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EULAST: European Long-acting Antipsychotics in Schizophrenia Trial

Sponsor
UMC Utrecht (Other)
Overall Status
Completed
CT.gov ID
NCT02146547
Collaborator
(none)
536
Enrollment
49
Locations
4
Arms
66.8
Actual Duration (Months)
10.9
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 4

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
536 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
European Long-acting Antipsychotics in Schizophrenia Trial
Actual Study Start Date :
Feb 1, 2015
Actual Primary Completion Date :
Aug 26, 2020
Actual Study Completion Date :
Aug 26, 2020

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: 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.

Drug: Aripiprazole
Administration in once-a-day schedule without regard to meals.
Other Names:
  • Abilify

    		•
    Active Comparator: 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.

    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.
    Other Names:
  • Abilify maintena

    		•
    Active Comparator: 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.

    Drug: Paliperidone
    Administration once a day orally standardised in relation to food intake.
    Other Names:
  • Invega

    		•
    Active Comparator: 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.

    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.
    Other Names:
  • Xeplion

    		•

    Outcome Measures

    Primary Outcome Measures

    1. All cause discontinuation rates [18 months]

      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.

    Secondary Outcome Measures

    1. Subjective Wellbeing under Neuroleptics [18 months]

      Change from baseline in Subjective Wellbeing under Neuroleptics

    2. EuroQoL quality of life scale [18 months]

      Change from baseline in EuroQoL quality of life scale

    3. Side effects assessment [18 months]

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

    4. Assessment of cognitive functioning [18 months]

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

    5. Assessment of Positive and Negative Symptom Scale [18 months]

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

    6. Assessment of Personal and Social Performance Scale [18 months]

      Compare the combined oral medication group with the combined depot

    7. Change from baseline of Personal and Social Performance Scale [Baseline until 18 months]

      Compare the combined oral medication group with the combined depot

    Other Outcome Measures

    1. Comparison between depot arms and the oral treatment arms on the one side [18 months]

      The comparisons will also be made between the depot arms and the oral treatment arms on the one side and the patients who are followed up naturalistically.Depot arms are compared regarding augmentation with oral antipsychotics after visit 4.

    2. Treatment success regarding outcomes in patients who have not given consent for the main trial [up to 18 months]

      compare treatment success regarding the outcomes mentioned above to those achieved in a group of patients who did not agree to participate in the trial but could be followed up with the CGI.

    3. Compare side effects between combined oral medication groups & combined depot treatment [18 months]

      Compare side effects and general wellbeing under antipsychotic medication between the combined oral medication groups with the combined depot treatment arms.

    4. Immune parameters [18 months]

      Associations between immune parameters on the one hand, and primary as well as secondary outcome measures on the other.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

      1. 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.

