Clinical trial NCT05939752: Cardiovascular Complications of Ibrutinib Therapy
Official title: Cardiovascular Complications of Ibrutinib Therapy: a Single-center Cohort Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Ibrutinib Treatment
Lead sponsor: Centre Hospitalier Universitaire Dijon
Sponsor class: OTHER
First posted: 2023-07-11
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.


Eligibility criteria: Inclusion Criteria:

* 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).

Exclusion Criteria:

* 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

Primary outcomes:
measure: rate of patients developing atrial fibrillation (AF)
timeFrame: 12 months after introduction of ibrutinib
Secondary outcomes:
Other outcomes:
Locations:
city: Dijon
country: France
facility: Chu Dijon Bourgogne
Study officials:
References: