NCT06224452

Is Ibrutinib-related Atrial Fibrillation Dose Dependent

Is Ibrutinib-related Atrial Fibrillation Dose Dependent: Insights From the WHO Pharmacovigilance Database

• Status: Unknown
• Phase: —
• Study type: Observational
• Enrollment: 18,000 (estimated)
• Sponsor: University Hospital, Caen · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: —

Summary

Ibrutinib, an oral inhibitor of Bruton tyrosine kinase (BTK), has recently revolutionized the treatment of various chronic B-cell malignancies and particularly chronic lymphocytic leukemia (CLL). Atrial fibrillation (AF) has early emerged as a cardiovascular adverse effect (CVAE) of ibrutinib but underlying mechanisms of IRAF are not fully understood. While a dose-reduction or an interruption of ibrutinib is mentioned in the summary of product characteristics of ibrutinib, any beneficial effect on IRAF management of such a management is unclear. The main aim of this study is to determine if IRAF is a dose-dependent CVAE in chronic B-cell malignancies patients by studying the association between ibrutinib dose and IRAF reporting in Vigibase®, the World Health Organization (WHO) pharmacovigilance database.

Detailed description

Ibrutinib, an oral inhibitor of Bruton tyrosine kinase (BTK), has recently revolutionized the treatment of various chronic B-cell malignancies and particularly chronic lymphocytic leukemia (CLL). Atrial fibrillation (AF) has early emerged as a cardiovascular adverse effect (CVAE) of ibrutinib. In phase 3 randomized clinical trials (RCT), ibrutinib exhibits a ≈4-fold increase-risk of AF compared with controls (pooled relative-risk (RR) 3.9; 95% confidence interval (CI): (2.0-7.5); p\<0.0001). The annualized incidence rate of ibrutinib-related AF (IRAF) reporting in clinical trials is estimated to 4.9 (95% CI: 2.9-8.3) per 100 person-years. IRAF risk persists throughout ibrutinib exposition and seems to be cumulative with the extension of follow-up and cardiac monitoring. Underlying mechanisms of IRAF are not fully understood. Ibrutinib potently inhibits multiple off-target kinases at therapeutic concentrations. While a dose-reduction or an interruption of ibrutinib is mentioned in the summary of product characteristics of ibrutinib, any beneficial effect on IRAF management of such a management is unclear. The main aim of this study is to determine if IRAF is a dose-dependent CVAE in chronic B-cell malignancies patients by studying the association between ibrutinib dose and IRAF reporting in Vigibase®, the World Health Organization (WHO) pharmacovigilance database.

Conditions

• Hematological Malignancy
• Atrial Fibrillation

Interventions

Type	Name	Description
DRUG	ibrutinib exposure	We will extract all atrial fibrillation cases involving adult patients associated with ibrutinib exposure with an available ibrutinib daily dose

Timeline

• Start date: 2024-03-01
• Primary completion: 2024-05-01
• Completion: 2024-07-01
• First posted: 2024-01-25
• Last updated: 2024-03-05

Locations

1 site across 1 country: France

Regulatory

• FDA-regulated drug study