European Long-acting Antipsychotics in Schizophrenia Trial

NCT02146547 | Completed Phase 4 DMC

• 1 other identifier: ABR49490
• Study Type: interventional
• Target: 536
• Locations: 16 countries
• Sites: 49

Brief 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. 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.

Conditions

Schizophrenia

Keywords

depot, oral, antipsychotics, paliperidone, aripiprazole

Outcome Measures

Primary Outcomes (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.

  18 months

Secondary Outcomes (7)

• Subjective Wellbeing under Neuroleptics

  18 months

• EuroQoL quality of life scale

  18 months

• Side effects assessment

  18 months

• Assessment of cognitive functioning

  18 months

• Assessment of Positive and Negative Symptom Scale

  18 months

Other Outcomes (4)

• Comparison between depot arms and the oral treatment arms on the one side

  18 months

• Treatment success regarding outcomes in patients who have not given consent for the main trial

  up to 18 months

• Compare side effects between combined oral medication groups & combined depot treatment

  18 months

Study Arms (4)

aripiprazole oral

ACTIVE COMPARATOR

the 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.

Drug: Aripiprazole

Aripiprazole depot

ACTIVE COMPARATOR

The 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.

Drug: Aripiprazole depot

Paliperidone

ACTIVE COMPARATOR

The 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.

Drug: Paliperidone

Paliperidone palmitate

ACTIVE COMPARATOR

The 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.

Drug: Paliperidone palmitate

Interventions

Aripiprazole DRUG

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

Also known as: Abilify

aripiprazole oral

Aripiprazole depot DRUG

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.

Also known as: Abilify maintena

Aripiprazole depot

Paliperidone DRUG

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

Also known as: Invega

Paliperidone

Paliperidone palmitate DRUG

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.

Also known as: Xeplion

Paliperidone palmitate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• \. 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.

You may not qualify if:

• 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.
• \. 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.

Sponsors & Collaborators

• UMC Utrecht: lead

Study Sites (49)

Department of Biological Psychiatry, Innsbruck University Clinics

Innsbruck, Anichstrasse 35, A-6020, Austria

Location

Psychosoziale Dienste

Vienna, Modecenterstraße, 1030, Austria

Location

ZNA, department of Psychiatry, locatie Stuivenberg

Antwerp, Lange Beeldekensstraat 267, 2060, Belgium

Location

Psychiatrisch Ziekenhuis Duffel

Antwerp, Stationsstraat 22C, 2570, Belgium

Location

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

Sofia, Louben Roussev Str., 1113, Bulgaria

Location

Psychiatrická klinika LF UK

Hradec Králové, Fakultní Nemocnice, 500 05, Czechia

Location

Dr. Ustohal

Brno, Czechia

Location

Dr. Mohr

Prague, Czechia

Location

Center for Neuropsychiatric Research

Glostrup Municipality, Ndr. Ringvej, 2600, Denmark

Location

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

Düsseldorf, Bergische Landstraße 2, 40629, Germany

Location

Technische Universität München (TUM

München, Ismaningerstrasse 22, 81675, Germany

Location

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

Halle, Julius-Kühn-Straße 7, 06112, Germany

Location

Department of Psychiatry and Psychotherapy

München, Nussbaumstrasse 7, 80336, Germany

Location

National and Kapodistrian University of Athens Medical School, Eginition Hospital

Athens, Greece

Location

Dr. Csekey

Balassagyarmat, Hungary

Location

Department of Psychiatry and Psychotherapy, Semmelweis University

Budapest, Hungary

Location

Abravanel Mental Health Center

Bat Yam, Israel

Location

Be'er-Ness Mental Health Center

Be’er Ya‘aqov, Israel

Location

The Jerusalem Mental Health Center

Jerusalem, Israel

Location

Lev-Hasharon Medical Center for Mental Health

Pardesiyya, Israel

Location

Geha Medical Health Center

Petah Tikva, Israel

Location

The Chaim Sheba Medical Center

Tel Litwinsky, 52621, Israel

Location

Department of Psychiatry, University of Naples SUN

Naples, Largo Madonna Delle Grazie 1, 80138, Italy

Location

Università degli Studi di Torino. Dipartimento di Neuroscienze

Turin, Sezione Di Psichiatriavia Cherasco, 11, 10126, Italy

Location

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

L’Aquila, Italy

Location

University Medical Center

Utrecht, Netherlands

Location

Helse Bergen HF Haukeland University Hospital, Division of Psychiatry

Bergen, 5021, Norway

Location

Stavanger University Hospital

Stavanger, Norway

Location

St Olavs Hospital avd Østmarka / INM NTNU

Trondheim, 7441, Norway

Location

Instytut psychiatrii i neurologii

Warsaw, Sobieskiego 9, 02-957, Poland

Location

II Klinika Psychiatrii Uniwersytet Medyczny w Lublinie

Lublin, Ul. Głuska 1, 20-439, Poland

Location

Spitalul Clinic Judetean de Urgenta Arad - Clinica de Psihiatrie

Arad, Romania

Location

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

Bucharest, Romania

Location

Spitalul Clinic de Psihiatrie "Prof. Dr. Alexandru Obregia

Bucharest, Romania

Location

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

Buzău, Romania

Location

Spitalul Clinic de Neuropsihiatrie Craiova

Craiova, Romania

Location

Sitalul Clinic Judetean Mures

Targu Mureş, Romania

Location

Hospital Clínic de Barcelona. Unidad de Esquizofrenia

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

Location

Hospital Universitario Marqués de Valdecilla, Servicio de Psiquiatría

Santander, Cantabria, 39011, Spain

Location

Facultad de Medicina Center

Oviedo, Julián Clavería S/n, 33006, Spain

Location

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

Madrid, Spain

Location

West London Mental Health Trust. East Recovery Team

London, Avenue House 43-47 Avenue Road, W38NJ, United Kingdom

Location

Greater Manchester West Mental Health NHS Foundation Trust

Manchester, Crowell House, Cromwell Road, United Kingdom

Location

Edmund Ward, St Martins Hospital Littlebourne Road Canterbury

Kent, United Kingdom

Location

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

London, United Kingdom

Location

Tees, Ask and Wearvalleys

Middlesbrough, United Kingdom

Location

Northumberland

Newcastle, United Kingdom

Location

Oxford Health NHS Foundation Trust

Oxford, United Kingdom

Location

Surrey and Borders Partnership NHS Foundation Trust

Surrey, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 40932600 DERIVED

• 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.

  PMID: 36716759 DERIVED

MeSH Terms

Conditions

Schizophrenia

Interventions

Aripiprazole; Paliperidone Palmitate

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Isoxazoles; Azoles; Pyrimidines

Study Officials

• Rene S Kahn, professor

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

• Wolfgang Fleischhacker, professor

  Department of Biological Psychiatry, Innsbruck University Clinics

  PRINCIPAL INVESTIGATOR

• Michael Davidson, professor

  Department of Psychiatry, Sackler Faculty of Medicine, Tel Aviv University, Israel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 21, 2014
• First Posted: May 26, 2014
• Study Start: February 1, 2015
• Primary Completion: August 26, 2020
• Study Completion: August 26, 2020
• Last Updated: September 1, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

BU (1); BE (2); DK (1); RO (6); GB (8); AU (2); CZ (3); NO (3); ES (4); HU (2); IL (6); DE (4); GR (1); IT (3); PL (2); NL (1)