Comparison of Antipsychotic Combination Treatment of Olanzapine and Amisulpride to Monotherapy

Schizophrenia Clinical Trial

— COMBINE  

Official title:

A Randomized Double-blind Controlled Trial to Assess the Benefits of Olanzapine and Amisulpride Combination Treatment in Acutely Ill Schizophrenia Patients. - COMBINE

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01609153
• Other study ID #: COMBINE
• Status: Completed
• Phase: Phase 4
• Start date: June 2012
• Est. completion date: April 2019

Study information

• Verified date: April 2019
• Source: Heinrich-Heine University, Duesseldorf
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 328
• Est. completion date: April 2019
• Est. primary completion date: April 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Psychotic Disorders
• Schizoaffective Disorder
• Schizophrenia

Intervention

Drug:
• Olanzapine
Coated tablet 5-20 mg milligram(s) per day for 16 weeks
• Amisulpride
200-800 mg milligram(s)per day for 16 weeks
• Olanzapine and Amisulpride
Zyprexa: Coated tablet 5-20 mg milligram(s) per day for 16 weeks Amisulpride: Coated tablet 200-800 mg milligram(s)per day for 16 weeks

Locations

Country	Name	City	State
Germany	RWTH Aachen	Aachen
Germany	Rheinhessen Fachklinik Alzey	Alzey
Germany	Rhein-Mosel-Fachklinik Andernach	Andernach
Germany	Bezirkskliniken Schwaben, Bezirkskrankenhaus Augsburg	Augsburg
Germany	Charite-Universitätsmedizin Berlin	Berlin
Germany	LWL-Klinik Dortmund	Dortmund
Germany	LVR-Klinikum Düsseldorf	Düsseldorf
Germany	Universitätsmedizin Göttingen	Göttingen
Germany	Zentrum für Seelische Gesundheit Kreiskliniken Darmstadt-Dieburg Standort: Groß-Umstadt	Groß-Umstadt
Germany	Klinik für Psychiatrie, Psychotherapie und Psychosomatik am Bezirkskrankehaus Günzburg	Günzburg
Germany	Klinik für Psychiatrie, Sozialpsychiatrie und Psychotherapie Medizinische Hochschule Hannover (MHH)	Hannover
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	LVR-Klinikum Köln	Köln
Germany	LVR-Klinik Langenfeld	Langenfeld
Germany	Universitätsklinikum Leipzig, Klinik und Poliklinik für Psychiatrie und Psychotherapie	Leipzig
Germany	Universitätsmedizin Mainz Klinik für Psychiatrie und Psychotherapie	Mainz
Germany	Zentralinstitut für Seelische Gesundheit	Mannheim
Germany	LMU München	München
Germany	TU München	München
Germany	Bezirksklinikum Regensburg, Klinik für Psychiatrie und Psychotherapie	Regensburg
Germany	Universitätsklinikum Würzburg	Würzburg

Sponsors (1)

Lead Sponsor	Collaborator
Heinrich-Heine University, Duesseldorf

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Whether there is a 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)	8 weeks
Secondary	Symptomatic improvement of schizophrenia after 16 weeks of treatment in comparison to time of inclusion of patient measured py PANSS total score reduction	To study whether a combination treatment of olanzapine and amisulpride show a PANSS total score reduction from baseline to week 16.	16 weeks.
Secondary	Symptomatic improvement of schizophrenia from baseline to week 2 up to week 16 measured by PANSS total score reduction.	Whether a combination treatment of olanzapine and amisulpride show a PANSS total score reduction from baseline to every 2 weeks up to week 16.	Every 2 weeks up to week 16.
Secondary	PANSS total score reduction from baseline to week 2 as a predictor of the change after 8 weeks	Whether a change of PANSS total score reduction from baseline to week 2 is a predictor of the change after 8 weeks	8 weeks
Secondary	Serious adverse drug reactions	Frequency and severity of serious adverse drug reactions	16 weeks
Secondary	Change of clinical condition measured by Clinical Global Impression Scale (CGI scale)	Whether there is a change of clinical condition measured by Clinical Global Impression Scale (CGI scale)	every 2 weeks from baseline up to week 16
Secondary	Change of the subjective well-being measured by Subjective Wellbeing under Neuroleptics Scale (SWN-K)	Whether there is a change of the subjective well-being measured by Subjective Wellbeing under Neuroleptics Scale(SWN-K)	between week 0, 8, 16