Safety Study of Sertindole Versus Risperidone Under Normal Conditions of Use (SCoP)
Primary Purpose
Schizophrenia
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Sertindole
Risperidone
Sponsored by
About this trial
This is an interventional prevention trial for Schizophrenia
Eligibility Criteria
Inclusion Criteria:
- The patient has signed the Informed Consent Form or, if he/she is not able to sign it (according to the ICH GCP guidelines and the Declaration of Helsinki), the patient's legal representative has signed the Informed Consent Form
- The patient has been diagnosed with schizophrenia
- Based on the patient's clinical status, new or change of antipsychotic treatment is indicated
- The patient is at least 18 years of age
- The patient meets the criteria set out in the national SPCs for sertindole and risperidone. For those countries in which sertindole was not marketed, the EU SPC applied
Exclusion Criteria:
- The last treatment taken by the patient was sertindole or risperidone
- The patient has never previously received any antipsychotic drug therapy
- The patient has contraindications to treatment with either sertindole or risperidone
- In addition to sertindole/risperidone, treatment with another antipsychotic is indicated
- The patient is homeless
- The patient has previously been included in one of the two H. Lundbeck A/S post-marketing studies, 99823 or 99824
- The patient is, in the opinion of the investigator, unlikely to comply with the study protocol or unsuitable for any other reason
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Sertindole
Risperidone
Arm Description
Normally in the range of 4 to 20 mg/day
Normally in the range of 2 to 8 mg/day
Outcomes
Primary Outcome Measures
Number of Participants With All-cause Mortality
The analysis was based on all deaths from the Whole Randomised Treatment (WRT)+30 days period and the Only Randomised Treatment (ORT) period, respectively
Second Primary Outcome: Number of Participants With Cardiac Events, Including Arrhythmias, Requiring Hospitalisation
Second primary endpoint: a serious adverse event where the patient was hospitalised and for which the Independent Safety Committee (ISC) classified the event as a cardiac event with documented arrhythmia. The analysis of this outcome was not performed due to low number of events. The presented analysis is a replacement analysis using all cardiac events, including arrhythmias, that required hospitalisation
Secondary Outcome Measures
Cause-specific Mortality: Number of Participants With Cardiac Deaths - ISC
The analysis was based on all deaths from the WRT+30 days period using the classification performed by the ISC.
The ISC reviewed and classified those adverse events which resulted in death or hospitalisation or were possible suicide attempts and this review was blinded to exposure. The definition of cardiac death was intentionally wide; sudden or unexplained deaths were assumed to be cardiac if there was no non-cardiac explanation. To ensure consistent evaluation and classification, the ISC decided a priori to classify all instances of self harm as possible suicide.
Cause-specific Mortality: Number of Participants With Completed Suicides - ISC
The analysis was based on all deaths from the WRT+30 days period using the classification performed by the ISC.
The ISC reviewed and classified those adverse events which resulted in death or hospitalisation or were possible suicide attempts and this review was blinded to exposure. The definition of cardiac death was intentionally wide; sudden or unexplained deaths were assumed to be cardiac if there was no non-cardiac explanation. To ensure consistent evaluation and classification, the ISC decided a priori to classify all instances of self harm as possible suicide.
Cause-specific Mortality: Number of Participants With Other Than Cardiac Deaths and Completed Suicides - ISC
The analysis was based on all deaths from the WRT+30 days period using the classification performed by the ISC.
The ISC reviewed and classified those adverse events which resulted in death or hospitalisation or were possible suicide attempts and this review was blinded to exposure. The definition of cardiac death was intentionally wide; sudden or unexplained deaths were assumed to be cardiac if there was no non-cardiac explanation. To ensure consistent evaluation and classification, the ISC decided a priori to classify all instances of self harm as possible suicide.
Cause-specific Mortality: Number of Participants With Cardiac Deaths - MedDRA
The analysis was based on all deaths from the WRT+30 days period using the classification based upon the Medical Dictionary for Regulatory Activities (MedDRA) terminology, that is, as reported by the investigator
Cause-specific Mortality: Number of Participants With Completed Suicides - MedDRA
The analysis was based on all deaths from the WRT+30 days period using the classification based upon MedDRA terminology, that is, as reported by the investigator
Cause-specific Mortality: Number of Participants With Other Than Cardiac Deaths and Completed Suicides - MedDRA
The analysis was based on all deaths from the WRT+30 days period using the classification based upon MedDRA terminology, that is, as reported by the investigator
Number of Participants With Suicide Attempts (Fatal and Non-fatal) - ISC
The analysis was based on all suicides and suicide attempts from the WRT+30 days period using the classification performed by the ISC.
