Chronic Ibrutinib Therapy Effect on Left Atrial Function

Echocardiography Clinical Trial

— CITE-LA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03751410
• Other study ID #: UHS-2
• Secondary ID: U1111-1221-9732
• Status: Completed
• Start date: December 1, 2018
• Est. completion date: March 4, 2023

Study information

• Verified date: October 2023
• Source: University Hospital "Sestre Milosrdnice"
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: March 4, 2023
• Est. primary completion date: March 4, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atrium; Beat
• Echocardiography
• Physiology
• Therapy Adverse Effect

Locations

Country	Name	City	State
Croatia	Sestre milosrdnice University Hospital	Zagreb

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital "Sestre Milosrdnice"

Country where clinical trial is conducted

Croatia, 

References & Publications (11)

Boriani G, Corradini P, Cuneo A, Falanga A, Foa R, Gaidano G, Ghia PP, Martelli M, Marasca R, Massaia M, Mauro FR, Minotti G, Molica S, Montillo M, Pinto A, Tedeschi A, Vitolo U, Zinzani PL. Practical management of ibrutinib in the real life: Focus on atr — View Citation

Burger JA, Tedeschi A, Barr PM, Robak T, Owen C, Ghia P, Bairey O, Hillmen P, Bartlett NL, Li J, Simpson D, Grosicki S, Devereux S, McCarthy H, Coutre S, Quach H, Gaidano G, Maslyak Z, Stevens DA, Janssens A, Offner F, Mayer J, O'Dwyer M, Hellmann A, Schu — View Citation

Byrd JC, Brown JR, O'Brien S, Barrientos JC, Kay NE, Reddy NM, Coutre S, Tam CS, Mulligan SP, Jaeger U, Devereux S, Barr PM, Furman RR, Kipps TJ, Cymbalista F, Pocock C, Thornton P, Caligaris-Cappio F, Robak T, Delgado J, Schuster SJ, Montillo M, Schuh A, — View Citation

Deeks ED. Ibrutinib: A Review in Chronic Lymphocytic Leukaemia. Drugs. 2017 Feb;77(2):225-236. doi: 10.1007/s40265-017-0695-3. — View Citation

Kaur V, Swami A. Ibrutinib in CLL: a focus on adverse events, resistance, and novel approaches beyond ibrutinib. Ann Hematol. 2017 Jul;96(7):1175-1184. doi: 10.1007/s00277-017-2973-2. Epub 2017 Mar 24. — View Citation

Leong DP, Caron F, Hillis C, Duan A, Healey JS, Fraser G, Siegal D. The risk of atrial fibrillation with ibrutinib use: a systematic review and meta-analysis. Blood. 2016 Jul 7;128(1):138-40. doi: 10.1182/blood-2016-05-712828. Epub 2016 May 31. No abstrac — View Citation

Mato AR, Clasen S, Pickens P, Gashonia L, Rhodes J, Svoboda J, Hughes M, Nabhan C, Ali N, Schuster S, Carver J. Left atrial abnormality (LAA) as a predictor of ibrutinib-associated atrial fibrillation in patients with chronic lymphocytic leukemia. Cancer — View Citation

O'Brien S, Hillmen P, Coutre S, Barr PM, Fraser G, Tedeschi A, Burger JA, Dilhuydy MS, Hess G, Moreno C, Cramer P, Liu E, Chang S, Vermeulen J, Styles L, Howes A, James DF, Patel K, Graef T, Valentino R. Safety Analysis of Four Randomized Controlled Studi — View Citation

Reda G, Fattizzo B, Cassin R, Mattiello V, Tonella T, Giannarelli D, Massari F, Cortelezzi A. Predictors of atrial fibrillation in ibrutinib-treated CLL patients: a prospective study. J Hematol Oncol. 2018 Jun 11;11(1):79. doi: 10.1186/s13045-018-0626-0. — View Citation

Thompson PA, Burger JA. Bruton's tyrosine kinase inhibitors: first and second generation agents for patients with Chronic Lymphocytic Leukemia (CLL). Expert Opin Investig Drugs. 2018 Jan;27(1):31-42. doi: 10.1080/13543784.2018.1404027. Epub 2017 Nov 15. — View Citation

Wierda WG, Zelenetz AD, Gordon LI, Abramson JS, Advani RH, Andreadis CB, Bartlett N, Byrd JC, Caimi P, Fayad LE, Fisher RI, Glenn MJ, Habermann TM, Harris NL, Hernandez-Ilizaliturri F, Hoppe RT, Horwitz SM, Kaminski MS, Kelsey CR, Kim YH, Krivacic S, LaCa — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	left atrial function change	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	left ventricular ejection fraction change	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
Secondary	left ventricular diastolic function change	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
Secondary	left atrial volume change	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
Secondary	P wave duration change	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
Secondary	left atrial pump function change	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
Secondary	atrial fibrillation incidence	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