Trial document




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  DRKS00000304

Trial Description

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Title

Clinical effectiveness of the newer antipsychotic compounds olanzapine, quetiapine and aripiprazole in comparison with low dose conventional antipsychotics (haloperidol and flupentixol) in patients with schizophrenia

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Trial Acronym

NeSSy (Neuroleptic Strategy Study)

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URL of the Trial

[---]*

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Brief Summary in Lay Language

To treat schizophrenic disorders psychiatrists may use different types of medication. For a long time now drugs known as "typical" (conventional) antipsychotics have been available on the market. In recent years however developments referred to as "atypical" antipsychotics have become an alternative. The prevailing opinion in the psychiatric field is that these newer antipsychotic drugs are superior regarding effectiveness and tolerance.
Their general superiority to the conventional drugs could not be clearly shown yet. Some clinical trials did not even find a relevant difference between specific typical and atypical drugs. Conclusive clinical trials are missing which meet the variety of the disease pattern, give sufficient choices of treatment possibilities, cover assessment of patient related outcomes and include a wide range of patients.
This randomized, controlled and double blind project should answer open questions. It's innovative qualities are the comparison of different therapeutic strategies ("typical vs. atypical"), an improved biometrical design, a clinically relevant objective and criteria to include or exclude patients close to clinical reality. To take into account the individual characteristics of a patient the attending psychiatrist can make a limited choice of treatment. Another innovation is to determine the serum concentration of the study drug twice in order to gain more reliable information about the actual amount of agent in the patient's blood.
This approach might also serve as model for other clinical trials with similar subjects.

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Brief Summary in Scientific Language

There is agreement in the psychiatry community that the so-called atypical antipsychotics should be considered first choice in the treatment of schizophrenic disorders (DGPPN 2005). However, the general superiority of these newer antipsychotic drugs over the older conventional drugs could not be clearly demonstrated in recent controlled clinical trials. The discrepancy between every day´s clinical perception and the results of clinical trials raises the question whether the studies performed so far employed the adequate methodological approach to represent the daily practice situation which is characterized by a wide variety of duration and type of the schizophrenic disorder, concomitant diseases, and medications. Moreover, some studies might not have been focused adequately on patient-relevant outcome variables.
The present study project is designed to answer these open questions. The innovative character of the study design is
1) that different neuroleptic strategies will be compared rather than single antipsychotic drugs, using
2) an enhanced biometric design, that provides a choice of treatment with respect to the individual patient though the trial as such is randomised controlled and double blind;
3) that clinically relevant endpoints such as quality of life will be the primary variables, and
4) inclusion and exclusion criteria lead to a study population representing clinical every day practice as near as possible.
Another innovatory procedure is that serum levels of the study drugs will be recorded twice during the study. The authors hope that their design might yield transfer effects for other clinical trials facing similar problems.

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Organizational Data

  •   DRKS00000304
  •   2009/12/21
  •   [---]*
  •   yes
  •   Approved
  •   EK HB 2009-10-041 FF, Ethikkommission des Landes Bremen
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Secondary IDs

  •   U1111-1112-9727 
  •   2009-010966-47 
  •   4035749 
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Health Condition or Problem studied

  •   F20 -  Schizophrenia
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Interventions/Observational Groups

  •   Oral administration of two tablets of the following (atypical) drugs during the first two weeks: Aripiprazole 5 mg in the morning or either Olanzapine 5 mg, Quetiapine 200 mg in the evening. Supplemented with placebo in the morning or evening, double-blind. After the first 14 days the medication dosage can be increased up to 4 tablets per day. During the whole treatment period the patient may be given up to 7.5 mg of Lorazepam or 8 mg of Biperiden.
  •   Oral administration of two tablets of the following (typical) drugs during the first two weeks: Flupentixol 3 mg or Haloperidol 1.5 mg in the evening. Supplemented with placebo in the morning, double-blind. After the first 14 days the medication dosage can be increased up to 4 tablets per day. During the whole treatment period the patient may be given up to 7.5 mg of Lorazepam or 8 mg of Biperiden.
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Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Blinded
  •   patient/subject, investigator/therapist
  •   Placebo
  •   Treatment
  •   Parallel
  •   IV
  •   [---]*
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Primary Outcome

Two primary efficacy endpoints used in the study. 1) Quality of life from the patient's perspective with SF-36 (interviewer version with a time frame of one week) and 2) the change in clinical status from the perspective of the investigator with CGI. The change from baseline at week 24 is measured by AUC based on logarithmic transformed time scale.

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Secondary Outcome

Secondary endpoints:
Subscores of SF-36, SWN-K, PSP, PANSS, CGI-Matrix (treatment response).

Assessment of safety:
Adverse events, drop-out rates, SAS / AIMS / BARS and sexual dysfunction changes. Metabolic side effects: body mass index (BMI), waist circumference, HbA1c, fast blood glucose levels, lipid profile changes (total cholesterol / LDL cholesterol /HDL cholesterol, triglycerides) from baseline to week 24 (visit 6), serum concentration of the respective study drug (olanzapine, quetiapine, aripiprazole, haloperidol, flupentixol).

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

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

  •   Actual
  •   2010/04/08
  •   181
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   65   Years
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Additional Inclusion Criteria

Patients with schizophrenia, age 18-65, necessity to establish new or change antipsychotic treatment due to unsatisfying results or side effects.

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Exclusion Criteria

Acute suicidal tendency, "Einwilligungsvorbehalt (BGB)" or "Unterbringung (PsychKG)", organic psychosis, history of malignant neuroleptic syndrome, QTc interval greater than or equal to 0.5 s / history of congenital QTc prolongation.

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Addresses

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    • Universität Bremen Kompetenzzentrum für Klinische Studien Bremen, Biometrie
    • Mr.  Prof. Dr. Dr. h.c.   Jürgen  Timm 
    • Linzer Str. 4
    • 28359  Bremen
    • Germany
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    • Universität Bremen, Kooperationszentrum Medizin Kompetenzzentrum für Klinische Studien Bremen
    • Mr.  Prof. Dr. med.  Eckart  Rüther 
    • Linzer Str. 4
    • 28359  Bremen
    • Germany
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    • Klinik für Psychiatrie, Psychotherapie und Psychosomatik, Universitätsklinikum Aachen
    • Mr.  Prof. Dr.  Gerhard   Gründer 
    • Pauwelsstraße 30
    • 52074  Aachen
    • Germany
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Sources of Monetary or Material Support

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    • Bundesministerium für Bildung und Forschung
    • Heinemannstr. 2
    • 53175  Bonn
    • Germany
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    •   0228/9957-0
    •   0228/9957-83601
    •   [---]*
    •   http://www.bmbf.de
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Status

  •   Recruiting complete, follow-up complete
  •   2014/03/31
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* This entry means the parameter is not applicable or has not been set.