Clinical trial NCT02146547: European Long-acting Antipsychotics in Schizophrenia Trial
Official title: European Long-acting Antipsychotics in Schizophrenia Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Schizophrenia
Keywords: depot, oral, antipsychotics, paliperidone, aripiprazole
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
First posted: 2014-05-26
Enrollment: 536
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: All cause discontinuation rates
timeFrame: 18 months
Secondary outcomes:
measure: Subjective Wellbeing under Neuroleptics
timeFrame: 18 months
measure: EuroQoL quality of life scale
timeFrame: 18 months
measure: Side effects assessment
timeFrame: 18 months
measure: Assessment of cognitive functioning
timeFrame: 18 months
measure: Assessment of Positive and Negative Symptom Scale
timeFrame: 18 months
measure: Assessment of Personal and Social Performance Scale
timeFrame: 18 months
measure: Change from baseline of Personal and Social Performance Scale
timeFrame: Baseline until 18 months
Other outcomes:
measure: Comparison between depot arms and the oral treatment arms on the one side
timeFrame: 18 months
measure: Treatment success regarding outcomes in patients who have not given consent for the main trial
timeFrame: up to 18 months
measure: Compare side effects between combined oral medication groups & combined depot treatment
timeFrame: 18 months
measure: Immune parameters
timeFrame: 18 months
Locations:
city: Innsbruck
country: Austria
facility: Department of Biological Psychiatry, Innsbruck University Clinics
state: Anichstrasse 35
city: Vienna
country: Austria
facility: Psychosoziale Dienste
state: Modecenterstraße
city: Antwerp
country: Belgium
facility: ZNA, department of Psychiatry, locatie Stuivenberg
state: Lange Beeldekensstraat 267
city: Antwerp
country: Belgium
facility: Psychiatrisch Ziekenhuis Duffel
state: Stationsstraat 22C
city: Sofia
country: Bulgaria
facility: University Hospital of Neurology and Psychiatry 'St. Naum' 1
state: Louben Roussev Str.
city: Hradec Králové
country: Czechia
facility: Psychiatrická klinika LF UK
state: Fakultní Nemocnice
city: Brno
country: Czechia
facility: Dr. Ustohal
city: Praha
country: Czechia
facility: Dr. Mohr
city: Glostrup
country: Denmark
facility: Center for Neuropsychiatric Research
state: Ndr. Ringvej
city: Düsseldorf
country: Germany
facility: Klinik und Poliklinik für Psychiatrie und Psychotherapie der Heinrich-Heine-Universität
state: Bergische Landstraße 2
city: München,
country: Germany
facility: Technische Universität München (TUM
state: Ismaningerstrasse 22
city: Halle
country: Germany
facility: Klinik für Psychiatrie, Psychotherapie und Psychosomatik der Martin-Luther-Universität
state: Julius-Kühn-Straße 7
city: München
country: Germany
facility: Department of Psychiatry and Psychotherapy
state: Nussbaumstrasse 7
city: Athens
country: Greece
facility: National and Kapodistrian University of Athens Medical School, Eginition Hospital
city: Balassagyarmat
country: Hungary
facility: Dr. Csekey
city: Budapest
country: Hungary
facility: Department of Psychiatry and Psychotherapy, Semmelweis University
city: Bat-Yam
country: Israel
facility: Abravanel Mental Health Center
city: Be'er Ya'aqov
country: Israel
facility: Be'er-Ness Mental Health Center
city: Jerusalem
country: Israel
facility: The Jerusalem Mental Health Center
city: Pardesiyya
country: Israel
facility: Lev-Hasharon Medical Center for Mental Health
city: Petach-Tikva
country: Israel
facility: Geha Medical Health Center
city: Tel-Hashomer
country: Israel
facility: The Chaim Sheba Medical Center
city: Naples
country: Italy
facility: Department of Psychiatry, University of Naples SUN
state: Largo Madonna Delle Grazie 1
city: Turin
country: Italy
facility: Università degli Studi di Torino. Dipartimento di Neuroscienze
state: Sezione Di Psichiatriavia Cherasco, 11
city: L'Aquila
country: Italy
facility: Servizio Psichiatrico Universitario di Diagnosi e Cura. Presidio Ospedaliero "San Salvatore" Università degli Studi dell'Aquila.
city: Utrecht
country: Netherlands
facility: University Medical Center
city: Bergen
country: Norway
facility: Helse Bergen HF Haukeland University Hospital, Division of Psychiatry
city: Stavanger
country: Norway
facility: Stavanger University Hospital
city: Trondheim
country: Norway
facility: St Olavs Hospital avd Østmarka / INM NTNU
city: Warsaw
country: Poland
facility: Instytut psychiatrii i neurologii
state: Sobieskiego 9
city: Lublin
country: Poland
facility: II Klinika Psychiatrii Uniwersytet Medyczny w Lublinie
state: Ul. Głuska 1
city: Arad
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Arad - Clinica de Psihiatrie
city: Bucharest
country: Romania
facility: Spitalul Clinic de Psihiatrie "Prof. Dr. Alexandru Obregia"
city: Bucharest
country: Romania
facility: Spitalul Clinic de Psihiatrie "Prof. Dr. Alexandru Obregia
city: Buzău
country: Romania
facility: Spitalul de Psihiatrie si pentru Masuri de Siguranta, Sapoca, Buzau
city: Craiova
country: Romania
facility: Spitalul Clinic de Neuropsihiatrie Craiova
city: Targu Mureş
country: Romania
facility: Sitalul Clinic Judetean Mures
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona. Unidad de Esquizofrenia
state: C/Villarroel, 170. Escalera12, Planta 0
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla, Servicio de Psiquiatría
state: Cantabria
city: Oviedo
country: Spain
facility: Facultad de Medicina Center
state: Julián Clavería S/n
city: Madrid
country: Spain
facility: Child and Adolescent Psychiatry Department. Hospital General Universitario Gregorio Marañón. Servicio Madrileño de Salud
city: London
country: United Kingdom
facility: West London Mental Health Trust. East Recovery Team
state: Avenue House 43-47 Avenue Road
city: Manchester
country: United Kingdom
facility: Greater Manchester West Mental Health NHS Foundation Trust
state: Crowell House, Cromwell Road
city: Kent
country: United Kingdom
facility: Edmund Ward, St Martins Hospital Littlebourne Road Canterbury
city: London
country: United Kingdom
facility: Imperial College, Centre for Mental Health, Faculty of Medicine,
city: Middlesbrough
country: United Kingdom
facility: Tees, Ask and Wearvalleys
city: Newcastle
country: United Kingdom
facility: Northumberland
city: Oxford
country: United Kingdom
facility: Oxford Health NHS Foundation Trust
city: Surrey
country: United Kingdom
facility: Surrey and Borders Partnership NHS Foundation Trust
Study officials:
affiliation: UMC Utrecht
name: Rene S Kahn, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Biological Psychiatry, Innsbruck University Clinics
name: Wolfgang Fleischhacker, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Psychiatry, Sackler Faculty of Medicine, Tel Aviv University, Israel
name: Michael Davidson, professor
role: PRINCIPAL_INVESTIGATOR
References: