Intensified treatment for schizophrenia after first treatment failure
A Randomised, Controlled Trial to Investigate the Effect of a Six Week Intensified Pharmacological Treatment for Schizophrenia Compared to Treatment as Usual in Subjects Who Had a First-time Treatment Failure on Their First-line Treatment.
This study is testing if starting clozapine sooner can help people with schizophrenia who didn't respond to their first treatment feel better and improve their quality of life.
Quick facts
| Phase | Phase 4 |
|---|---|
| Study type | Interventional |
| Enrollment | 418 (estimated) |
| Ages | 18 Years to 70 Years |
| Sex | All |
| Sponsor | UMC Utrecht Academic / other |
| Locations | 13 sites (Innsbruck and 12 other locations) |
| Trial ID | NCT05958875 on ClinicalTrials.gov |
What this trial studies
This clinical trial investigates the effects of a six-week intensified pharmacological treatment using clozapine compared to standard treatment for patients with schizophrenia who have experienced their first treatment failure. The study aims to determine if initiating clozapine earlier in the treatment process can lead to better outcomes for patients who have not responded to first-line antipsychotics. Participants will be monitored closely due to the potential risks associated with clozapine, but the goal is to improve the quality of life and reduce the burden of the illness. The trial will include both inpatients and outpatients aged 18 to 70 who meet specific diagnostic criteria.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18 to 70 who have a primary diagnosis of schizophrenia or related disorders and have experienced their first treatment failure with a first-line antipsychotic.
Not a fit: Patients who have not yet experienced a treatment failure or those with contraindications to clozapine may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could provide a more effective treatment option for patients with treatment-resistant schizophrenia, potentially improving their quality of life.
How similar studies have performed: Other studies have shown that earlier use of clozapine can be beneficial for treatment-resistant schizophrenia, suggesting that this approach may have merit.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
1. In- or out patients, at least 18 years of age up until 70.
2. Being willing and able to provide written informed consent. Having a legal guardian to cosign is allowed. Informed consent will be signed at visit 1, before any study procedure.
3. Female subjects of child bearing potential must use effective contraception during the trial as per the requirements of the applicable SmPCs and should have a negative pregnancy test at visit 1 or 2 (before randomisation; section 8.2).
4. Meeting diagnostic criteria for a primary diagnosis of schizophrenia, schizoaffective disorder, or schizophreniform disorder, according to DSM-5. The primary diagnosis will be confirmed by the Mini International Neuropsychiatric Interview (MINI v7.0.2).
5. Subject experiences a treatment failure due to lack of efficacy in the current episode, as confirmed by a CGI-I ≥3; preferably this treatment is a first-line pharmacotherapeutic agent for the primary DSM-5 diagnosis, and was prescribed for at least 4 weeks within an effective dose range as specified in the Summary of Product Characteristics (SmPCs). However, other lines of treatment are accepted as well.
6. Subject and clinician intend to change pharmacotherapeutic treatment.
7. A minimum symptom severity threshold needs to be present (moderate level; see below) and subject needs to experience functional impairment.
* The minimum symptom severity threshold is at least 2 PANSS positive or negative items with a score of 4, or at least one PANSS positive or negative item with a score of 5.
* Functional impairment is defined as a score of 5 or higher on any of the three scales of the Sheehan Disability Scale (SDS).
Exclusion criteria:
1. Being pregnant or breastfeeding.
2. Subject has used clozapine in the past.
3. Subject has a known intolerance to clozapine or to all TAU medication options.
4. Meeting any of the contraindications of clozapine or to all TAU medication options, as specified within the applicable SmPC.
5. Subject has participated in another clinical trial in which the subject received an experimental or investigational drug or agent within 30 days before visit 1.
6. Subject experiences any other significant disease or disorder which, in the opinion of the investigator, may either put the subjects at risk because of participation in the trial, or may influence the result of the trial, or the subject's ability to participate in the trial.
7. Subjects with active suicidal ideation with some intent to act, without specific plan ("Yes" to question 4 of the Columbia-Suicide Severity Rating Scale (C-SSRS)) or active suicidal ideation with specific plan and intent ("Yes" to question 5 of the C-SSRS), followed by an assessment by the treating clinician who determines it is not safe for the subject to participate in the study
8. Subject meets criteria for current substance use disorder, as confirmed by the Mini International Neuropsychiatric Interview (MINI v7.0.2). Nicotine dependency is allowed, as well as mild and moderate alcohol and/or cannabis use disorder (as defined by MINI v7.0.2). Severe alcohol and/or cannabis use disorder are not allowed.
9. Subjects have not been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
10. Subjects who meet the modified Andreasen criteria for remission.
11. Subjects that have any clinically significant abnormal values on the local laboratory test (especially ANC/WBC and liver values), electrocardiogram (ECG) or physician examinations.
12. Subjects dependent on the sponsor, investigator or trial site must be excluded from participation in advance
Where this trial is running
Innsbruck and 12 other locations
- Medical University Innsbruck — Innsbruck, Austria (Recruiting)
- Bezirkskliniken Schwaben, Bezirkskrankenhaus Augsburg — Augsburg, Germany (Not_yet_recruiting)
- Universitätsklinik für Psychiatrie und Psychotherapie Bielefeld — Bielefeld, Germany (Recruiting)
- LWL-Klinik Dortmund, Bereich Forschung & Wissenschaft — Dortmund, Germany (Recruiting)
- University Hospital Frankfurt am Main - Goethe University — Frankfurt am Main, Germany (Recruiting)
- Klinik für Psychiatrie und Psychotherapie der Universitätsmedizin Mainz — Mainz, Germany (Recruiting)
- Westfälische Wilhelms-Universität Münster — Münster, Germany (Recruiting)
- Universita degli Studi di Brescia — Brescia, Italy (Recruiting)
- University of Cagliari — Cagliari, Italy (Recruiting)
- Università degli studi della Campania Luigi Vanvitelli — Naples, Italy (Recruiting)
- Azienda Ospedaliero-Universitaria "Città della Salute e della Scienza di Torino" — Turin, Italy (Recruiting)
- Fundació Clínic per a la Recerca Biomèdica — Barcelona, Spain (Recruiting)
- King's College London, Psychiatry & Cognitive Neuroscience — London, United Kingdom (Recruiting)
Study contacts
- Study coordinator: Inge Winter, Dr.
- Email: i.winter@umcutrecht.nl
- Phone: +31875553227
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.