Cardiovascular Complications of Ibrutinib Therapy

NCT05939752 | Terminated

• 1 other identifier: ROBERT AOI 2022
• Study Type: observational
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

Ibrutinib, the first BTK inhibitor (BTKI) to be approved, improves progression-free survival (PFS) and overall survival (OS) over alternative therapies in relapsed/refractory and treatment-naive chronic lymphocytic leukemia (CLL). Ibrutinib has also been found to be effective in mantle cell lymphoma, Waldenström's macroglobulinemia and marginal zone lymphoma. However, ibrutinib treatment is associated with an increased risk of atrial fibrillation (AF), with an estimated 2-year AF rate of 16% in patients treated with ibrutinib during a median follow-up of 28 months. In most studies, AF was identified by reports as a treatment-related adverse event, and systematic screening for AF was not performed. As AF is often paroxysmal, the more intensive the screening, the higher the incidence. In a prospective cohort study of 53 patients treated with ibrutinib for CLL, patients were monitored by pulse palpation and ECG every 3 months. The cumulative incidence rate of ibrutinib-associated AF was 23% at 12 months and 38% at 2 years. The management of ibrutinib-associated AF is challenging due to difficulties in balancing the benefits of anticoagulation to mitigate the risk of stroke and the bleeding risk associated with ibrutinib. AF is a frequent reason for discontinuation of ibrutinib therapy, and can result in significant morbidity. In addition to this arrhythmogenic effect, ibrutinib is also significantly associated with the onset or worsening of arterial hypertension. Finally, an increased risk of serious ventricular rhythm disorders has also been suggested by pharmacovigilance databases, but not yet confirmed by prospective clinical studies. The study proposes a comprehensive cardiovascular approach, at baseline and during follow-up of patients on Ibrutinib, using innovative markers to anticipate patients most at risk of developing these cardiovascular effects, but also to detect them as early as possible in order to avoid the complications they may generate.

Conditions

Ibrutinib Treatment

Outcome Measures

Primary Outcomes (1)

• rate of patients developing atrial fibrillation (AF)

  Compare the values of selected biomarkers between patients who have developed AF and patients without AF

  12 months after introduction of ibrutinib

Study Arms (1)

patient

Patients with an indication for ibrutinib treatment for hematologic reasons

Other: ophthalmological examination; Biological: blood test

Interventions

ophthalmological examination OTHER

OCT-retinal angiography At inclusion, 3 months and 6 months

patient

blood test BIOLOGICAL

a 2-mL tube of blood will be taken to test for blood markers predisposing to cardiovascular complications. At inclusion

patient

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

Eligible patients will be identified by a doctor working in the hematology department of Dijon University Hospital during his or her regular medical check-up.

You may qualify if:

• Patients with an indication for ibrutinib treatment for hematologic reasons
• Patients aged 18 and over
• Patients who have given their free, written and informed consent to this study after being informed (or by the patient's representative if the patient is unable to express his or her consent).

You may not qualify if:

• Person not affiliated to national health insurance
• Patient under legal protection (curatorship, guardianship)
• Patient subject to a safeguard of justice measure
• Pregnant, parturient or breast-feeding women
• Previous treatment with ibrutinib
• Follow-up planned in another center
• History of atrial fibrillation

Sponsors & Collaborators

• Centre Hospitalier Universitaire Dijon: lead

Study Sites (1)

Chu Dijon Bourgogne

Dijon, 21000, France

Location

MeSH Terms

Interventions

Hematologic Tests

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Design

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

Study Record Dates

• First Submitted: July 3, 2023
• First Posted: July 11, 2023
• Study Start: December 20, 2023
• Primary Completion: August 5, 2025
• Study Completion: August 5, 2025
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

FR (1)