The ISC reviewed and classified those adverse events which resulted in death or hospitalisation or were possible suicide attempts and this review was blinded to exposure. The definition of cardiac death was intentionally wide; sudden or unexplained deaths were assumed to be cardiac if there was no non-cardiac explanation. To ensure consistent evaluation and classification, the ISC decided a priori to classify all instances of self harm as possible suicide.
Number of Participants With Suicide Attempts (Fatal and Non-fatal) - MedDRA
The analysis was based on all suicides and suicide attempts from the WRT+30 days period using the classification based upon MedDRA terminology, that is, as reported by the investigator
Number of Participants With Hospitalisations, Excluding Hospitalisations Related to the Primary Psychiatric Disease
The analysis was based on time from start of study drug to first hospitalisation during the WRT+30 days period
Number of Participants With Discontinuation of Treatment for Any Reason Other Than Study Closure
The analysis was based on time from start of study drug until stop of study drug for any reason other than sponsor closure of the study
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00856583
Brief Title
Safety Study of Sertindole Versus Risperidone Under Normal Conditions of Use
Acronym
SCoP
Official Title
Sertindole Versus Risperidone Safety Outcome Study: a Randomised, Partially-blinded, Parallel-group, Active-controlled, Post-marketing Study
Study Type
Interventional
2. Study Status
Record Verification Date
August 2011
Overall Recruitment Status
Completed
Study Start Date
July 2002 (undefined)
Primary Completion Date
February 2008 (Actual)
Study Completion Date
February 2008 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
H. Lundbeck A/S
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of the study is to determine whether there is an increased all-cause mortality in sertindole-treated patients in comparison to patients treated with a well-known antipsychotic (risperidone) when used under normal marketed conditions in the treatment of schizophrenia.
Detailed Description
The Committee for Medicinal Products for Human Use (CHMP) requested a post-marketing study to ascertain that the favourable benefit-risk profile and low mortality rates seen in the clinical studies with sertindole would not be offset by higher mortality rates when sertindole was used under more normal conditions of use. It was recognised that, in a clinical trial setting, strict patient selection and monitoring could lead to higher compliance in patient management and thereby to a lower mortality rate. Study 99824 was therefore designed in collaboration with the CHMP as an open-label, randomised study with minimum study management that focused on mortality and general patient safety. The duration of the treatment period was not fixed. No efficacy measures were included.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
9809 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sertindole
Arm Type
Experimental
Arm Description
Normally in the range of 4 to 20 mg/day
Arm Title
Risperidone
Arm Type
Active Comparator
Arm Description
Normally in the range of 2 to 8 mg/day
Intervention Type
Drug
Intervention Name(s)
Sertindole
Other Intervention Name(s)
Serdolect
Intervention Description
Sertindole was supplied as 4, 12, 16, and 20 mg tablets. The start and maintenance dosages as well as dose titration were set by the investigator, in accordance with the national Summary of Product Characteristics (SPC) for sertindole; in countries where sertindole was not marketed, the European Union (EU) SPC applied (all national and EU SPCs were essentially identical). Recommended dose range: 12 to 20 mg/day. The investigators were instructed to contact H. Lundbeck A/S if they deemed it necessary to increase the dose of sertindole to 24 mg/day, which was allowed in exceptional cases
Intervention Type
Drug
Intervention Name(s)
Risperidone
Other Intervention Name(s)
Risperdal
Intervention Description
Risperidone was supplied as 1, 2, 3, and 4 mg tablets. The start and maintenance dosages as well as dose titration were set by the investigator, in accordance with the national SPC for risperidone. Recommended dose range: 2 to 8 mg/day
Primary Outcome Measure Information:
Title
Number of Participants With All-cause Mortality
Description
The analysis was based on all deaths from the Whole Randomised Treatment (WRT)+30 days period and the Only Randomised Treatment (ORT) period, respectively
Time Frame
As study design allowed patients to continue study drug until the study was closed, many patients were followed for several years, with an overall median time period of approximately 14 months
Title
Second Primary Outcome: Number of Participants With Cardiac Events, Including Arrhythmias, Requiring Hospitalisation
Description
Second primary endpoint: a serious adverse event where the patient was hospitalised and for which the Independent Safety Committee (ISC) classified the event as a cardiac event with documented arrhythmia. The analysis of this outcome was not performed due to low number of events. The presented analysis is a replacement analysis using all cardiac events, including arrhythmias, that required hospitalisation
Time Frame
As study design allowed patients to continue study drug until the study was closed, many patients were followed for several years, with an overall median time period of approximately 14 months
Secondary Outcome Measure Information:
Title
Cause-specific Mortality: Number of Participants With Cardiac Deaths - ISC
Description
The analysis was based on all deaths from the WRT+30 days period using the classification performed by the ISC.
