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SchizophreniaPhase 4EULASTNCT02146547

European Long-acting Antipsychotics in Schizophrenia Trial

A Phase 4 study testing Aripiprazole, Aripiprazole depot and Paliperidone in people with Schizophrenia, run by UMC Utrecht at 49 sites in 16 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Schizophrenia is a chronic psychiatric illness with periods of remission and relapse. Patients vary in the frequency and severity of relapse, time until relapse and time in remission. Discontinuation of antipsychotic medication is by far the most important reason for relapse. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Schizophrenia
What is being tested?
Aripiprazole, Aripiprazole depot and Paliperidone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
536 participants
Where
49 sitesin 16 countries
Study dates
Feb 2015to 26 Aug 2020
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of schizophrenia as defined by DSM-IV-R (Diagnostic and Statistical Manual) as determined by the M.I.N.I.plus
  • Age 18 or older.
  • 3. The first psychosis occurred at least 6 months and no more than 7 years ago.*
  • If patients are using an antipsychotic drug, a medication switch is currently under consideration.
  • Capable of providing written informed consent
  • Time of first psychosis is defined as the first contact with a health care professional in relation to psychotic symptoms.

Who cannot join

  • Intolerance / hypersensitivity to both* of the drugs (including active substances, metabolites and excipients) in this study including oral paliperidone and aripiprazole and/or hypersensitivity to risperidone.
  • Pregnancy or lactation.
  • Patients who are currently using clozapine.
  • Patients who do not fully comprehend the purpose or are not competent to make a rational decision whether or not to participate.
  • Patients with a documented history of intolerance to both* of the study medications and/or a documented history of non-response to a treatment with both* study drugs of at least 6 weeks within the registered dose range.7. Patients who have been treated with an investigational drug within 30 days prior to screening.
  • 8. Simultaneous participation in another intervention study (neither medication or psychosocial intervention).
  • If intolerance/hypersensitivity or non-response in the past to one of the compounds is documented, the patient can still participate; however, randomization will take place by blocking that specific compound. That is, the patient will be randomized on either the oral or the depot arm of the other compound. This procedure of blocking one compound is also accepted for patients who have experienced too many side effects to one of the compounds in the past, as documented in the patient's medical record. The decision to block that specific compound for randomization in these cases is up to the discretion of the treating physician who will carefully balance this decision and clearly document it in the medical record.

Trial locations and contacts

49 sites in 16 countries.

49 sites in 16 countries

United Kingdom8 sites

  • Edmund Ward, St Martins Hospital Littlebourne Road Canterbury

    Kent

  • West London Mental Health Trust. East Recovery Team

    London, Avenue House 43-47 Avenue Road, W38NJ

  • Imperial College, Centre for Mental Health, Faculty of Medicine,

    London

  • Greater Manchester West Mental Health NHS Foundation Trust

    Manchester, Crowell House, Cromwell Road

  • Tees, Ask and Wearvalleys

    Middlesbrough

  • Northumberland

    Newcastle

  • Oxford Health NHS Foundation Trust

    Oxford

  • Surrey and Borders Partnership NHS Foundation Trust

    Surrey

Other trials in United Kingdom

Israel6 sites

  • Abravanel Mental Health Center

    Bat Yam

  • Be'er-Ness Mental Health Center

    Be’er Ya‘aqov

  • The Jerusalem Mental Health Center

    Jerusalem

  • Lev-Hasharon Medical Center for Mental Health

    Pardesiyya

  • Geha Medical Health Center

    Petah Tikva

  • The Chaim Sheba Medical Center

    Tel HaShomer, 52621

Other trials in Israel

Romania6 sites

  • Spitalul Clinic Judetean de Urgenta Arad - Clinica de Psihiatrie

    Arad

  • Spitalul Clinic de Psihiatrie "Prof. Dr. Alexandru Obregia"

    Bucharest

  • Spitalul Clinic de Psihiatrie "Prof. Dr. Alexandru Obregia

    Bucharest

  • Spitalul de Psihiatrie si pentru Masuri de Siguranta, Sapoca, Buzau

    Buzău

  • Spitalul Clinic de Neuropsihiatrie Craiova

    Craiova

  • Sitalul Clinic Judetean Mures

    Targu Mureş

Other trials in Romania

Germany4 sites

  • Klinik und Poliklinik für Psychiatrie und Psychotherapie der Heinrich-Heine-Universität

