Clinical trial NCT01609153: Comparison of Antipsychotic Combination Treatment of Olanzapine and Amisulpride to Monotherapy
Official title: A Randomized Double-blind Controlled Trial to Assess the Benefits of Olanzapine and Amisulpride Combination Treatment in Acutely Ill Schizophrenia Patients. - COMBINE
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Schizophrenia
Schizoaffective Disorder
Keywords: schizophrenia
amisulpride
olanzapine
polypharmacy
Lead sponsor: Heinrich-Heine University, Duesseldorf
Sponsor class: OTHER
First posted: 2012-05-31
Enrollment: 328
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A study to examine whether an antipsychotic combination treatment of olanzapine and amisulpride is more effective than olanzapine and amisulpride alone.

Detailed description: Polypharmacy in antipsychotic therapy is an important issue when treating patients with schizophrenia. It is not well confirmed that a combination of two antipsychotic drugs lead to therapeutic benefit in contrast to monotherapy. However there is a highly frequent practice of combining atypical non-clozapine treatment that could be due to potential benefits when seeking alternatives to a high rate of non-response in acute phase. Therefore there is a need for further trials of sufficient power to address efficacy and safety issues of this regimen. Combining two selected atypical drugs in a complementary way may minimize side-effects and enhance efficacy. In order to specify these advantages it is intend to examine approaches to combination treatment: Amisulpride and olanzapine show complementing receptor binding profiles and have shown to have efficacy and good tolerability when administered in combination in retrospective studies. The object of this trial is to study whether acutely ill patients with combination of amisulpride and olanzapine are more frequently in symptomatic remission after 8 weeks than those with olanzapine or amisulpride monotherapy.

Eligibility criteria: Inclusion Criteria:

* Patients with schizophrenia and schizoaffective disorder according to International Classification of Diseases (ICD-10);
* age 18-65;
* Positive and Negative Symptom Scale Total-Score ≥ 70 and two items of the positive symptom subscale ≥4.
* voluntary treatment after written informed consent
* legal capacity
* exclusion of pregnancy by laboratory test (Beta HCG)

Exclusion Criteria:

* participation in other interventional studies with drugs or medical devices
* first episode patients
* physical disease that might have effects on the conduct or evaluation of the trial
* contraindications to medication according to experts information
* oversensitivity to active substance or other component of the drugs used
* known clozapine resistance
* suicidal ideation
* pregnancy or lactation
* which of pregnancy or absence save contraception
* dependency to sponsor or investigator
* institutionalization through judicial or regulatory order
* oversensitivity to placebo (mannite/aerosil)

Primary outcomes:
measure: Symptomatic improvement of schizophrenia after 8 weeks of treatment in comparison to time of inclusion of patient measured py Positive and Negative Symptom Scale (PANSS)
timeFrame: 8 weeks
Secondary outcomes:
measure: Symptomatic improvement of schizophrenia after 16 weeks of treatment in comparison to time of inclusion of patient measured py PANSS total score reduction
timeFrame: 16 weeks.
measure: Symptomatic improvement of schizophrenia from baseline to week 2 up to week 16 measured by PANSS total score reduction.
timeFrame: Every 2 weeks up to week 16.
measure: PANSS total score reduction from baseline to week 2 as a predictor of the change after 8 weeks
timeFrame: 8 weeks
measure: Serious adverse drug reactions
timeFrame: 16 weeks
measure: Change of clinical condition measured by Clinical Global Impression Scale (CGI scale)
timeFrame: every 2 weeks from baseline up to week 16
measure: Change of the subjective well-being measured by Subjective Wellbeing under Neuroleptics Scale (SWN-K)
timeFrame: between week 0, 8, 16
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: RWTH Aachen
city: Alzey
country: Germany
facility: Rheinhessen Fachklinik Alzey
city: Andernach
country: Germany
facility: Rhein-Mosel-Fachklinik Andernach
city: Augsburg
country: Germany
facility: Bezirkskliniken Schwaben, Bezirkskrankenhaus Augsburg
city: Berlin
country: Germany
facility: Charite-Universitätsmedizin Berlin
city: Dortmund
country: Germany
facility: LWL-Klinik Dortmund
city: Düsseldorf
country: Germany
facility: LVR-Klinikum Düsseldorf
city: Groß-Umstadt
country: Germany
facility: Zentrum für Seelische Gesundheit Kreiskliniken Darmstadt-Dieburg Standort: Groß-Umstadt
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen
city: Günzburg
country: Germany
facility: Klinik für Psychiatrie, Psychotherapie und Psychosomatik am Bezirkskrankehaus Günzburg
city: Hannover
country: Germany
facility: Klinik für Psychiatrie, Sozialpsychiatrie und Psychotherapie Medizinische Hochschule Hannover (MHH)
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Köln
country: Germany
facility: LVR-Klinikum Köln
city: Langenfeld
country: Germany
facility: LVR-Klinik Langenfeld
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig, Klinik und Poliklinik für Psychiatrie und Psychotherapie
city: Mainz
country: Germany
facility: Universitätsmedizin Mainz Klinik für Psychiatrie und Psychotherapie
city: Mannheim
country: Germany
facility: Zentralinstitut für Seelische Gesundheit
city: München
country: Germany
facility: LMU München
city: München
country: Germany
facility: TU München
city: Regensburg
country: Germany
facility: Bezirksklinikum Regensburg, Klinik für Psychiatrie und Psychotherapie
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg
Study officials:
affiliation: Heinrich-Heine University, Duesseldorf
name: Christian Schmidt-Kraepelin, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schmidt-Kraepelin C, Feyerabend S, Engelke C, Riesbeck M, Meisenzahl-Lechner E, Verde PE, Correll CU, Kluge M, Makiol C, Neff A, Lange C, Englisch S, Zink M, Langguth B, Poeppl TB, Reske D, Gouzoulis-Mayfrank E, Grunder G, Hasan A, Brockhaus-Dumke A, Jager M, Baumgartner J, Leucht S, Cordes J; COMBINE Study Group. Amisulpride and olanzapine combination treatment versus each monotherapy in acutely ill patients with schizophrenia in Germany (COMBINE): a double-blind randomised controlled trial. Lancet Psychiatry. 2022 Apr;9(4):291-306. doi: 10.1016/S2215-0366(22)00032-3. Epub 2022 Mar 8.