Effects of early clozapine treatment on remission rates in acute schizophrenia (EARLY)

Phase 1

Conditions: Schizophrenia
MedDRA version: 20.0Level: PTClassification code 10039626Term: SchizophreniaSystem Organ Class: 10037175 - Psychiatric disorders
Therapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]

Registration Number: EUCTR2018-001514-15-DE

Lead Sponsor: Bezirkskliniken Schwaben

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 220

Inclusion Criteria

1.Age 18 to 65 years
2.Signed informed consent
3.DSM-V diagnosis of schizophrenia confirmed by the Mini International Neuropsychiatric Interview
4.At least one documented prior hospitalization due to the illness in the medical history (the current hospitalization can be considered as ’prior’ hospitalization if its = 4 weeks) at screening
5.For treatment-naïve patients (defined as no previous antipsychotic treatment or a maximum of 30 days of treatment), an antipsychotic treatment attempt of at least 30 days with an antipsychotic in a therapeutic dose according to local guidelines other than clozapine and olanzapine before the screening phase is needed. For non-treatment-naïve patients (defined as having been treated for more than 30 days with an antipsychotic), a discontinuation of a foregoing antipsychotic treatment prior to the screening phase within a maximum of six months (=180 days) is possible (corresponding to the estimated average time for an antipsychotic washout phase and the expected time to develop a relapse of the disease). For patients being treated with a long-acting antipsychotic (other than PP3M), an inclusion is possible if inclusion date corresponds to the planned date of the next injection plus five to seven days. For patients being treated with oral olanzapine, an inclusion is possible if this treatment has lasted for no longer than 2 weeks prior to inclusion and if exclusion criteria 8 is not fulfilled.
6.Clinical need for a medication switch because of clinical inefficacy or side-effects or clinical need for a reintroduction of an antipsychotic treatment after treatment discontinuation prior to the screening phase (see 5.)
7.Moderate symptomatology on the PANSS, defined as a score = 4 for two or more symptoms from P1-P7 or a score of = 6 for one symptom from P1-P7 (minimum threshold definition) at screening
8.Male participants and female participants who are not capable of bearing children or who use a method of contraception that is medically approved by the health authority of the respective country at screening
This includes:
a.A woman who is not capable of bearing a child is defined as follows: post-menopausal (12 months natural (spontaneous) amenorrhea or 6 months spontaneous amenorrhea with serum-FSH-values (follicle-stimulating hormone) of >40 mIU/mL); 6 weeks after a bilateral ovariectomy with or without hysterectomy or sterilization by means of tubal ligation
b.A woman capable of bearing child is defined as follows: a woman who is physiologically capable of becoming pregnant, including women whose occupation, lifestyle or sexual orientation exclude sexual intercourse with a male partner and women whose partners have been sterilized by vasectomy or other measures
c.Medically-approved methods of contraception can include the following: hormonal contraceptives, intrauterine device and double barrier method. Acceptable preventive measures can include total abstinence at the discretion of the investigator, in cases where compliance is ensured because of the study participant’s age, occupation, lifestyle or sexual orientation. Periodical abstinence (e.g. calendar, ovulation, symptothermal methods or abstinence until the 4th day after the ovulation) as well as coitus interruptus are not acceptable methods of contraception
d.A reliable method of contraception (CTFG guideline) must be used for the entire duration of the study

Are the trial subjects under 18? no
Number of subjects for th

Exclusion Criteria

1.Patients who are not suitable for the study in the opinion of the investigator (including acutely suicidal patients)
2.Patients who are unable to give informed consent
3.Coercive treatment at the time of study inclusion
4.White blood cell count (WBC) at inclusion not meeting the requirements for clozapine use in Germany according to the SmPC. Patients must have normal leukocyte findings (white blood cell count = 3500/mm3 (= 3.5x109/l), and Absolute Neutrophil Count (ANC) = 2000/mm3 (= 2.0x109/l) at the screening visit
5.The presence of one or more of the contraindications against any of the study drugs as mentioned in the SmPC
6.Treatment-naïve or treatment-resistant schizophrenia. Treatment-naïve will be defined as no previous antipsychotic treatment or a maximum of 30 days of treatment. Treatment resistance is defined as two antipsychotic trials (with antipsychotics from two different chemical classes) for a period of = 6 weeks with CPZ equivalent doses = 600 mg/day (Howes, McCutcheon et al. 2017), both of which took place immediately before the screening phase
7.Diagnosis of primary substance dependency other than nicotine: exclusion alcohol dependency via AUDIT-screening (Bohn, Babor et al. 1995, Babor 2001) and DSM V criteria (MINI-interview); exclusion of other drug dependencies other than alcohol and nicotine: drug screening of urine and DSM V criteria (MINI-interview: patient fulfilling early (> 3 months) or sustained (>12 months) remission criteria and/or with low severity of substance use disorder according to MINI (DSM-V) are eligible for the study)
8.Documented previous non-response to an 8-week drug trial with olanzapine or any documented previous treatment with clozapine
9.Documented intolerance to one of the study drugs
10.Pregnancy (incl. positive blood pregnancy test) / lactation (female patients)

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective is to investigate the symptomatic remission rates in non-treatment-refractory patients with schizophrenia randomized to either early clozapine or olanzapine over an 8-week period. ;Secondary Objective: Secondary objectives include differences in side effects, symptom severity, safety measures and cognitive functions as detailed below.;Primary end point(s): Relative frequency of patients in the clozapine group in remission (Remission in Schizophrenia Working Group [RSWG] consensus criteria) at week 8 compared to the olanzapine group.;Timepoint(s) of evaluation of this end point: Screening, Baseline vist 5, visit 9

Secondary Outcome Measures

Name	Time	Method

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