The ISC reviewed and classified those adverse events which resulted in death or hospitalisation or were possible suicide attempts and this review was blinded to exposure. The definition of cardiac death was intentionally wide; sudden or unexplained deaths were assumed to be cardiac if there was no non-cardiac explanation. To ensure consistent evaluation and classification, the ISC decided a priori to classify all instances of self harm as possible suicide.
Time Frame
As study design allowed patients to continue study drug until the study was closed, many patients were followed for several years, with an overall median time period of approximately 14 months
Title
Cause-specific Mortality: Number of Participants With Completed Suicides - ISC
Description
The analysis was based on all deaths from the WRT+30 days period using the classification performed by the ISC.
The ISC reviewed and classified those adverse events which resulted in death or hospitalisation or were possible suicide attempts and this review was blinded to exposure. The definition of cardiac death was intentionally wide; sudden or unexplained deaths were assumed to be cardiac if there was no non-cardiac explanation. To ensure consistent evaluation and classification, the ISC decided a priori to classify all instances of self harm as possible suicide.
Time Frame
As study design allowed patients to continue study drug until the study was closed, many patients were followed for several years, with an overall median time period of approximately 14 months
Title
Cause-specific Mortality: Number of Participants With Other Than Cardiac Deaths and Completed Suicides - ISC
Description
The analysis was based on all deaths from the WRT+30 days period using the classification performed by the ISC.
The ISC reviewed and classified those adverse events which resulted in death or hospitalisation or were possible suicide attempts and this review was blinded to exposure. The definition of cardiac death was intentionally wide; sudden or unexplained deaths were assumed to be cardiac if there was no non-cardiac explanation. To ensure consistent evaluation and classification, the ISC decided a priori to classify all instances of self harm as possible suicide.
Time Frame
As study design allowed patients to continue study drug until the study was closed, many patients were followed for several years, with an overall median time period of approximately 14 months
Title
Cause-specific Mortality: Number of Participants With Cardiac Deaths - MedDRA
Description
The analysis was based on all deaths from the WRT+30 days period using the classification based upon the Medical Dictionary for Regulatory Activities (MedDRA) terminology, that is, as reported by the investigator
Time Frame
As study design allowed patients to continue study drug until the study was closed, many patients were followed for several years, with an overall median time period of approximately 14 months
Title
Cause-specific Mortality: Number of Participants With Completed Suicides - MedDRA
Description
The analysis was based on all deaths from the WRT+30 days period using the classification based upon MedDRA terminology, that is, as reported by the investigator
Time Frame
As study design allowed patients to continue study drug until the study was closed, many patients were followed for several years, with an overall median time period of approximately 14 months
Title
Cause-specific Mortality: Number of Participants With Other Than Cardiac Deaths and Completed Suicides - MedDRA
Description
The analysis was based on all deaths from the WRT+30 days period using the classification based upon MedDRA terminology, that is, as reported by the investigator
Time Frame
As study design allowed patients to continue study drug until the study was closed, many patients were followed for several years, with an overall median time period of approximately 14 months
Title
Number of Participants With Suicide Attempts (Fatal and Non-fatal) - ISC
Description
The analysis was based on all suicides and suicide attempts from the WRT+30 days period using the classification performed by the ISC.
The ISC reviewed and classified those adverse events which resulted in death or hospitalisation or were possible suicide attempts and this review was blinded to exposure. The definition of cardiac death was intentionally wide; sudden or unexplained deaths were assumed to be cardiac if there was no non-cardiac explanation. To ensure consistent evaluation and classification, the ISC decided a priori to classify all instances of self harm as possible suicide.
