Ibrutinib and Acalabrutinib Use and Risk of Atrial Fibrillation in Patients With Chronic B-cell Malignancies

Active, not recruiting

• Conditions: Chronic B-cell Malignancies; BTK Inhibitors; Cardiovascular Diseases
• Interventions: Drug: BTK inhibitor (Ibrutinib or Acalabrutinib)

• Registration Number: NCT06561243
• Lead Sponsor: University Hospital, Caen

Brief Summary

Background. Ibrutinib and acalabrutinib are both associated with an increased risk of atrial fibrillation (AF) but AF comparative risk between these 2 BTK inhibitors (BTKis) remains largely unknown.

Objectives. Our aim was to examine the risk of developing incident AF with ibrutinib exposure compared with acalabrutinib exposure.

Methods. Using the TriNetX research network database, authors will conduct a retrospective cohort analysis of deidentified, aggregate adult patients with chronic B-cell malignancies and exposed to ibrutinib or acalabrutinib. Patients will be divided into 2 groups based on ibrutinib or acalabrutinib exposure. After propensity score matching (PSM), hazard ratios (HRs) and their associated 95% confidence intervals (CIs) will be used to compare AF risk during follow-up between the matched 2 groups.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-07-24
• Study Start: 2024-07-25
• Status Verified: 2024-08
• Study First Submitted QC: 2024-08-17
• Last Update Submitted: 2024-08-19
• Study First Posted: 2024-08-20
• Last Update Posted: 2024-08-21
• Primary Completion: 2024-09-30
• Study Completion: 2024-10-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 15000

Inclusion Criteria

• adult patients
• diagnose with chronic B-cell malignancies using ICD-10-CM codes C91 (lymphoid leukemia), C88.0 (Waldenström macroglobulinemia), C83.1 (mantle cell lymphoma), C81-C96 (malignant neoplasms of lymphoid, hematopoietic and related tissue) or C95 (leukemia of unspecified cell type)
• expose to ibrutinib or acalabrutinib determined by the Anatomical Therapeutic Chemical codes

Exclusion Criteria

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Ibrutinib	BTK inhibitor (Ibrutinib or Acalabrutinib)	Adult patients with a chronic B-cell malignancy exposed to ibrutinib
Acalabrutinib	BTK inhibitor (Ibrutinib or Acalabrutinib)	Adult patients with a chronic B-cell malignancy exposed to acalabrutinib

Primary Outcome Measures

Name	Time	Method
Risk of incident atrial fibrillation in patients exposed to ibrutinib compared with those exposed to acalabrutinib in the whole matched cohort.	from the introduction of the BTK inhibitor and up to 120 months	ICD-10-CM code I48 will be used to identify AF during follow-up

Secondary Outcome Measures

Name	Time	Method
Risk of all-cause mortality in patients exposed to ibrutinib compared with those exposed to acalabrutinib in the whole matched cohort	from the introduction of the BTK inhibitor and up to 120 months	death from any cause during follow-up
Risk of incident intra-cerebral hemorrhage in patients exposed to ibrutinib compared with those exposed to acalabrutinib in the whole matched cohort	from the introduction of the BTK inhibitor and up to 120 months	ICD-10-CM code ill be used to identify intra-cerebral hemorrhage during follow-up
Risk of incident major bleeding in patients exposed to ibrutinib compared with those exposed to acalabrutinib in the whole matched cohort	from the introduction of the BTK inhibitor and up to 120 months	ICD-10-CM code ill be used to identify major bleeding during follow-up
Risk of incident atrial fibrillation in patients exposed to ibrutinib compared with those exposed to acalabrutinib in a matched cohort categorized according their baseline cardiovascular risk level for developing AF	from the introduction of the BTK inhibitor and up to 120 months	ICD-10-CM code ill be used to identify AF during follow-up
Risk of incident MACE (composite) in patients exposed to ibrutinib compared with those exposed to acalabrutinib in the whole matched cohort	from the introduction of the BTK inhibitor and up to 120 months	ICD-10-CM code ill be used to identify MACE (composite of acute myocardial infraction, ischemic stroke or thromboembolism and heart failure) during follow-up
Risk of incident ventricular tachycardia/ventricular fibrillation/cardiac arrest (composite) in patients exposed to ibrutinib compared with those exposed to acalabrutinib in the whole matched cohort	from the introduction of the BTK inhibitor and up to 120 months	ICD-10-CM code ill be used to identify VT/VF/cardiac arrest (composite of ventricular tachycardia, ventricular fibrillation and cardiac arrest) during follow-up
Risk of incident atrial fibrillation in patients exposed to ibrutinib compared with those exposed to acalabrutinib in a matched cohort restricted to patients aged ≤75 and to patients aged >75	from the introduction of the BTK inhibitor and up to 120 months	ICD-10-CM code I48 will be used to identify AF during follow-up
Risk of incident hypertension in patients exposed to ibrutinib compared with those exposed to acalabrutinib in the whole matched cohort	from the introduction of the BTK inhibitor and up to 120 months	ICD-10-CM code ill be used to identify hypertension during follow-up

Trial Locations

Locations (1)

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