RecruitingPhase IVInterventional

A clinical study to investigate whether third-line treatments work better as a second-line treatment for people diagnosed with schizophrenia

When people are treated for schizophrenia or similar conditions, doctors usually start with a standard antipsychotic medicine. If that first medicine does not help enough, guidelines suggest trying another standard option before considering clozapine, a medication known to be especially effective. This clinical trial is testing whether starting clozapine earlier—as the very next step after the first medicine fails—helps people recover better and faster. Led by researchers at King’s College London, the study compares clozapine with the usual choice of a second medication over 6 weeks. Participants are aged 18 to 70 and will receive close health checks, including regular blood tests and heart tracings, just as they would in routine NHS care. The aim is to find out if this earlier switch reduces symptoms, prevents hospital stays, and improves overall quality of life without adding extra safety risks.

At a glance

Status

Recruiting

Phase

Phase IV

Sponsor

University Medical Center Utrecht

Enrolment target

418

Start

31 Aug 2023

Estimated completion

01 Dec 2026

Schizophrenia, schizoaffective disorder or schizophreniform disorder

What is this study about?

When someone is diagnosed with schizophrenia, finding the right medication often involves trial and error. People are typically prescribed an antipsychotic medicine first. However, if this first medicine does not relieve symptoms well enough, doctors usually try a second standard medicine before exploring stronger treatments. This waiting period can be frustrating and may delay recovery.

Clozapine is an antipsychotic medication that has been used safely for decades. It is widely recognised as the most effective treatment for symptoms that do not respond to standard drugs. At present, it is kept as a 'third-line' choice, meaning people must try and fail two other medications before they can access it. This study, led by King's College London, explores whether offering clozapine earlier—as a 'second-line' treatment—leads to better results.

Waiting through multiple medication trials can lead to repeated relapses, hospital stays, and disruption to work and family life. By testing whether an earlier switch to clozapine helps people recover more quickly, this research could help update clinical guidelines. Ultimately, it aims to give patients the most effective care sooner, helping them regain stability and improve their day-to-day quality of life.

Key takeaways

Tests whether using clozapine as a second treatment works better than waiting to use it as a third option.
Open to adults aged 18 to 70 with schizophrenia whose first medication did not work well enough.
The main trial treatment and monitoring period lasts for 6 weeks.
Includes close medical monitoring, such as heart tracings, physical checks, and regular blood tests.
Participation is entirely voluntary and will not affect your ongoing NHS healthcare.

Who may be eligible?

You may be able to take part if you are between 18 and 70 years of age and have a diagnosis of schizophrenia, schizoaffective disorder, or schizophreniform disorder. You must be able to give your informed consent, or have agreement from a legal representative where local regulations allow.

This trial is specifically for people whose first antipsychotic medicine did not work well enough, despite taking it for at least four weeks at an appropriate dose. You and your doctor must both agree that it is time to switch to a different treatment, and you should still have moderate symptoms that interfere with your daily activities.

For safety reasons, women who could become pregnant must take a pregnancy test before joining and agree to use effective contraception throughout the study. The study team will also carry out standard health and wellbeing checks to make sure taking part is safe and suitable for you.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

I am aged between 18 and 70.
I have been diagnosed with schizophrenia, schizoaffective disorder, or schizophreniform disorder.
I have taken my first antipsychotic medicine for at least 4 weeks, but it has not helped enough.
My doctor and I both agree it is time to switch to a different medicine.
I still experience moderate symptoms that affect my everyday life.
I am willing to attend regular appointments and have routine health checks, including blood tests.

Answer every question to see your result.

What does participation involve?

If you decide to take part, you will be randomly placed into one of two groups. One group will start clozapine, while the other group will receive standard treatment (another commonly used second antipsychotic). The main comparison period lasts for 6 weeks. During this time, you will have regular clinic visits so the medical team can monitor your physical health and mental wellbeing. These visits include standard checks such as blood pressure readings, physical examinations, and heart tracings (ECGs). If you take clozapine, you will also have weekly blood tests to check your white blood cells, which is standard safety practice for this medicine. You will also be asked to complete questionnaires about your symptoms, everyday functioning, and side effects. There is also an optional questionnaire about early life experiences, which you can choose to skip or stop at any time.

Potential risks and benefits

A potential benefit of joining is receiving a treatment known to be highly effective earlier in your care, which may help relieve symptoms faster and reduce the chance of hospital visits. All medicines can cause side effects, and these will be closely tracked by doctors. The main extra requirement for clozapine is weekly blood tests, which can cause slight bruising, but are essential to catch and prevent a rare drop in infection-fighting white blood cells. Taking part is completely voluntary. You are free to leave the study at any time, and doing so will not affect your relationship with your healthcare team or your standard NHS care.

Locations (1)

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Approximate
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Common questions

What is clozapine?

Clozapine is an established antipsychotic medicine used worldwide. It is known to work well for symptoms that have not improved with other treatments.

Why are weekly blood tests needed?

Clozapine carries a small risk of lowering white blood cells, which fight infection. Regular weekly blood tests ensure your levels remain healthy and keep you safe.

Will I definitely receive clozapine if I join?

Not necessarily. A computer randomly decides whether you receive clozapine or another standard second-choice medicine, giving both options a fair comparison.

What if I find the study questionnaires upsetting?

Some questionnaires ask personal questions about your past or feelings. You do not have to answer any question that makes you uncomfortable, and you can stop at any time.

Can I leave the study early if I change my mind?

Yes. You can withdraw from the trial at any point without giving a reason, and your regular NHS medical care will continue as normal.

How to find out more

Oliver Howes

oliver.howes@kcl.ac.uk - Official trial record

Always speak to your GP or specialist before deciding to take part in a study.