European Long-acting Antipsychotics in Schizophrenia Trial (EULAST)

UMC Utrecht

Status and phase: Completed; Phase 4

Conditions: Schizophrenia

Treatments: Drug: Paliperidone palmitate; Drug: Paliperidone; Drug: Aripiprazole; Drug: Aripiprazole depot

Study type: Interventional

Funder types: Other

Identifiers

NCT02146547

ABR49490

Details and patient eligibility

About

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.

Full 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.

Enrollment: 536 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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536 participants in 4 patient groups

aripiprazole oral

Active Comparator group

Description:

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.

Treatment:

Drug: Aripiprazole

Aripiprazole depot

Active Comparator group

Description:

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.

Treatment:

Drug: Aripiprazole depot

Paliperidone

Active Comparator group

Description:

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.

Treatment:

Drug: Paliperidone

Paliperidone palmitate

Active Comparator group

Description:

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.

Treatment:

Drug: Paliperidone palmitate