Clinical trial NCT06095791: Identification of Immunomodulators Associated With Atrial Fibrillation Reporting: Analysis of the WHO Pharmacovigilance Database
Official title: Identification of Immunomodulators Associated With Atrial Fibrillation Reporting: Analysis of the WHO Pharmacovigilance Database
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Atrial Fibrillation
Keywords: Immunomodulators
Pharmacovigilance
Atrial fibrillation
Lead sponsor: University Hospital, Caen
Sponsor class: OTHER
First posted: 2023-10-23
Enrollment: 4000000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Every patients in the World Health Organization (WHO) database of individual safety case reports to 01/09/2022 included with at least one immunomodulator.

Brief summary: Atrial fibrillation is the most prevalent sustained arrhythmia worldwide with a great morbimortality. Some populations are more at risk to develop atrial fibrillation like patients suffering from inflammatory diseases or patients suffering from cancers. This is at least explained by the inflammatory environment related to these both conditions. Many experimental studies and clinical studies support the role of inflammation and immunity in atrial fibrillation genesis by modulating atrial action potential et by promoting fibrosis.

Immunomodulators are drugs used to stimulate or inhibit the immune system for two main indications : cancers and immune disorder diseases which both promote atrial fibrillation. Due to their interactions with inflammation and immunity, immunomodulatores may further promote the risk of atrial fibrillation, particularly in a population already at risk.

Based on the World Health Organization global database, the main objective of this study is to investigate the association between immunomodulators and the occurrence of atrial fibrillation reported in the database.

A disproportionality analysis will be performed. It will aim to assess whether immunomodulators are associated with a greater risk of atrial fibrillation.

Secondary objectives aim to describe the cases of atrial fibrillation among immunomodulators associated with atrial fibrillation in the main analysis, to describe coprescription among immunomodulators associated with atrial fibrillation in the main analysis, to analyse the role of immunomoduloators medical indication in the overrisk of atrial fibrillation, and to try to highlight some immune mechanisms promoting atrial fibrillation regarding the immunomodulators associated with atrial fibrillation in the main analysis.


Eligibility criteria: Inclusion Criteria:

* Case reported in the World Health Organization (WHO) database of individual safety case reports to 01/09/2022
* Patients treated with FDA approved immunomodulators (approval the 1st January 2023).

Primary outcomes:
measure: Association between atrial fibrillation and immunomodulators
timeFrame: Case reported in the World Health Organization (WHO) of individual safety case reports to September 2022
Secondary outcomes:
measure: Descriptive analysis of the atrial fibrillation cases with immunomodulators significantly associated with atrial fibrillation in the primary analysis
timeFrame: Case reported in the World Health Organization (WHO) of individual safety case reports to September 2022
measure: Identification of molecular/cellular pathway through mechanism of action of immunomodulators associated with AF in the primary analysis.
timeFrame: Case reported in the World Health Organization (WHO) of individual safety case reports to September 2022
measure: Exploratory analysis: association between immunomodulators medical indication and atrial fibrillation.
timeFrame: Case reported in the World Health Organization (WHO) of individual safety case reports to September 2022
measure: Descriptive analysis of the coprescription between immunomodulators associated with atrial fibrillation in the main analysis.
timeFrame: Case reported in the World Health Organization (WHO) of individual safety case reports to September 2022
Other outcomes:
Locations:
city: Caen
country: France
facility: Alexandre Joachim
state: Basse Normandie
Study officials:
References:
citation: Alexandre J, Salem JE, Moslehi J, Sassier M, Ropert C, Cautela J, Thuny F, Ederhy S, Cohen A, Damaj G, Vilque JP, Plane AF, Legallois D, Champ-Rigot L, Milliez P, Funck-Brentano C, Dolladille C. Identification of anticancer drugs associated with atrial fibrillation: analysis of the WHO pharmacovigilance database. Eur Heart J Cardiovasc Pharmacother. 2021 Jul 23;7(4):312-320. doi: 10.1093/ehjcvp/pvaa037.
citation: Lazzerini PE, Capecchi PL, Laghi-Pasini F. Systemic inflammation and arrhythmic risk: lessons from rheumatoid arthritis. Eur Heart J. 2017 Jun 7;38(22):1717-1727. doi: 10.1093/eurheartj/ehw208.
citation: Guo Y, Lip GY, Apostolakis S. Inflammation in atrial fibrillation. J Am Coll Cardiol. 2012 Dec 4;60(22):2263-70. doi: 10.1016/j.jacc.2012.04.063.
citation: Lazzerini PE, Laghi-Pasini F, Acampa M, Srivastava U, Bertolozzi I, Giabbani B, Finizola F, Vanni F, Dokollari A, Natale M, Cevenini G, Selvi E, Migliacci N, Maccherini M, Boutjdir M, Capecchi PL. Systemic Inflammation Rapidly Induces Reversible Atrial Electrical Remodeling: The Role of Interleukin-6-Mediated Changes in Connexin Expression. J Am Heart Assoc. 2019 Aug 20;8(16):e011006. doi: 10.1161/JAHA.118.011006. Epub 2019 Aug 19.