    6. 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Department of Biological Psychiatry, Innsbruck University Clinics Innsbruck Anichstrasse 35 Austria A-6020
    2 Psychosoziale Dienste Vienna Modecenterstraße Austria 1030
    3 ZNA, department of Psychiatry, locatie Stuivenberg Antwerp Lange Beeldekensstraat 267 Belgium 2060
    4 Psychiatrisch Ziekenhuis Duffel Antwerp Stationsstraat 22C Belgium 2570
    5 University Hospital of Neurology and Psychiatry 'St. Naum' 1 Sofia Louben Roussev Str. Bulgaria 1113
    6 Psychiatrická klinika LF UK Hradec Králové Fakultní Nemocnice Czechia 500 05
    7 Dr. Ustohal Brno Czechia
    8 Dr. Mohr Praha Czechia
    9 Center for Neuropsychiatric Research Glostrup Ndr. Ringvej Denmark 2600
    10 Klinik und Poliklinik für Psychiatrie und Psychotherapie der Heinrich-Heine-Universität Düsseldorf Bergische Landstraße 2 Germany 40629
    11 Technische Universität München (TUM München, Ismaningerstrasse 22 Germany 81675
    12 Klinik für Psychiatrie, Psychotherapie und Psychosomatik der Martin-Luther-Universität Halle Julius-Kühn-Straße 7 Germany 06112
    13 Department of Psychiatry and Psychotherapy München Nussbaumstrasse 7 Germany 80336
    14 National and Kapodistrian University of Athens Medical School, Eginition Hospital Athens Greece
    15 Dr. Csekey Balassagyarmat Hungary
    16 Department of Psychiatry and Psychotherapy, Semmelweis University Budapest Hungary
    17 Abravanel Mental Health Center Bat-Yam Israel
    18 Be'er-Ness Mental Health Center Be'er Ya'aqov Israel
    19 The Jerusalem Mental Health Center Jerusalem Israel
    20 Lev-Hasharon Medical Center for Mental Health Pardesiyya Israel
    21 Geha Medical Health Center Petach-Tikva Israel
    22 The Chaim Sheba Medical Center Tel-Hashomer Israel 52621
    23 Department of Psychiatry, University of Naples SUN Naples Largo Madonna Delle Grazie 1 Italy 80138
    24 Università degli Studi di Torino. Dipartimento di Neuroscienze Turin Sezione Di Psichiatriavia Cherasco, 11 Italy 10126
    25 Servizio Psichiatrico Universitario di Diagnosi e Cura. Presidio Ospedaliero "San Salvatore" Università degli Studi dell'Aquila. L'Aquila Italy
    26 University Medical Center Utrecht Netherlands
    27 Helse Bergen HF Haukeland University Hospital, Division of Psychiatry Bergen Norway 5021
    28 Stavanger University Hospital Stavanger Norway
    29 St Olavs Hospital avd Østmarka / INM NTNU Trondheim Norway 7441
    30 Instytut psychiatrii i neurologii Warsaw Sobieskiego 9 Poland 02-957
    31 II Klinika Psychiatrii Uniwersytet Medyczny w Lublinie Lublin Ul. Głuska 1 Poland 20-439
    32 Spitalul Clinic Judetean de Urgenta Arad - Clinica de Psihiatrie Arad Romania
    33 Spitalul Clinic de Psihiatrie "Prof. Dr. Alexandru Obregia" Bucharest Romania
    34 Spitalul Clinic de Psihiatrie "Prof. Dr. Alexandru Obregia Bucharest Romania
    35 Spitalul de Psihiatrie si pentru Masuri de Siguranta, Sapoca, Buzau Buzău Romania
    36 Spitalul Clinic de Neuropsihiatrie Craiova Craiova Romania
    37 Sitalul Clinic Judetean Mures Targu Mureş Romania
    38 Hospital Clínic de Barcelona. Unidad de Esquizofrenia Barcelona C/Villarroel, 170. Escalera12, Planta 0 Spain 08036
    39 Hospital Universitario Marqués de Valdecilla, Servicio de Psiquiatría Santander Cantabria Spain 39011
    40 Facultad de Medicina Center Oviedo Julián Clavería S/n Spain 33006
    41 Child and Adolescent Psychiatry Department. Hospital General Universitario Gregorio Marañón. Servicio Madrileño de Salud Madrid Spain
    42 West London Mental Health Trust. East Recovery Team London Avenue House 43-47 Avenue Road United Kingdom W38NJ
    43 Greater Manchester West Mental Health NHS Foundation Trust Manchester Crowell House, Cromwell Road United Kingdom
    44 Edmund Ward, St Martins Hospital Littlebourne Road Canterbury Kent United Kingdom
    45 Imperial College, Centre for Mental Health, Faculty of Medicine, London United Kingdom
    46 Tees, Ask and Wearvalleys Middlesbrough United Kingdom
    47 Northumberland Newcastle United Kingdom
    48 Oxford Health NHS Foundation Trust Oxford United Kingdom
    49 Surrey and Borders Partnership NHS Foundation Trust Surrey United Kingdom

    Sponsors and Collaborators

    • UMC Utrecht

    Investigators

    • Principal Investigator: 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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Rene Kahn, Professor, UMC Utrecht
    ClinicalTrials.gov Identifier:
    NCT02146547
    Other Study ID Numbers:
    • ABR49490
    First Posted:
    May 26, 2014
    Last Update Posted:
    Sep 1, 2020
    Last Verified:
    Aug 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Rene Kahn, Professor, UMC Utrecht
    depot, oral, antipsychotics, paliperidone, aripiprazole
    Additional relevant MeSH terms:
    Schizophrenia
    Aripiprazole
    Paliperidone Palmitate

    Study Results

    No Results Posted as of Sep 1, 2020