    Düsseldorf, Bergische Landstraße 2, 40629

  • Klinik für Psychiatrie, Psychotherapie und Psychosomatik der Martin-Luther-Universität

    Halle, Julius-Kühn-Straße 7, 06112

  • Technische Universität München (TUM

    München, Ismaningerstrasse 22, 81675

  • Department of Psychiatry and Psychotherapy

    München, Nussbaumstrasse 7, 80336

Other trials in Germany

Spain4 sites

  • Hospital Clínic de Barcelona. Unidad de Esquizofrenia

    Barcelona, C/Villarroel, 170. Escalera12, Planta 0, 08036

  • Child and Adolescent Psychiatry Department. Hospital General Universitario Gregorio Marañón. Servicio Madrileño de Salud

    Madrid

  • Facultad de Medicina Center

    Oviedo, Julián Clavería S/n, 33006

  • Hospital Universitario Marqués de Valdecilla, Servicio de Psiquiatría

    Santander, Cantabria, 39011

Other trials in Spain

Czechia3 sites

  • Dr. Ustohal

    Brno

  • Psychiatrická klinika LF UK

    Hradec Králové, Fakultní Nemocnice, 500 05

  • Dr. Mohr

    Prague

Other trials in Czechia

Italy3 sites

  • Servizio Psichiatrico Universitario di Diagnosi e Cura. Presidio Ospedaliero "San Salvatore" Università degli Studi dell'Aquila.

    L’Aquila

  • Department of Psychiatry, University of Naples SUN

    Naples, Largo Madonna Delle Grazie 1, 80138

  • Università degli Studi di Torino. Dipartimento di Neuroscienze

    Turin, Sezione Di Psichiatriavia Cherasco, 11, 10126

Other trials in Italy

Norway3 sites

  • Helse Bergen HF Haukeland University Hospital, Division of Psychiatry

    Bergen, 5021

  • Stavanger University Hospital

    Stavanger

  • St Olavs Hospital avd Østmarka / INM NTNU

    Trondheim, 7441

Other trials in Norway

Austria2 sites

  • Department of Biological Psychiatry, Innsbruck University Clinics

    Innsbruck, Anichstrasse 35, A-6020

  • Psychosoziale Dienste

    Vienna, Modecenterstraße, 1030

Other trials in Austria

Belgium2 sites

  • ZNA, department of Psychiatry, locatie Stuivenberg

    Antwerp, Lange Beeldekensstraat 267, 2060

  • Psychiatrisch Ziekenhuis Duffel

    Antwerp, Stationsstraat 22C, 2570

Other trials in Belgium

Hungary2 sites

  • Dr. Csekey

    Balassagyarmat

  • Department of Psychiatry and Psychotherapy, Semmelweis University

    Budapest

Other trials in Hungary

Poland2 sites

  • II Klinika Psychiatrii Uniwersytet Medyczny w Lublinie

    Lublin, Ul. Głuska 1, 20-439

  • Instytut psychiatrii i neurologii

    Warsaw, Sobieskiego 9, 02-957

Other trials in Poland

Bulgaria1 site

  • University Hospital of Neurology and Psychiatry 'St. Naum' 1

    Sofia, Louben Roussev Str., 1113

Other trials in Bulgaria

Denmark1 site

  • Center for Neuropsychiatric Research

    Glostrup Municipality, Ndr. Ringvej, 2600

Other trials in Denmark

Greece1 site

  • National and Kapodistrian University of Athens Medical School, Eginition Hospital

    Athens

Other trials in Greece

Netherlands1 site

  • University Medical Center

    Utrecht

Other trials in Netherlands

About this study

Schizophrenia is a chronic psychiatric illness with periods of remission and relapse. Patients vary in the frequency and severity of relapse, time until relapse and time in remission. Discontinuation of antipsychotic medication is by far the most important reason for relapse. A possible method to optimize medication adherence is to treat patients with long-term, depot medication rather than oral medication. However, despite its apparent "common sense" this approach has neither been universally accepted by practicing psychiatrists nor unequivocally demonstrated in clinical trials. Therefore, in this study we aim to investigate possible advantages of depot medication over oral antipsychotics in an independently designed and conducted, randomized, pragmatic trial.

