COMBINE: Comparison of Antipsychotic Combination Treatment of Olanzapine and Amisulpride to Monotherapy

Sponsor

Heinrich-Heine University, Duesseldorf (Other)

Overall Status

Completed

CT.gov ID

NCT01609153

Collaborator

(none)

328

Enrollment

Locations

Arms

Actual Duration (Months)

15.6

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia Schizoaffective Disorder	Drug: Olanzapine Drug: Amisulpride Drug: Olanzapine and Amisulpride	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

328 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 1, 2012

Actual Primary Completion Date :

Apr 1, 2019

Actual Study Completion Date :

Apr 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Olanzapine or Placebo	Drug: Amisulpride 200-800 mg milligram(s)per day for 16 weeks Other Names: Amisulprid Hexal Drug: 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 Other Names: Zyprexa, Amisuprid Hexal
Active Comparator: Amisulpride or Placebo	Drug: Olanzapine Coated tablet 5-20 mg milligram(s) per day for 16 weeks Other Names: Zyprexa Drug: 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 Other Names: Zyprexa, Amisuprid Hexal
Active Comparator: Olanzapine and Amisulpride	Drug: Olanzapine Coated tablet 5-20 mg milligram(s) per day for 16 weeks Other Names: Zyprexa Drug: Amisulpride 200-800 mg milligram(s)per day for 16 weeks Other Names: Amisulprid Hexal

Arm

Intervention/Treatment

Active Comparator: Olanzapine or Placebo

Drug: Amisulpride

200-800 mg milligram(s)per day for 16 weeks

Other Names:

Amisulprid Hexal

Drug: 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

Other Names:

Zyprexa, Amisuprid Hexal

Active Comparator: Amisulpride or Placebo

Drug: Olanzapine

Coated tablet 5-20 mg milligram(s) per day for 16 weeks

Other Names:

Zyprexa

Drug: 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

Other Names:

Zyprexa, Amisuprid Hexal

Active Comparator: Olanzapine and Amisulpride

Drug: Olanzapine

Coated tablet 5-20 mg milligram(s) per day for 16 weeks

Other Names:

Zyprexa

Drug: Amisulpride

200-800 mg milligram(s)per day for 16 weeks

Other Names:

Amisulprid Hexal

Outcome Measures

Primary Outcome Measures

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]
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)

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	RWTH Aachen	Aachen	Germany	52074
2	Rheinhessen Fachklinik Alzey	Alzey	Germany	55232
3	Rhein-Mosel-Fachklinik Andernach	Andernach	Germany	56626
4	Bezirkskliniken Schwaben, Bezirkskrankenhaus Augsburg	Augsburg	Germany	89156
5	Charite-Universitätsmedizin Berlin	Berlin	Germany	10117
6	LWL-Klinik Dortmund	Dortmund	Germany	44281
7	LVR-Klinikum Düsseldorf	Düsseldorf	Germany	40629
8	Zentrum für Seelische Gesundheit Kreiskliniken Darmstadt-Dieburg Standort: Groß-Umstadt	Groß-Umstadt	Germany	64823
9	Universitätsmedizin Göttingen	Göttingen	Germany	37075
10	Klinik für Psychiatrie, Psychotherapie und Psychosomatik am Bezirkskrankehaus Günzburg	Günzburg	Germany	89312
11	Klinik für Psychiatrie, Sozialpsychiatrie und Psychotherapie Medizinische Hochschule Hannover (MHH)	Hannover	Germany	30625
12	Universitätsklinikum Heidelberg	Heidelberg	Germany	69115
13	LVR-Klinikum Köln	Köln	Germany	51109
14	LVR-Klinik Langenfeld	Langenfeld	Germany	40764
15	Universitätsklinikum Leipzig, Klinik und Poliklinik für Psychiatrie und Psychotherapie	Leipzig	Germany	04103
16	Universitätsmedizin Mainz Klinik für Psychiatrie und Psychotherapie	Mainz	Germany	55131
17	Zentralinstitut für Seelische Gesundheit	Mannheim	Germany	68159
18	LMU München	München	Germany	80336
19	TU München	München	Germany	81675
20	Bezirksklinikum Regensburg, Klinik für Psychiatrie und Psychotherapie	Regensburg	Germany	93053
21	Universitätsklinikum Würzburg	Würzburg	Germany	97080