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

NCT07283965 | Not Yet Recruiting FDA Drug

• 1 other identifier: Pharmaco111525
• Study Type: observational
• Target: 15,000
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background. Zanubrutinib 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 zanubrutinib 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 zanubrutinib or acalabrutinib. Patients will be divided into 2 groups based on zanubrutinib or acalabrutinib exposure. After propensity score matching (PSM), Cox proportional hazard models will be used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) to compare the 2 matched groups. The appropriateness of the proportional hazard assumption will be examined and risk differences (RDs) will be used if appropriate. Results will summarized with the use of Kaplan-Meier survival curves.

Conditions

BTK Inhibitors; Cardiovascular Diseases; Chronic B-cell Malignancies

Outcome Measures

Primary Outcomes (1)

• Risk of incident atrial fibrillation in patients exposed to zanubrutinib compared with those exposed to acalabrutinib in the matched cohort.

  from the introduction of the BTK inhibitor and up to 5 years

Secondary Outcomes (6)

• Risk of all-cause mortality in patients exposed to zanubrutinib compared with those exposed to acalabrutinib in thematched cohort

  from the introduction of the BTK inhibitor and up to 5 years

• Risk of incident intra-cerebral hemorrhage in patients exposed to zanubrutinib compared with those exposed to acalabrutinib in the matched cohort

  from the introduction of the BTK inhibitor and up to 5 years

• Risk of incident major bleeding in patients exposed to zanubrutinib compared with those exposed to acalabrutinib in the matched cohort

  from the introduction of the BTK inhibitor and up to 5 years

• Risk of incident hypertension in patients exposed to zanubrutinib compared with those exposed to acalabrutinib in the matched cohort

  from the introduction of the BTK inhibitor and up to 5 years

• Risk of incident MACE (composite) in patients exposed to zanubrutinib compared with those exposed to acalabrutinib in the matched cohort

  from the introduction of the BTK inhibitor and up to 5 years

Study Arms (2)

Zanubrutinib

Adult patients with a chronic B-cell malignancy exposed to zanubrutinib

Drug: Zanubrutinib

Acalabrutinib

Adult patients with a chronic B-cell malignancy exposed to acalabrutinib

Drug: Acalabrutinib

Interventions

Acalabrutinib DRUG

Adult patients with a chronic B-cell malignancy exposed to acalabrutinib

Acalabrutinib

Zanubrutinib DRUG

Adult patients with a chronic B-cell malignancy exposed to zanubrutinib

Zanubrutinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

adult patients - diagnose with chronic B-cell malignancies expose to zanubrutinib or acalabrutinib in the TrinetX database

You may qualify if:

• adult patients
• diagnose with chronic B-cell malignancies
• exposed to zanubrutinib or acalabrutinib

You may not qualify if:

• none

Sponsors & Collaborators

• University Hospital, Caen: lead

MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

zanubrutinib; acalabrutinib

Central Study Contacts

Joachim Alexandre, MD, PhD

CONTACT

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

Study Design

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

Study Record Dates

• First Submitted: November 26, 2025
• First Posted: December 16, 2025
• Study Start: December 22, 2025
• Primary Completion: January 15, 2026
• Study Completion: March 31, 2026
• Last Updated: December 16, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share