently medication-free or on any antipsychotic, except clozapine or long-acting injectables with a dosing interval of more than 30 days.
What data supports the effectiveness of the drug Clozapine for schizophrenia?
Clozapine is considered the most effective drug for managing treatment-resistant schizophrenia, showing significant improvement in symptoms compared to other second-generation antipsychotic drugs, especially in patients who have not responded well to at least two other antipsychotic medications.
12345Is clozapine safe for use in humans?
Clozapine is generally safe for humans when used carefully, but it can have serious side effects like blood problems, heart issues, and seizures. Regular monitoring of blood cells and other health checks are important to manage these risks.
678910What makes the drug clozapine unique for treating schizophrenia?
Clozapine is unique because it is the only antipsychotic drug specifically approved for treatment-resistant schizophrenia, meaning it is used when other treatments have failed. It is also known for having fewer movement-related side effects compared to traditional antipsychotic drugs.
211121314Eligibility Criteria
This trial is for adults with schizophrenia or schizoaffective disorder who have been violent recently. They must be medically stable, able to consent, and not on certain long-term medications. Pregnant women, those intolerant to clozapine, with serious medical conditions or high suicide risk are excluded.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)
medically stable in judgment of physician providing study treatment
You have committed a violent act in the past six months, as determined by the MCVI assessment.
+2 more
Exclusion Criteria
A history of intolerance/allergy to clozapine (e.g., agranulocytosis, small bowel obstruction, or myocarditis)
I do not have a serious condition affecting my blood or nervous system.
I tried clozapine without success or had side effects.
+3 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive treatment with clozapine or treatment as usual (TAU) for 24 weeks
24 weeks
Regular visits for assessments and medical monitoring
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study compares the effectiveness of clozapine versus usual antipsychotic treatments in reducing violence among individuals with schizophrenia over a 24-week period across seven sites. Participants will be randomly assigned to one of the two treatment groups.
2Treatment groups
Experimental Treatment
Active Control
Group I: ClozapineExperimental Treatment1 Intervention
treatment with clozapine naturalistically administered (as per clinical guideline).
Group II: Treatment as usualActive Control1 Intervention
open label naturalistic treatment as usual with any antipsychotic other than clozapine
Clozapine is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Clozaril for:
- Schizophrenia
- Borderline Personality Disorder
- Paranoid Disorder
🇪🇺 Approved in European Union as Clozapine for:
- Schizophrenia
- Treatment-resistant schizophrenia
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Maryland School of MedicineBaltimore, MD
Manhattan Psychiatric CenterNew York, NY
University of California, Los AngelesLos Angeles, CA
Augusta University Research Institute, Inc.Augusta, GA
More Trial Locations
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Who Is Running the Clinical Trial?
New York State Psychiatric InstituteLead Sponsor
National Institute of Mental Health (NIMH)Collaborator
References
Clozapine resistance: augmentation strategies. [2022]Clozapine (CLZ) is not effective in more than 50% of treatment-resistant schizophrenic patients. In these cases, several pharmacological strategies are used in clinical practice, with different levels of evidence for both safety and efficacy.
Bioequivalence of Generic and Brand Name Clozapine in Korean Schizophrenic Patients: A Randomized, Two-Period, Crossover Study. [2020]Clozapine is the treatment of choice for refractory schizophrenia. The aim of this study was to compare the pharmacokinetics of the brand name (Clozaril) formulation and a generic formulation (Clzapine) of clozapine in Korean schizophrenic patients.
Evaluation of bioequivalence between generic and brand-name clozapine in Chinese schizophrenic patients: A randomized, two-period, crossover study. [2021]Clozapine is the most effective therapy for schizophrenia. This study compared the bioequivalence of a generic formulation of clozapine (ChangZhou Pharmaceutical Factory Co. Ltd. Jiangsu, China) to the brand name formulation (Clozaril, HLS Therapeutics, Inc., Philadelphia, PA, USA) after multiple doses in Chinese schizophrenic patients.
CYP2C19*17 protects against metabolic complications of clozapine treatment. [2022]Clozapine (CZ) is the most effective drug for managing treatment-resistant schizophrenic disorders. Its use has been limited due to adverse effects, which include weight gain and new-onset diabetes, but the incidence of these varies between patients.
Randomized controlled trial of effect of prescription of clozapine versus other second-generation antipsychotic drugs in resistant schizophrenia. [2022]There is good evidence that clozapine is more efficacious than first-generation antipsychotic drugs in resistant schizophrenia. It is less clear if clozapine is more effective than the other second-generation antipsychotic (SGA) drugs. A noncommercially funded, pragmatic, open, multisite, randomized controlled trial was conducted in the United Kingdom National Health Service (NHS). Participants were 136 people aged 18-65 with DSM-IV schizophrenia and related disorders whose medication was being changed because of poor clinical response to 2 or more previous antipsychotic drugs. Participants were randomly allocated to clozapine or to one of the class of other SGA drugs (risperidone, olanzapine, quetiapine, amisulpride) as selected by the managing clinician. Outcomes were assessed blind to treatment allocation. One-year assessments were carried out in 87% of the sample. The intent to treat comparison showed no statistically significant advantage for commencing clozapine in Quality of Life score (3.63 points; CI: 0.46-7.71; p = .08) but did show an advantage in Positive and Negative Syndrome Scale (PANSS) total score that was statistically significant (-4.93 points; CI: -8.82 to -1.05; p = .013) during follow-up. Clozapine showed a trend toward having fewer total extrapyramidal side effects. At 12 weeks participants who were receiving clozapine reported that their mental health was significantly better compared with those receiving other SGA drugs. In conclusion, in people with schizophrenia with poor treatment response to 2 or more antipsychotic drugs, there is an advantage to commencing clozapine rather than other SGA drugs in terms of symptom improvement over 1 year.