Read the detailed description

It remains unclear if depot medication can reduce relapse rates and improve clinical outcome when offered to all patients in need of continuation treatment with antipsychotics. Before we can conclude whether or not all schizophrenia patients could benefit from a switch to depot formulations, several questions remain to be answered. Is depot medication associated with better continuation rates and outcome? How are depot medications tolerated as compared to oral medication? In order to clarify these important issues we aim to perform a large multi-center trial in which schizophrenia patients in need of continuous treatment who are randomized 1:1:1:1 to two different depot preparations or to two different oral medications.

In this pragmatic, randomized, open label, multicenter, multinational comparative trial, schizophrenic patients aged 18 years or older, having experienced the first psychosis between 6 months and 7 years ago,with an indication (patient or physician initiated) to receive medication or to switch to another antipsychotic drug, will enter the study.

The study duration will be one month for the medication switch and then a follow-up of 18 months. Patients having refused to take part in the study will be asked to give consent and participate in a naturalistic follow-up, during which they will be followed with the Clinical Global Impression list (CGI) as closely related to the study schedule as possible, unless they also refuse this.

Conditions
Schizophrenia
Being tested
Aripiprazole, Aripiprazole depot, Paliperidone, Paliperidone palmitate
Keywords
depot, oral, antipsychotics, paliperidone, aripiprazole
Medical subject headings
Schizophrenia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AripiprazoleDrug

    Also called Abilify

    Administration in once-a-day schedule without regard to meals.

  • Aripiprazole depotDrug

    Also called Abilify maintena

    Abilify Maintena is an intramuscular (IM) depot formulation of oral aripiprazole. It provides the efficacy and safety profile of oral aripiprazole in a once-monthly injection.

  • PaliperidoneDrug

    Also called Invega

    Administration once a day orally standardised in relation to food intake.

  • Paliperidone palmitateDrug

    Also called Xeplion

    In selected patients with schizophrenia and previous responsiveness to oral paliperidone or risperidone, Xeplion may be used without prior stabilization with oral treatment if psychotic symptoms are mild to moderate and a long-acting injectable is needed.

Study groups in NCT02146547
Study groupRoleWhat they receive
aripiprazole oralActive comparatorthe recommended starting dose for aripiprazole is 10 or 15 mg/day with a maintenance dose of 15 mg/day administered on a once-a-day schedule without regard to meals.Aripiprazole is effective in a dose range of 10 to 30 mg/day.
Receives: Drug: Aripiprazole
Aripiprazole depotActive comparatorThe recommended starting and maintenance dose of aripiprazole depot is 400 mg. Titration of the dose of this medicinal product is not required. It should be administered once monthly as a single injection (no sooner than 26 days after the previous injection). After the first injection, treatment with 10 mg to 20 mg oral aripiprazole should be continued for 14 consecutive days to maintain therapeutic aripiprazole concentrations during initiation of therapy. If there are adverse reactions with the 400 mg dosage, reduction of the dose to 300 mg once monthly should be considered.
Receives: Drug: Aripiprazole depot
PaliperidoneActive comparatorThe recommended dose of paliperidone for the treatment of schizophrenia is 6 mg once daily, administered in the morning. Initial dose titration is not required. Some patients may benefit from lower or higher doses within the recommended range of 3 mg to 12 mg once daily. Dosage adjustment, if indicated, should occur only after clinical reassessment. When dose increases are indicated, increments of 3 mg/day are recommended and generally should occur at intervals of more than 5 days.
Receives: Drug: Paliperidone
Paliperidone palmitateActive comparatorThe first two administrations of paliperidone palmitate (150 mg at visit 3 and 100 mg one week later) need to be administered deep into the deltoid muscle in order to attain therapeutic concentrations rapidly. No oral supplementation with paliperidone is needed. Following the second dose, monthly maintenance doses can be administered in either the deltoid or gluteal muscle. The recommended monthly maintenance dose is 75 mg, although some patients may benefit from lower doses within the recommended range of 25 to 150 mg based on individual patient tolerability and/or efficacy.
Receives: Drug: Paliperidone palmitate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. All cause discontinuation rates

    Compare all cause discontinuation rates in patients with schizophrenia randomized to oral antipsychotic medications (i.e., aripiprazole or paliperidone) versus depot antipsychotic medications (i.e., paliperidone palmitate or aripiprazole depot).