Time Frame
As study design allowed patients to continue study drug until the study was closed, many patients were followed for several years, with an overall median time period of approximately 14 months
Title
Number of Participants With Suicide Attempts (Fatal and Non-fatal) - MedDRA
Description
The analysis was based on all suicides and suicide attempts from the WRT+30 days period using the classification based upon MedDRA terminology, that is, as reported by the investigator
Time Frame
As study design allowed patients to continue study drug until the study was closed, many patients were followed for several years, with an overall median time period of approximately 14 months
Title
Number of Participants With Hospitalisations, Excluding Hospitalisations Related to the Primary Psychiatric Disease
Description
The analysis was based on time from start of study drug to first hospitalisation during the WRT+30 days period
Time Frame
As study design allowed patients to continue study drug until the study was closed, many patients were followed for several years, with an overall median time period of approximately 14 months
Title
Number of Participants With Discontinuation of Treatment for Any Reason Other Than Study Closure
Description
The analysis was based on time from start of study drug until stop of study drug for any reason other than sponsor closure of the study
Time Frame
As study design allowed patients to continue study drug until the study was closed, many patients were followed for several years, with an overall median time period of approximately 14 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
The patient has signed the Informed Consent Form or, if he/she is not able to sign it (according to the ICH GCP guidelines and the Declaration of Helsinki), the patient's legal representative has signed the Informed Consent Form
The patient has been diagnosed with schizophrenia
Based on the patient's clinical status, new or change of antipsychotic treatment is indicated
The patient is at least 18 years of age
The patient meets the criteria set out in the national SPCs for sertindole and risperidone. For those countries in which sertindole was not marketed, the EU SPC applied
Exclusion Criteria:
The last treatment taken by the patient was sertindole or risperidone
The patient has never previously received any antipsychotic drug therapy
The patient has contraindications to treatment with either sertindole or risperidone
In addition to sertindole/risperidone, treatment with another antipsychotic is indicated
The patient is homeless
The patient has previously been included in one of the two H. Lundbeck A/S post-marketing studies, 99823 or 99824
The patient is, in the opinion of the investigator, unlikely to comply with the study protocol or unsuitable for any other reason
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Email contact via H. Lundbeck A/S
Organizational Affiliation
LundbeckClinicalTrials@lundbeck.com
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
18384186
Citation
Peuskens J, Tanghoj P, Mittoux A; Sertindole Cohort. The Sertindole Cohort Prospective (SCoP) study: rationale, design and methodology. Pharmacoepidemiol Drug Saf. 2008 May;17(5):425-33. doi: 10.1002/pds.1594.
Results Reference
result
PubMed Identifier
20384598
Citation
Thomas SH, Drici MD, Hall GC, Crocq MA, Everitt B, Lader MH, Le Jeunne C, Naber D, Priori S, Sturkenboom M, Thibaut F, Peuskens J, Mittoux A, Tanghoj P, Toumi M, Moore ND, Mann RD. Safety of sertindole versus risperidone in schizophrenia: principal results of the sertindole cohort prospective study (SCoP). Acta Psychiatr Scand. 2010 Nov;122(5):345-55. doi: 10.1111/j.1600-0447.2010.01563.x.
Results Reference
result
PubMed Identifier
20926264
Citation
Crocq MA, Naber D, Lader MH, Thibaut F, Drici M, Everitt B, Hall GC, Le Jeunne C, Mittoux A, Peuskens J, Priori S, Sturkenboom M, Thomas SH, Tanghoj P, Toumi M, Mann R, Moore ND. Suicide attempts in a prospective cohort of patients with schizophrenia treated with sertindole or risperidone. Eur Neuropsychopharmacol. 2010 Dec;20(12):829-38. doi: 10.1016/j.euroneuro.2010.09.001.
Results Reference
result
PubMed Identifier
20820795
Citation
De Hert M, Mittoux A, He Y, Peuskens J. Metabolic parameters in the short- and long-term treatment of schizophrenia with sertindole or risperidone. Eur Arch Psychiatry Clin Neurosci. 2011 Jun;261(4):231-9. doi: 10.1007/s00406-010-0142-x. Epub 2010 Sep 5.
Results Reference
result
PubMed Identifier
20732794
Citation
De Hert M, Mittoux A, He Y, Peuskens J. A head-to-head comparison of sertindole and risperidone on metabolic parameters. Schizophr Res. 2010 Nov;123(2-3):276-7. doi: 10.1016/j.schres.2010.07.030. Epub 2010 Aug 21. No abstract available.
Results Reference
result
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Safety Study of Sertindole Versus Risperidone Under Normal Conditions of Use
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