Clinical trial NCT00856583: Safety Study of Sertindole Versus Risperidone Under Normal Conditions of Use
Official title: Sertindole Versus Risperidone Safety Outcome Study: a Randomised, Partially-blinded, Parallel-group, Active-controlled, Post-marketing Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Lead sponsor: H. Lundbeck A/S
Sponsor class: INDUSTRY
First posted: 2009-03-06
Enrollment: 9809
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Number of Participants With All-cause Mortality
timeFrame: 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
measure: Second Primary Outcome: Number of Participants With Cardiac Events, Including Arrhythmias, Requiring Hospitalisation
timeFrame: 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 outcomes:
measure: Cause-specific Mortality: Number of Participants With Cardiac Deaths - ISC
timeFrame: 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
measure: Cause-specific Mortality: Number of Participants With Completed Suicides - ISC
timeFrame: 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
measure: Cause-specific Mortality: Number of Participants With Other Than Cardiac Deaths and Completed Suicides - ISC
timeFrame: 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
measure: Cause-specific Mortality: Number of Participants With Cardiac Deaths - MedDRA
timeFrame: 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
measure: Cause-specific Mortality: Number of Participants With Completed Suicides - MedDRA
timeFrame: 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
measure: Cause-specific Mortality: Number of Participants With Other Than Cardiac Deaths and Completed Suicides - MedDRA
timeFrame: 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
measure: Number of Participants With Suicide Attempts (Fatal and Non-fatal) - ISC
timeFrame: 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
measure: Number of Participants With Suicide Attempts (Fatal and Non-fatal) - MedDRA
timeFrame: 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
measure: Number of Participants With Hospitalisations, Excluding Hospitalisations Related to the Primary Psychiatric Disease
timeFrame: 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
measure: Number of Participants With Discontinuation of Treatment for Any Reason Other Than Study Closure
timeFrame: 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
Other outcomes:
Locations:
Study officials:
affiliation: LundbeckClinicalTrials@lundbeck.com
name: Email contact via H. Lundbeck A/S
role: STUDY_DIRECTOR
References:
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.
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.
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.
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.
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.