Trial document




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  DRKS00007568

Trial Description

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Title

European Long-acting Antipsychotics in Schizophrenia Trial

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Trial Acronym

EULAST

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URL of the Trial

http://www.eulast.eu

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Brief Summary in Lay Language

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.

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Brief Summary in Scientific Language

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 6 months up to seven 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.

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Organizational Data

  •   DRKS00007568
  •   2015/06/18
  •   2014/05/21
  •   yes
  •   Approved
  •   427/14, Ethik-Kommission der Fakultät für Medizin der Technischen Universität München
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Secondary IDs

  •   2014-002765-30 
  •   NCT02146547  (ClinicalTrials.gov)
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Health Condition or Problem studied

  •   F20 -  Schizophrenia
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Interventions/Observational Groups

  •   in the first month taper-off, discontinuation of pre-study antipsychotic and and increase of study medication to optimal dose, for further 18 months Abilify (aripiprazole), 10 or 15 mg/day p.o. (tablet) with a maintenance dose of 15 mg/day

  •   in the first month discontinuation of pre-study antipsychotic and treatment with Aripiprazole p.o. (tablet).
    then for further 18 months Abilify depot (aripiprazole), 400 mg i.m. once per month 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.
  •   in the first month taper-off, discontinuation of pre-study antipsychotic and treatment with Paliperidone p.o. (tablet);
    for further 18 months Invega (Paliperidone), 6 mg/d p.o. (extended-release tablet) once daily, administered in the morning. No titration required, recommended range 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.
  •   in the first month discontinuation of pre-study antipsychotic and treatment with Paliperidone p.o.(tablet);
    for further 18 months Xeplion (Paliperidon palmitat depot), maintenance dose 75 mg i.m. monthly (suspension) in the deltoid or gluteal muscle. Recommended dose range 25 to 150 mg based on individual patient tolerability and efficacy. 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.
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Open (masking not used)
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  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   IV
  •   No
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Primary Outcome

All cause discontinuation rates [ Time Frame: 18 months ] [ Designated as safety issue: No ]

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.

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Secondary Outcome

Subjective Wellbeing under Neuroleptics [ Time Frame: 18 months; week 0 and 8, after 3, 4, 5, 9,13, 16 and 19 months and at all cause discontinuation visit] [Designated as safety issue: No ]
Change from baseline in Subjective Wellbeing under Neuroleptics [PLEASE NOTE: BASELINE IS DEFINED AS VISIT 4 AT WEEK 8, SO ALL SCALES AND EXAMINATIONS FOR WHICH THE ENDPOINT IS "CHANGE FROM BASELINE" REFERS TO THE BASELINE VISIT 4 AT WEEK 8]
EuroQoL quality of life scale [Time frame 18 months; week 0 and 8, after 3, 4, 5, 9, 13, 16 and 19 months and at all cause discontinuation visit] [Designated as safety issue: No ]
Change from baseline in EuroQoL quality of life scale
Side effects assessment [Time Frame: 18 months, at screening, week 0, 4 and 8, then once monthly at each visit for 17 months and at all cause discontinuation visit] [Designated as safety issue: Yes ]
Change from baseline in SMARTS (Systematic Monitoring of Adverse events Related to TreatmentS) and the AIMS (Abnormal and Involuntary Movement Scale), at week 0, 4 (only SMARTS) and 8, after 3, 4, 5, 9, 13, 16 and 19 months and at all cause discontinuation visit] .
Assessment of cognitive functioning [ Time Frame: 18 months, in week 8 and after 9 and 19 months and at all cause discontinuation visit] [Designated as safety issue: No ]
Compare the combined oral medication group with the combined depot treatment arms regarding cognitive functioning
Assessment of Positive and Negative Symptom Scale [Time Frame: 18 months; in week 0, 4, 8, after 3, 4, 5, 9, 13, 16 and 19 months and at all cause discontinuation visit] [ Designated as safety issue: No ]
Compare the combined oral medication group with the combined depot treatment arms regarding changes in different dimensions of psychopathology of schizophrenia
Assessment of Personal and Social Performance Scale [Time Frame: 18 months; in week 0 and 8, and after 3, 4, 5, 9, 13, 16 and 19 months and at all cause discontinuation visit] [ Designated as safety issue: No ]
Change from baseline of Personal and Social Performance Scale [ Time Frame: 18 months ] [ Designated as safety issue: No ]

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Countries of Recruitment

  •   Belgium
  •   Bulgaria
  •   Denmark
  •   Germany
  •   Greece
  •   United Kingdom
  •   Israel
  •   Italy
  •   Netherlands
  •   Norway
  •   Austria
  •   Poland
  •   Romania
  •   Spain
  •   Czech Republic
  •   Hungary
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Locations of Recruitment

  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
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Recruitment

  •   Actual
  •   2015/02/24
  •   520
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

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 six 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

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Exclusion Criteria

Intolerance / hypersensitivity to one of the drugs (including active substances, metabolites and excipients) in this study including oral risperidone, paliperidone and aripiprazole.
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 non-response and/or intolerance to any of the study medications.
Forensic patients.
Patients who have been treated with an investigational drug within 30 days prior to screening.

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Addresses

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    • Foundation European Group for Research in Schizophrenia (EGRIS)
    • Mr.  Professor  Rene  Kahn 
    • Retstraat 13
    • 6658 DB   BENEDEN-LEEUWEN
    • Netherlands
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    • Klinik für Psychiatrie und PsychotherapieKlinikum rechts der Isar der TU München
    • Mr.  Professor  Stefan  Leucht 
    • Ismaningerstrasse 22
    • 81675  München
    • Germany
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    • Klinik für Psychiatrie und PsychotherapieKlinikum rechts der Isar der TU München
    • Mr.  Professor  Stefan  Leucht 
    • Ismaningerstrasse 22
    • 81675  München
    • Germany
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Sources of Monetary or Material Support

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    • Foundation European Group for Research in Schizophrenia (EGRIS), Department of Psychiatry, University Medical Center Utrecht
    • Heidelberglaan 100
    • 3584 CX  Utrecht
    • Germany
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.