European Long-acting Antipsychotics in Schizophrenia Trial

Schizophrenia Clinical Trial

— EULAST  

Official title:

European Long-acting Antipsychotics in Schizophrenia Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02146547
• Other study ID #: ABR49490
• Status: Completed
• Phase: Phase 4
• Start date: February 2015
• Est. completion date: August 26, 2020

Study information

• Verified date: August 2020
• Source: UMC Utrecht
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 536
• Est. completion date: August 26, 2020
• Est. primary completion date: August 26, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• Aripiprazole
Administration in once-a-day schedule without regard to meals.
• 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.
• Paliperidone
Administration once a day orally standardised in relation to food intake.
• 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.

Locations

Country	Name	City	State
Austria	Department of Biological Psychiatry, Innsbruck University Clinics	Innsbruck	Anichstrasse 35
Austria	Psychosoziale Dienste	Vienna	Modecenterstraße
Belgium	Psychiatrisch Ziekenhuis Duffel	Antwerp	Stationsstraat 22C
Belgium	ZNA, department of Psychiatry, locatie Stuivenberg	Antwerp	Lange Beeldekensstraat 267
Bulgaria	University Hospital of Neurology and Psychiatry 'St. Naum' 1	Sofia	Louben Roussev Str.
Czechia	Dr. Ustohal	Brno
Czechia	Psychiatrická klinika LF UK	Hradec Králové	Fakultní Nemocnice
Czechia	Dr. Mohr	Praha
Denmark	Center for Neuropsychiatric Research	Glostrup	Ndr. Ringvej
Germany	Klinik und Poliklinik für Psychiatrie und Psychotherapie der Heinrich-Heine-Universität	Düsseldorf	Bergische Landstraße 2
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	Technische Universität München (TUM	München,	Ismaningerstrasse 22
Greece	National and Kapodistrian University of Athens Medical School, Eginition Hospital	Athens
Hungary	Dr. Csekey	Balassagyarmat
Hungary	Department of Psychiatry and Psychotherapy, Semmelweis University	Budapest
Israel	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	Petach-Tikva
Israel	The Chaim Sheba Medical Center	Tel-Hashomer
Italy	Servizio Psichiatrico Universitario di Diagnosi e Cura. Presidio Ospedaliero "San Salvatore" Università degli Studi dell'Aquila.	L'Aquila
Italy	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
Netherlands	University Medical Center	Utrecht
Norway	Helse Bergen HF Haukeland University Hospital, Division of Psychiatry	Bergen
Norway	Stavanger University Hospital	Stavanger
Norway	St Olavs Hospital avd Østmarka / INM NTNU	Trondheim
Poland	II Klinika Psychiatrii Uniwersytet Medyczny w Lublinie	Lublin	Ul. Gluska 1
Poland	Instytut psychiatrii i neurologii	Warsaw	Sobieskiego 9
Romania	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	Buzau
Romania	Spitalul Clinic de Neuropsihiatrie Craiova	Craiova
Romania	Sitalul Clinic Judetean Mures	Targu Mures
Spain	Hospital Clínic de Barcelona. Unidad de Esquizofrenia	Barcelona	C/Villarroel, 170. Escalera12, Planta 0
Spain	Child and Adolescent Psychiatry Department. Hospital General Universitario Gregorio Marañón. Servicio Madrileño de Salud	Madrid
Spain	Facultad de Medicina Center	Oviedo	Julián Clavería S/n
Spain	Hospital Universitario Marqués de Valdecilla, Servicio de Psiquiatría	Santander	Cantabria
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	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	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

Sponsors (1)

Lead Sponsor	Collaborator
UMC Utrecht

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Comparison between depot arms and the oral treatment arms on the one side	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.	18 months
Other	Treatment success regarding outcomes in patients who have not given consent for the main trial	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.	up to 18 months
Other	Compare side effects between combined oral medication groups & combined depot treatment	Compare side effects and general wellbeing under antipsychotic medication between the combined oral medication groups with the combined depot treatment arms.	18 months
Other	Immune parameters	Associations between immune parameters on the one hand, and primary as well as secondary outcome measures on the other.	18 months
Primary	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	Subjective Wellbeing under Neuroleptics	Change from baseline in Subjective Wellbeing under Neuroleptics	18 months
Secondary	EuroQoL quality of life scale	Change from baseline in EuroQoL quality of life scale	18 months
Secondary	Side effects assessment	Change from baseline in SMARTS (Systematic Monitoring of Adverse events Related to TreatmentS) and the Abnormal and Involuntary Movement Scale.	18 months
Secondary	Assessment of cognitive functioning	Compare the combined oral medication group with the combined depot treatment arms regarding cognitive functioning	18 months
Secondary	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	18 months
Secondary	Assessment of Personal and Social Performance Scale	Compare the combined oral medication group with the combined depot	18 months
Secondary	Change from baseline of Personal and Social Performance Scale	Compare the combined oral medication group with the combined depot	Baseline until 18 months