European Long-acting Antipsychotics in Schizophrenia Trial

NCT ID: NCT02146547

Last Updated: 2020-09-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 536 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-28
• Study Completion Date: 2020-08-26

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

aripiprazole oral

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.

Group Type: ACTIVE_COMPARATOR

Aripiprazole

Intervention Type: DRUG

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

Aripiprazole depot

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.

Group Type: ACTIVE_COMPARATOR

Aripiprazole depot

Intervention Type: 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.

Paliperidone

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.

Group Type: ACTIVE_COMPARATOR

Paliperidone

Intervention Type: DRUG

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

Paliperidone palmitate

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.

Group Type: ACTIVE_COMPARATOR

Paliperidone palmitate

Intervention Type: 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.

Interventions

Aripiprazole

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

Intervention Type: DRUG

Aripiprazole depot

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.

Intervention Type: DRUG

Paliperidone

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

Intervention Type: DRUG

Paliperidone palmitate

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.

Intervention Type: DRUG

Other Intervention Names

Abilify; Abilify maintena; Invega; Xeplion

Eligibility Criteria

Inclusion Criteria

1. Diagnosis of schizophrenia as defined by DSM-IV-R (Diagnostic and Statistical Manual) as determined by the M.I.N.I.plus

2. Age 18 or older.

3. 3. The first psychosis occurred at least 6 months and no more than 7 years ago.*

4. If patients are using an antipsychotic drug, a medication switch is currently under consideration.

5. 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.

Exclusion Criteria

1. 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.

2. Pregnancy or lactation.

3. Patients who are currently using clozapine.

4. Patients who do not fully comprehend the purpose or are not competent to make a rational decision whether or not to participate.

5. 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

UMC Utrecht

OTHER

Sponsor Role: lead

Responsible Party

Rene Kahn

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rene S Kahn, professor

Role: PRINCIPAL_INVESTIGATOR

UMC Utrecht

Wolfgang Fleischhacker, professor

Role: PRINCIPAL_INVESTIGATOR

Department of Biological Psychiatry, Innsbruck University Clinics

Michael Davidson, professor

Role: PRINCIPAL_INVESTIGATOR

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

Locations

Department of Biological Psychiatry, Innsbruck University Clinics

Innsbruck, Anichstrasse 35, Austria

Psychosoziale Dienste

Vienna, Modecenterstraße, Austria

ZNA, department of Psychiatry, locatie Stuivenberg

Antwerp, Lange Beeldekensstraat 267, Belgium

Psychiatrisch Ziekenhuis Duffel

Antwerp, Stationsstraat 22C, Belgium

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

Sofia, Louben Roussev Str., Bulgaria

Psychiatrická klinika LF UK

Hradec Králové, Fakultní Nemocnice, Czechia

Dr. Ustohal

Brno, , Czechia

Dr. Mohr

Prague, , Czechia

Center for Neuropsychiatric Research

Glostrup Municipality, Ndr. Ringvej, Denmark

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

Düsseldorf, Bergische Landstraße 2, Germany

Technische Universität München (TUM

München, Ismaningerstrasse 22, Germany

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

Halle, Julius-Kühn-Straße 7, Germany

Department of Psychiatry and Psychotherapy

München, Nussbaumstrasse 7, Germany

National and Kapodistrian University of Athens Medical School, Eginition Hospital

Athens, , Greece

Dr. Csekey

Balassagyarmat, , Hungary

Department of Psychiatry and Psychotherapy, Semmelweis University

Budapest, , Hungary

Abravanel Mental Health Center

Bat Yam, , Israel

Be'er-Ness Mental Health Center

Be’er Ya‘aqov, , Israel

The Jerusalem Mental Health Center

Jerusalem, , Israel

Lev-Hasharon Medical Center for Mental Health

Pardesiyya, , Israel

Geha Medical Health Center

Petah Tikva, , Israel

The Chaim Sheba Medical Center

Tel Litwinsky, , Israel

Department of Psychiatry, University of Naples SUN

Naples, Largo Madonna Delle Grazie 1, Italy

Università degli Studi di Torino. Dipartimento di Neuroscienze

Turin, Sezione Di Psichiatriavia Cherasco, 11, Italy

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

L’Aquila, , Italy

University Medical Center

Utrecht, , Netherlands

Helse Bergen HF Haukeland University Hospital, Division of Psychiatry

Bergen, , Norway

Stavanger University Hospital

Stavanger, , Norway

St Olavs Hospital avd Østmarka / INM NTNU

Trondheim, , Norway

Instytut psychiatrii i neurologii

Warsaw, Sobieskiego 9, Poland

II Klinika Psychiatrii Uniwersytet Medyczny w Lublinie

Lublin, Ul. Głuska 1, Poland

Spitalul Clinic Judetean de Urgenta Arad - Clinica de Psihiatrie

Arad, , Romania

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

Bucharest, , Romania

Spitalul Clinic de Psihiatrie "Prof. Dr. Alexandru Obregia

Bucharest, , Romania

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

Buzău, , Romania

Spitalul Clinic de Neuropsihiatrie Craiova

Craiova, , Romania

Sitalul Clinic Judetean Mures

Targu Mureş, , Romania

Hospital Clínic de Barcelona. Unidad de Esquizofrenia

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

Hospital Universitario Marqués de Valdecilla, Servicio de Psiquiatría

Santander, Cantabria, Spain

Facultad de Medicina Center

Oviedo, Julián Clavería S/n, Spain

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

Madrid, , Spain

West London Mental Health Trust. East Recovery Team

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

Greater Manchester West Mental Health NHS Foundation Trust

Manchester, Crowell House, Cromwell Road, United Kingdom

Edmund Ward, St Martins Hospital Littlebourne Road Canterbury

Kent, , United Kingdom

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

London, , United Kingdom

Tees, Ask and Wearvalleys

Middlesbrough, , United Kingdom

Northumberland

Newcastle, , United Kingdom

Oxford Health NHS Foundation Trust

Oxford, , United Kingdom

Surrey and Borders Partnership NHS Foundation Trust

Surrey, , United Kingdom

Countries

Austria; Belgium; Bulgaria; Czechia; Denmark; Germany; Greece; Hungary; Israel; Italy; Netherlands; Norway; Poland; Romania; Spain; United Kingdom

References

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. 2025 Sep 11. doi: 10.1007/s40263-025-01225-0. Online ahead of print.

Reference Type: DERIVED

PMID: 40932600 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36716759 (View on PubMed)

Other Identifiers

ABR49490

Identifier Type: -

Identifier Source: org_study_id