Comparison of Antipsychotic Combination Treatment of Olanzapine and Amisulpride to Monotherapy

NCT01609153 | Completed Phase 4 DMC

• 1 other identifier: COMBINE
• Study Type: interventional
• Target: 328
• Locations: 1 country
• Sites: 21

Brief Summary

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

Conditions

Schizophrenia; Schizoaffective Disorder

Keywords

schizophrenia; amisulpride; olanzapine; polypharmacy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• 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.

• 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.

• PANSS total score reduction from baseline to week 2 as a predictor of the change after 8 weeks

  8 weeks

• Serious adverse drug reactions

  16 weeks

• Change of clinical condition measured by Clinical Global Impression Scale (CGI scale)

  every 2 weeks from baseline up to week 16

Study Arms (3)

Olanzapine or Placebo

ACTIVE COMPARATOR

Drug: Amisulpride; Drug: Olanzapine and Amisulpride

Amisulpride or Placebo

ACTIVE COMPARATOR

Drug: Olanzapine; Drug: Olanzapine and Amisulpride

Olanzapine and Amisulpride

ACTIVE COMPARATOR

Drug: Olanzapine; Drug: Amisulpride

Interventions

Olanzapine DRUG

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

Also known as: Zyprexa

Amisulpride or Placebo; Olanzapine and Amisulpride

Amisulpride DRUG

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

Also known as: Amisulprid Hexal

Olanzapine and Amisulpride; Olanzapine or Placebo

Olanzapine and Amisulpride DRUG

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

Also known as: Zyprexa, Amisuprid Hexal

Amisulpride or Placebo; Olanzapine or Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Heinrich-Heine University, Duesseldorf: lead

Study Sites (21)

RWTH Aachen

Aachen, 52074, Germany

Location

Rheinhessen Fachklinik Alzey

Alzey, 55232, Germany

Location

Rhein-Mosel-Fachklinik Andernach

Andernach, 56626, Germany

Location

Bezirkskliniken Schwaben, Bezirkskrankenhaus Augsburg

Augsburg, 89156, Germany

Location

Charite-Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

LVR-Klinikum Köln

Cologne, 51109, Germany

Location

LWL-Klinik Dortmund

Dortmund, 44281, Germany

Location

LVR-Klinikum Düsseldorf

Düsseldorf, 40629, Germany

Location

Universitätsmedizin Göttingen

Göttingen, 37075, Germany

Location

Zentrum für Seelische Gesundheit Kreiskliniken Darmstadt-Dieburg Standort: Groß-Umstadt

Groß-Umstadt, 64823, Germany

Location

Klinik für Psychiatrie, Psychotherapie und Psychosomatik am Bezirkskrankehaus Günzburg

Günzburg, 89312, Germany

Location

Klinik für Psychiatrie, Sozialpsychiatrie und Psychotherapie Medizinische Hochschule Hannover (MHH)

Hanover, 30625, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, 69115, Germany

Location

LVR-Klinik Langenfeld

Langenfeld, 40764, Germany

Location

Universitätsklinikum Leipzig, Klinik und Poliklinik für Psychiatrie und Psychotherapie

Leipzig, 04103, Germany

Location

Universitätsmedizin Mainz Klinik für Psychiatrie und Psychotherapie

Mainz, 55131, Germany

Location

Zentralinstitut für Seelische Gesundheit

Mannheim, 68159, Germany

Location

LMU München

München, 80336, Germany

Location

TU München

München, 81675, Germany

Location

Bezirksklinikum Regensburg, Klinik für Psychiatrie und Psychotherapie

Regensburg, 93053, Germany

Location

Universitätsklinikum Würzburg

Würzburg, 97080, Germany

Location

Related Publications (1)

• 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.

  PMID: 35276079 DERIVED

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Olanzapine; Amisulpride

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Christian Schmidt-Kraepelin, Dr.

  Heinrich-Heine University, Duesseldorf

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2012
• First Posted: May 31, 2012
• Study Start: June 1, 2012
• Primary Completion: April 1, 2019
• Study Completion: April 1, 2019
• Last Updated: April 16, 2019

Record last verified: 2019-04

Locations

DE (21)