SchizophreniaPhase 4COMBINENCT01609153
Comparison of Antipsychotic Combination Treatment of Olanzapine and Amisulpride to Monotherapy
A Phase 4 study testing Olanzapine, Amisulpride and Olanzapine and Amisulpride in people with Schizophrenia and Schizoaffective Disorder, run by Heinrich-Heine University, Duesseldorf at 21 sites in Germany.
Trial summary
A study to examine whether an antipsychotic combination treatment of olanzapine and amisulpride is more effective than olanzapine and amisulpride alone. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia, Schizoaffective Disorder
- What is being tested?
- Olanzapine, Amisulpride and Olanzapine and Amisulpride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 328 participants
- Where
- 21 sitesGermany
- Study dates
- Jun 2012to Apr 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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)
Trial locations and contacts
21 sites in 1 country.
21 sites in 1 country
Germany21 sites
RWTH Aachen
Aachen, 52074
Rheinhessen Fachklinik Alzey
Alzey, 55232
Rhein-Mosel-Fachklinik Andernach
Andernach, 56626
Bezirkskliniken Schwaben, Bezirkskrankenhaus Augsburg
Augsburg, 89156
Charite-Universitätsmedizin Berlin
Berlin, 10117
LVR-Klinikum Köln
Cologne, 51109
LWL-Klinik Dortmund
Dortmund, 44281
LVR-Klinikum Düsseldorf
Düsseldorf, 40629
Universitätsmedizin Göttingen
Göttingen, 37075
Zentrum für Seelische Gesundheit Kreiskliniken Darmstadt-Dieburg Standort: Groß-Umstadt
Groß-Umstadt, 64823
Klinik für Psychiatrie, Psychotherapie und Psychosomatik am Bezirkskrankehaus Günzburg
Günzburg, 89312
Klinik für Psychiatrie, Sozialpsychiatrie und Psychotherapie Medizinische Hochschule Hannover (MHH)
Hanover, 30625
Universitätsklinikum Heidelberg
Heidelberg, 69115
LVR-Klinik Langenfeld
Langenfeld, 40764
Universitätsklinikum Leipzig, Klinik und Poliklinik für Psychiatrie und Psychotherapie
Leipzig, 04103
Universitätsmedizin Mainz Klinik für Psychiatrie und Psychotherapie
Mainz, 55131
Zentralinstitut für Seelische Gesundheit
Mannheim, 68159
LMU München
München, 80336
TU München
München, 81675
Bezirksklinikum Regensburg, Klinik für Psychiatrie und Psychotherapie
Regensburg, 93053
Universitätsklinikum Würzburg
Würzburg, 97080
About this study
Official title: A Randomized Double-blind Controlled Trial to Assess the Benefits of Olanzapine and Amisulpride Combination Treatment in Acutely Ill Schizophrenia Patients. - COMBINE
A study to examine whether an antipsychotic combination treatment of olanzapine and amisulpride is more effective than olanzapine and amisulpride alone.
Read the 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.
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Being tested
- Olanzapine, Amisulpride, Olanzapine and Amisulpride
- Keywords
- schizophrenia, amisulpride, olanzapine, polypharmacy
- Medical subject headings
- Schizophrenia, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OlanzapineDrug
Also called Zyprexa
Coated tablet 5-20 mg milligram(s) per day for 16 weeks
AmisulprideDrug
Also called Amisulprid Hexal
200-800 mg milligram(s)per day for 16 weeks
Olanzapine and AmisulprideDrug
Also called Zyprexa, Amisuprid Hexal
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
| Study group | Role | What they receive |
|---|---|---|
| Olanzapine or Placebo | Active comparator | Not described Receives: Drug: Amisulpride; Drug: Olanzapine and Amisulpride |
| Amisulpride or Placebo | Active comparator | Not described Receives: Drug: Olanzapine; Drug: Olanzapine and Amisulpride |
| Olanzapine and Amisulpride | Active comparator | Not described Receives: Drug: Olanzapine; Drug: Amisulpride |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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
To study whether a combination treatment of olanzapine and amisulpride show a PANSS total score reduction from baseline to week 16.
Measured: 16 weeks.
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.
Measured: 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
Whether a change of PANSS total score reduction from baseline to week 2 is a predictor of the change after 8 weeks
Measured: 8 weeks
Serious adverse drug reactions
Frequency and severity of serious adverse drug reactions
Measured: 16 weeks
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)
Measured: every 2 weeks from baseline up to week 16
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)
Measured: between week 0, 8, 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2012 (estimated)
- Study startJun 2012
- Primary completionApr 2019
- Study completionApr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Heinrich-Heine University, DuesseldorfThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 328 participants (actual)
Sponsor and investigators
- Lead sponsor
- Heinrich-Heine University, Duesseldorf
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Christian Schmidt-Kraepelin, Dr., Principal investigator, Heinrich-Heine University, Duesseldorf
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01609153
- Sponsor's protocol ID
- COMBINE
- Acronym
- COMBINE
- Status last verified
- Apr 2019
- First submitted
- 23 May 2012
- Last updated
- 16 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 35276079
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Double-blind Controlled Trial to Assess the Benefits of Olanzapine and Amisulpride Combination Treatment in Acutely Ill Schizophrenia Patients. - COMBINE
- ClinicalTrials.gov ID
- NCT01609153
- Acronym / sponsor ID
- COMBINE / COMBINE
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Keywords
- schizophrenia, amisulpride, olanzapine, polypharmacy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 328 participants (actual)
- Lead sponsor
- Heinrich-Heine University, DuesseldorfUniversity, hospital or other
- Study start
- Jun 2012 (actual)
- Primary completion
- Apr 2019 (actual)
- Study completion
- Apr 2019 (actual)
- First posted
- 31 May 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OlanzapineAlso: ZyprexaCoated tablet 5-20 mg milligram(s) per day for 16 weeks | Drug | Amisulpride or Placebo, Olanzapine and Amisulpride |
| AmisulprideAlso: Amisulprid Hexal200-800 mg milligram(s)per day for 16 weeks | Drug | Olanzapine and Amisulpride, Olanzapine or Placebo |
| Olanzapine and AmisulprideAlso: Zyprexa, Amisuprid HexalZyprexa: 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 | Drug | Amisulpride or Placebo, Olanzapine or Placebo |
Primary outcome
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)
Time frame: 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)
6 secondary outcomes
Symptomatic improvement of schizophrenia after 16 weeks of treatment in comparison to time of inclusion of patient measured py PANSS total score reduction
Time frame: 16 weeks.
Symptomatic improvement of schizophrenia from baseline to week 2 up to week 16 measured by PANSS total score reduction.
Time frame: 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
Time frame: 8 weeks
Serious adverse drug reactions
Time frame: 16 weeks
Change of clinical condition measured by Clinical Global Impression Scale (CGI scale)
Time frame: every 2 weeks from baseline up to week 16
Change of the subjective well-being measured by Subjective Wellbeing under Neuroleptics Scale (SWN-K)
Time frame: between week 0, 8, 16
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2019.
- Derived from this study: PubMed 35276079Schmidt-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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christian Schmidt-Kraepelin, Dr. principal investigator
Heinrich-Heine University, Duesseldorf
21 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Olanzapine, Amisulpride and Olanzapine and Amisulpride in people with Schizophrenia and Schizoaffective Disorder, run by Heinrich-Heine University, Duesseldorf at 21 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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) (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01609153, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2019.