Clozapine and Haematologic Malignancies: Observational and Retrospective Study Using the WHO Pharmacovigilance Database

• Conditions: Leukemia; Lymphoma
• Interventions: Drug: Clozapine

• Registration Number: NCT04074213
• Lead Sponsor: University Hospital, Caen

Brief Summary

Clozapine may lead to various adverse reactions, including neutropenia and agranulocytosis. This study investigates reports of lymphoma and leukaemias for clozapine in the World Health Organization's (WHO) global database of individual safety case reports (VigiBase).

Detailed Description

Clozapine is responsible of a wide range of adverse side effects.The investigators use VigiBase, the World Health Organization (WHO) database of individual safety case reports, to identify cases of haematologic malignancies following treatment with clozapine.

Study Timeline

• Study Start: 2019-03-01
• Status Verified: 2019-08
• Study First Submitted: 2019-08-19
• Study First Submitted QC: 2019-08-27
• Last Update Submitted: 2019-08-27
• Study First Posted: 2019-08-30
• Last Update Posted: 2019-08-30
• Primary Completion: 2024-03-01
• Study Completion: 2024-08-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 1000000

Inclusion Criteria

• Case reported in the World Health Organization (WHO) database of individual safety case reports to 03/05/2019
• Adverse events reported were including the MedDRA terms: Malignant Lymphoma (SMQ), Leukaemia (HLGT)
• Patients treated with at least one liable antipsychotic drug (ATC class N05A)

Exclusion Criteria

• Chronology not compatible between the drug and the toxicity

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Haematologic malignancies with clozapine	Clozapine	Cases reported in the World Health Organization (WHO) database of patients treated by Clozapine, with a chronology compatible with the drug toxicity

Primary Outcome Measures

Name	Time	Method
Correlation between clozapine and haematologic malignancies using a disproportionality analysis in Individual Case Reports involving at least one liable antipsychotic drug in Vigibase®.	Case reported in the World Health Organization (WHO) of individual safety case reports to March 2019 ]	Study the correlation between clozapine and haematologic malignancies by comparing the proportion of Individual Case Reports (ICSRs) of hematologic malignancies with liable clozapine with the proportion of ICSRs of hematologic malignancies with at least one liable antipsychotic.

Secondary Outcome Measures

Name	Time	Method
investigate a potential dose-dependent effect	Case reported in the World Health Organization (WHO) of individual safety case reports to March 2019 ]	To investigate a potential dose-dependent effect, we will collect the clozapine daily dose from all clozapine ICSRs. In ICSRs with liable clozapine, the clozapine daily dose in mg will be divided into quartiles. A disproportionality analysis will be performed to evaluate the effect of the clozapine daily dose on the reporting of lymphomas and leukaemia. A significant difference of proportion of reports of haematologic malignancies between each quartile will be researched.
Description of the clinical features of clozapine-related haematologic malignancies	Case reported in the World Health Organization (WHO) of individual safety case reports to March 2019 ]	Description of the clinical features (mean age, sex ratio, time to onset, daily dose) of clozapine-related haematologic malignancies according to the main clinical subtypes

Trial Locations

Locations (1)

Caen University Hospital, Department of Pharmacology; 🇫🇷 Caen, Normandie, France