Chronic Ibrutinib Therapy Effect on Left Atrial Function (CITE-LA)

October 13, 2023 updated by: Ivan Zeljkovic, University Hospital "Sestre Milosrdnice"

Long-term Effect of Chronic Ibrutinib Therapy on Left Atrial Function

Ibrutinib is an irreversible Bruton tyrosine-kinase inhibitor. In prospective studies, the ibrutinib efficacy in the treatment of various B-cell malignancies was established. Different ibrutinib side-effects have been found: diarrhea, arthralgia, infections, neutropenia, hypertension and increased risk of bleeding. Most of the mentioned side-effects were <3rd degree of severity and mostly didn't require dose adjustment or therapy discontinuation. Also, there was an increase in the incidence of atrial fibrillation (AFib) (6-16%). The AFib pathogenesis in this patient population is not clarified, but there are indications that ibrutinib inhibits phosphoinositide-3-kinase (PI3K)-Akt signal-pathway expressed in the myocytes. Regardless of the molecular pathogenesis, the clinical effect of ibrutinib on the myocardium, especially the left atrium, has not been studied. Hence, the aim of this study is to determine the ibrutinib effect on echocardiographic parameters of left atrial function.

This study will be performed as a clinical, prospective, observational cohort study with a structured follow-up period of 12 months. All consecutive patients with hemato-oncologic diseases (including chronic lymphocytic leukemia, Mantle-cell lymphoma, Waldenstrom macroglobulinemia, etc.) prescribed with chronic ibrutinib therapy, who are able to understand and sign informed consent, will be enrolled. Primary objective is change of the left atrial function measured by the decrease of the left atrial strain deformation > 10%.

Recruiting should not exceed 12 months with the minimal follow-up period of 12 months (24 months in total). Standardized statistical methods and tests will be done using SPSS Version 22.0 or newer.

This unique study offers the possibility to show the long-term effect of chronic ibrutinib therapy on left atrial function assessed by transthoracic echocardiography. This observational data is needed to further refine the treatment of these patients and to prevent possible side-effects of ibrutinib which could endanger this specific patient population.

Study Overview

Status

Completed

Conditions

Study Type

Observational

Enrollment (Actual)

40

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Croatia
      • Zagreb, Croatia, 10000
        • Sestre milosrdnice University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

All consecutive patients with haemato-oncologic diseases (including chronic lymphocytic leukemia, Mantle-cell lymphoma, Waldenstrom macroglobulinaemia) prescribed with chronic ibrutinib therapy, who are able to understand and sign informed consent, will be enrolled.

Description

Inclusion Criteria:

  • patients with haemato-oncologic diseases (including chronic lymphocytic leukemia, Mantle-cell lymphoma, Waldenstrom macroglobulinaemia, etc.)
  • patients prescribed with chronic ibrutinib therapy
  • patients who are able to understand and sign informed consent

Exclusion Criteria:

  • patients with haemato-oncologic diseases who were prescribed with concomitant chemotherapy which can impact left atrial function
  • patients < 18 years old
  • patients with known or at initial echocardiography established dilated cardiomyopathy with left ventricular ejection fraction < 35%
  • patients with permanent atrial fibrillation and dilated left atrium or dilated both atriums
  • patients implanted with cardiac implantable electronic devices
  • patients who underwent cardiac surgery
  • patients with congenital heart diseases (surgically corrected or not)
  • patients with severe valvular pathology
  • patients with terminal renal disease
  • patients with chronic obstructive pulmonary disease - GOLD grade 4
  • patients with life expectancy < 12 months
  • patients not willing to undergo clinical follow-up or sign informed consent
  • patients recruited in another clinical study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
left atrial function change
Time Frame: initial measurement, 3 months, 6 months and 12 months after initiation of ibrutinib therapy
change of the left atrial function measured by the decrease of the left atrial strain deformation > 10% assessed by transthoracic echocardiography
initial measurement, 3 months, 6 months and 12 months after initiation of ibrutinib therapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
left ventricular ejection fraction change
Time Frame: initial measurement, 3 months, 6 months and 12 months after initiation of ibrutinib therapy
measurement of left ventricular systolic function change assessed by transthoracic echocardiography - method according to Simpson and Teicholz
initial measurement, 3 months, 6 months and 12 months after initiation of ibrutinib therapy
left ventricular diastolic function change
Time Frame: initial measurement, 3 months, 6 months and 12 months after initiation of ibrutinib therapy
measurement of left ventricular diastolic function change assessed by transthoracic echocardiography (E/A and E/E')
initial measurement, 3 months, 6 months and 12 months after initiation of ibrutinib therapy
left atrial volume change
Time Frame: initial measurement, 3 months, 6 months and 12 months after initiation of ibrutinib therapy
2D and 3D left atrial volume change assessed by transthoracic echocardiography + left atrial dimension in PLAX and 4 chamber projection
initial measurement, 3 months, 6 months and 12 months after initiation of ibrutinib therapy
P wave duration change
Time Frame: initial measurement, 3 months, 6 months and 12 months after initiation of ibrutinib therapy
P wave duration and PQ interval duration change assessed in 12-lead electrocardiogram (in milliseconds)
initial measurement, 3 months, 6 months and 12 months after initiation of ibrutinib therapy
left atrial pump function change
Time Frame: initial measurement, 3 months, 6 months and 12 months after initiation of ibrutinib therapy
left atrial ejection fractionchange assessed by transthoracic echocardiography (doppler strain measurement method)
initial measurement, 3 months, 6 months and 12 months after initiation of ibrutinib therapy
atrial fibrillation incidence
Time Frame: initial measurement, 3 months, 6 months and 12 months after initiation of ibrutinib therapy
incidence of paroxysmal atrial fibrillation assessed by symptoms + ECG or 24-hours Holter-ECG
initial measurement, 3 months, 6 months and 12 months after initiation of ibrutinib therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital "Sestre Milosrdnice"

Investigators

  • Principal Investigator: Matea Kolacevic, MD, University Hospital "Sestre Milosrdnice"

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2018

Primary Completion (Actual)

March 4, 2023

Study Completion (Actual)

March 4, 2023

Study Registration Dates

First Submitted

November 19, 2018

First Submitted That Met QC Criteria

November 20, 2018

First Posted (Actual)

November 23, 2018

Study Record Updates

Last Update Posted (Actual)

October 17, 2023

Last Update Submitted That Met QC Criteria

October 13, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • UHS-2
  • U1111-1221-9732 (Other Identifier: Universal Trial Number - World Health Organization)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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