European Long-acting Antipsychotics in Schizophrenia Trial (EULAST)
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|ClinicalTrials.gov Identifier: NCT02146547|
Recruitment Status : Active, not recruiting
First Posted : May 26, 2014
Last Update Posted : January 16, 2019
|Condition or disease||Intervention/treatment||Phase|
|Schizophrenia||Drug: Aripiprazole Drug: Aripiprazole depot Drug: Paliperidone Drug: Paliperidone palmitate||Phase 4|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||536 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||European Long-acting Antipsychotics in Schizophrenia Trial|
|Actual Study Start Date :||February 2015|
|Estimated Primary Completion Date :||August 2020|
|Estimated Study Completion Date :||September 2020|
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.
Administration in once-a-day schedule without regard to meals.
Other Name: 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 Name: 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.
Administration once a day orally standardised in relation to food intake.
Other Name: 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 Name: Xeplion
- All cause discontinuation rates [ Time Frame: 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.
- Subjective Wellbeing under Neuroleptics [ Time Frame: 18 months ]Change from baseline in Subjective Wellbeing under Neuroleptics
- EuroQoL quality of life scale [ Time Frame: 18 months ]Change from baseline in EuroQoL quality of life scale
- Side effects assessment [ Time Frame: 18 months ]Change from baseline in SMARTS (Systematic Monitoring of Adverse events Related to TreatmentS) and the Abnormal and Involuntary Movement Scale.
- Assessment of cognitive functioning [ Time Frame: 18 months ]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 ]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 ]Compare the combined oral medication group with the combined depot
- Change from baseline of Personal and Social Performance Scale [ Time Frame: Baseline until 18 months ]Compare the combined oral medication group with the combined depot
- Comparison between depot arms and the oral treatment arms on the one side [ Time Frame: 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.
- Treatment success regarding outcomes in patients who have not given consent for the main trial [ Time Frame: 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.
- Compare side effects between combined oral medication groups & combined depot treatment [ Time Frame: 18 months ]Compare side effects and general wellbeing under antipsychotic medication between the combined oral medication groups with the combined depot treatment arms.
- Immune parameters [ Time Frame: 18 months ]Associations between immune parameters on the one hand, and primary as well as secondary outcome measures on the other.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02146547
|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|