    Discontinuation consist of (multiple options are possible):

    • the allocated treatment is stopped or used at doses outside the allowed range.
    • medication is switched or augmented with another antipsychotic after visit 4 for more than 1 month continuously or for more than 3 months cumulative over the 18 months of the trial.
    • a patient misses a monthly visit and does not show up after reminding him
    • patient withdraws consent for the study.
    • clinician decision to withdraw the patient.

    Measured: 18 months

Secondary outcomes (7)

  1. Subjective Wellbeing under Neuroleptics

    Change from baseline in Subjective Wellbeing under Neuroleptics

    Measured: 18 months

  2. EuroQoL quality of life scale

    Change from baseline in EuroQoL quality of life scale

    Measured: 18 months

  3. Side effects assessment

    Change from baseline in SMARTS (Systematic Monitoring of Adverse events Related to TreatmentS) and the Abnormal and Involuntary Movement Scale.

    Measured: 18 months

  4. Assessment of cognitive functioning

    Compare the combined oral medication group with the combined depot treatment arms regarding cognitive functioning

    Measured: 18 months

  5. Assessment of Positive and Negative Symptom Scale

    Compare the combined oral medication group with the combined depot treatment arms regarding changes in different dimensions of psychopathology of schizophrenia

    Measured: 18 months

  6. Assessment of Personal and Social Performance Scale

    Compare the combined oral medication group with the combined depot

    Measured: 18 months

  7. Change from baseline of Personal and Social Performance Scale

    Compare the combined oral medication group with the combined depot

    Measured: Baseline until 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 May 2014 (estimated)
  2. Study startFeb 2015
  3. Primary completion26 Aug 2020
  4. Study completion26 Aug 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
536 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02146547
Sponsor's protocol ID
ABR49490
Acronym
EULAST
Status last verified
Aug 2020
First submitted
21 May 2014
Last updated
1 Sep 2020
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Mortazavi M, Aminifarsani Z, Rossum IW, Kahn RS, Fleischhacker WW, Davidson M, Weiser M, Siskind D, Leucht S; EULAST Study Group; Hasan A, Wagner E. Impact of Long-Acting Injectable Versus Oral Antipsychotic Treatment on All-Cause Discontinuation Risk in People with Early Phase Schizophrenia and Comorbid Substance Use Disorder: A Secondary Analysis of the EULAST Randomized Trial. CNS Drugs. 2026 Jan;40(1):99-109. doi: 10.1007/s40263-025-01225-0. Epub 2025 Sep 11.

    PubMed 40932600

  • Winter-van Rossum I, Weiser M, Galderisi S, Leucht S, Bitter I, Glenthoj B, Hasan A, Luykx J, Kupchik M, Psota G, Rocca P, Stefanis N, Teitelbaum A, Bar Haim M, Leucht C, Kemmler G, Schurr T; EULAST Study Group; Davidson M, Kahn RS, Fleischhacker WW. Efficacy of oral versus long-acting antipsychotic treatment in patients with early-phase schizophrenia in Europe and Israel: a large-scale, open-label, randomised trial (EULAST). Lancet Psychiatry. 2023 Mar;10(3):197-208. doi: 10.1016/S2215-0366(23)00005-6. Epub 2023 Jan 27.

    PubMed 36716759

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Aripiprazole, Aripiprazole depot and Paliperidone in people with Schizophrenia, run by UMC Utrecht at 49 sites in 16 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 49 sites in United Kingdom, Israel, Romania, Germany, Spain and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

All cause discontinuation rates (time frame: 18 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02146547, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2020.

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