Clozapine is the approved option in treatment-resistant schizophrenia and requires careful management. [2023]Clozapine is the only agent approved for treatment-resistant schizophrenia, but is underprescribed. Its adverse drug event (ADE) profile and patient monitoring requirements can discourage its use, but the benefits of clozapine generally outweigh its risks, as most ADEs are manageable. Careful patient assessment, gradual titration, minimum effective dosages, therapeutic drug monitoring and checks of neutrophils, cardiac enzymes and ADE symptoms are recommended. Neutropenia is common but does not necessarily warrant permanent clozapine cessation.
Clozapine Monitoring in Clinical Practice: Beyond the Mandatory Requirement. [2022]Clozapine is effective in treatment resistant schizophrenia; however, it is underutilised probably because of its side effects. The side effects are also the potential reasons for clozapine discontinuation. A mandatory requirement for its use is regular monitoring of white blood cell count and absolute neutrophil count. However there are many side effects that need monitoring in clinical practice considering their seriousness. This article tries to summarise the clinical concerns surrounding the serious side effects of clozapine some of which are associated with fatalities and presents a comprehensive way to monitor patients on clozapine in clinical practice. It emphasizes the need to broaden the monitoring beyond the mandatory investigations. This may help in improving the safety in clinical practice and increasing clinician confidence for greater and appropriate use of this effective intervention.
A review of clozapine safety. [2013]Clozapine is a distinctive antipsychotic agent, having a unique clinical profile and an idiosyncratic safety profile. More so than with other agents, the weighting of its adverse event profile is critical, in order to counterbalance its clear clinical advantages. The safety issues with clozapine are in a number of areas, some of which are considered medical emergencies and potentially life-threatening. These include haematological (neutropenia and agranulocytosis), CNS (seizures), cardiovascular (myocarditis and cardiomyopathy), metabolic (diabetes), gastrointestinal and neuromuscular. Understanding the safety profile of clozapine allows an informed use of the agent that can maximise its clear clinical benefit and minimise the known risks.
Monitoring the safe use of clozapine: a consensus view from Victoria, Australia. [2018]Clozapine is an important antipsychotic agent that has a unique profile of clinical benefits, but that has also been associated with several serious and potentially life-threatening safety concerns. In order to minimise the impact of haematological adverse events, health professionals treating patients with clozapine are currently required to register their patients on a centrally administered data network and to conform to strict protocols. The consensus statement documented in this article extends existing protocols by recommending monitoring of patients treated with clozapine for additional adverse effects during treatment. This consensus statement reflects the current practice at five major public psychiatric hospitals in Victoria, Australia, for the monitoring and management of clozapine-related adverse events, and has been implemented at these sites because of emerging safety concerns associating clozapine with cardiovascular and metabolic adverse effects.
Clozapine Management in Schizophrenia Inpatients: A 5-Year Prospective Observational Study of Its Safety and Tolerability Profile. [2022]Clozapine is well known for its efficacy and clinical superiority compared to other antipsychotics in treatment-resistant schizophrenia (TRS). However, it is frequently underutilized worldwide because of its acute adverse events, as well as for its long-term cardiometabolic and hematological consequences.
Update on the clinical efficacy and side effects of clozapine. [2022]Clozapine (CLOZ) is an atypical antipsychotic drug being used with increasing frequency throughout the world and has recently been commercially marketed in the United States. Its unique properties make it a promising but challenging drug to use in the treatment of schizophrenia. In order to use CLOZ most effectively and efficiently, clinicians must be aware of its potential benefits and risks. This report is a review and critical evaluation of current knowledge regarding the clinical efficacy and side effects of CLOZ. Although CLOZ has proven to be effective in some treatment-refractory schizophrenic patients and to produce relatively few extrapyramidal side effects compared to classical neuroleptic drugs, several issues require further investigation including what defines neuroleptic intolerance, the optimal dose range, and the appropriate duration of a CLOZ treatment trial. Similarly, studies are needed to determine what role CLOZ should have in the treatment of patients with predominantly negative symptoms and those patients who are only partially responsive to standard neuroleptics. In addition, important questions remain as to what other conditions might be indications for CLOZ, for example, schizoaffective disorder, affective psychoses, and idiopathic Parkinson's disease.
Clozapine. [2016]Clozapine is an atypical agent for intractable schizophrenia which was introduced into the UK at the beginning of 1990. Its lack of extrapyramidal side effects and its action on negative symptoms single it out from conventional neuroleptics. This article describes the drug's development/special monitoring and dispensing arrangements, and gives advice on how it can best be utilized.
A systematic review and meta-analysis of the association between clozapine and norclozapine serum levels and peripheral adverse drug reactions. [2021]Clozapine is the most effective antipsychotic for treatment-refractory schizophrenia for reducing positive psychotic symptoms. It is associated with a reduction in hospitalisation and overall mortality. In spite of this, clozapine remains underutilised due to its complex adverse drug reaction (ADR) profile.
Adherence to treatment guidelines in clinical practice: study of antipsychotic treatment prior to clozapine initiation. [2021]Clozapine is the only antipsychotic drug licensed for treatment-resistant schizophrenia but its use is often delayed. Since previous studies, national guidelines on the use of clozapine and other antipsychotics have been disseminated to clinicians.