Is Ibrutinib-related Atrial Fibrillation Dose Dependent

NCT06224452 | Unknown FDA Drug

• 1 other identifier: Pharmaco011624
• Study Type: observational
• Target: 18,000
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hematological Malignancy; Atrial Fibrillation

Outcome Measures

Primary Outcomes (1)

• to determine the influence of ibrutinib dosing on IRAF reporting. Results were expressed as 2-by2 comparisons against the lowest dosing regimen (140mg/day).

  Disproportionality estimates will be perform using both univariate and multivariate analyses and a global p-value will measure the difference between dosing regimen

  Cases reported in the World Health Organization (WHO) of individual safety case reports to 26th July 2023

Secondary Outcomes (5)

• Description of ibrutinib-related atrial fibrillation cases

  Cases reported in the World Health Organization (WHO) of individual safety case reports to 26th July 2023

• To determine the influence of ibrutinib dosing on IRAF reporting after exclusion of IRAF cases containing concurrent anticoagulant and/or antiarrhythmic drugs, assuming this approach could exclude reports with history of AF preceding IRAF reporting

  Cases reported in the World Health Organization (WHO) of individual safety case reports to 26th July 2023

• To determine the influence of ibrutinib dosing on IRAF reporting according to the underlying chronic B-cell malignancy indication.

  Cases reported in the World Health Organization (WHO) of individual safety case reports to 26th July 2023

• To determine if the time to IRAF onset is dependent of the ibrutinib dosing regimen

  Cases reported in the World Health Organization (WHO) of individual safety case reports to 26th July 2023

• Sensitivity analysis will also be performed regarding the influence of ibrutinib dosing on 2 dose-dependent ADRs (neutropenia and thrombocytopenia) reporting related to ibrutinib exposure

  Cases reported in the World Health Organization (WHO) of individual safety case reports to 26th July 2023

Interventions

ibrutinib exposure DRUG

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

* ibrutinib-related atrial fibrillation reports in Vigibase at the time of data extraction * involving adult patients * with an available ibrutinib daily dose

You may qualify if:

• ibrutinib-related atrial fibrillation reports in Vigibase at the time of data extraction
• involving adult patients
• with an available ibrutinib daily dose

You may not qualify if:

• minors
• no ibrutinib dose available

Sponsors & Collaborators

• University Hospital, Caen: lead

Study Sites (1)

Caen University Hospital, Department of Pharmacology

Caen, Normandy, France

Location

Related Publications (1)

• Alexandre J, Font J, Angelique DS, Delapierre B, Damaj G, Plane AF, Legallois D, Milliez P, Dolladille C, Chretien B. Is ibrutinib-related atrial fibrillation dose dependent? Insights from an individual case level analysis of the World Health Organization pharmacovigilance database. Leukemia. 2024 Dec;38(12):2628-2635. doi: 10.1038/s41375-024-02413-5. Epub 2024 Sep 19.

  PMID: 39300222 DERIVED

MeSH Terms

Conditions

Hematologic Neoplasms; Atrial Fibrillation

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Joachim Alexandre, MD

  University Hospital, Caen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joachim Alexandre, MD

CONTACT

+33231064670; alexandre-j@chu-caen.fr

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2024
• First Posted: January 25, 2024
• Study Start: March 1, 2024
• Primary Completion: May 1, 2024
• Study Completion: July 1, 2024
• Last Updated: March 5, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)