Clinical trial NCT05540600: Left Atrium Reservoir Function Modulation in Patients With Atrial Fibrillation: Digoxin Versus Beta Blocker
Official title: Left Atrium Reservoir Function Modulation in Patients With Atrial Fibrillation: A Randomized Digoxin Versus Beta Blocker Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Atrial Fibrillation
Left Atrial Rhythm
Lead sponsor: University of Monastir
Sponsor class: OTHER
First posted: 2022-09-14
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: ß blocker and digoxin effect on left atrium reservoir function are unknown. This is a randomized open label study to compare the effect of theses two molecules on left atrium function

Detailed description: Atrial fibrillation (AF) is responsible of significant morbidity and mortality. Management of signs and symptoms of heart failure generated by AF is at the center of the latest European recommendations . Mechanisms by which these symptoms are generated are very poorly understood. Heart rate control is one of the recommended strategies but remains poorly codified and generally follows the preferences and experiences of each local center. The European guidelines propose at least 4 molecules for heart rate control without emitting preferences for one molecule over the other due to the lack of robust randomized studies. Recently, a study comparing digoxin vs ß-blockers showed the superiority of digoxin in decreasing symptoms despite a comparable action on heart rate. On the other hand, the reservoir function of the left atrium (LA) has taken a central role in assessing signs of left heart failure and monitoring filling pressures . Other studies have demonstrated the association of left atrium reservoir strain with these symptoms .

It is commonly accepted that ß blockers decrease AF-related symptoms by a negative chronotropic effect thanks to their blocking action on the sympathetic system. While the action of digoxin on symptoms goes through a positive inotropic effect thanks to the increase in intracellular calcium .

However, the impact of these two molecules on the function of the left atrium has never been investigated. Our diagnostic hypothesis is that in addition to their action on heart rate, the improvement of symptoms noted by using b blockers and digoxin during the treatment of AF would go through an improvement LA reservoir function . The superiority of digoxin in the reduction of symptoms compared to ß blockers would be due to a greater improvement in reservoir function and this thanks to the increase in myocardial intracellular calcium.

Eligibility criteria: Inclusion Criteria:

* Any patient with atrial fibrillation naïve to ß-blocker and digoxin or patients followed for Atrial fibrillation and discontinued all treatment for more than a week.
* Frequency Control Strategy Decided
* Age over 18 years
* Stable hemodynamic state
* No contraindication to digoxin or ß-blocker

Exclusion Criteria:

* Required rhythm control strategy
* Contraindication to one of the two
* Heart rate \<60 BPM
* Clearance rénale \<30 ml/mn
* Pregnant or breastfeeding woman
* Persistence of a resting heart rate \> 110
* Severe comorbidity with decreased life expectancy (advanced neoplasia, large stroke...)

Primary outcomes:
measure: Left atrium reservoir strain before and after treatment
timeFrame: 4 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Monastir
country: Tunisia
facility: Fattouma Bourguiba University hospital
Study officials:
affiliation: Monastir university
name: Nidhal Bouchahda, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kotecha D, Bunting KV, Gill SK, Mehta S, Stanbury M, Jones JC, Haynes S, Calvert MJ, Deeks JJ, Steeds RP, Strauss VY, Rahimi K, Camm AJ, Griffith M, Lip GYH, Townend JN, Kirchhof P; Rate Control Therapy Evaluation in Permanent Atrial Fibrillation (RATE-AF) Team. Effect of Digoxin vs Bisoprolol for Heart Rate Control in Atrial Fibrillation on Patient-Reported Quality of Life: The RATE-AF Randomized Clinical Trial. JAMA. 2020 Dec 22;324(24):2497-2508. doi: 10.1001/jama.2020.23138.
citation: Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castella M, Diener HC, Heidbuchel H, Hendriks J, Hindricks G, Manolis AS, Oldgren J, Popescu BA, Schotten U, Van Putte B, Vardas P, Agewall S, Camm J, Baron Esquivias G, Budts W, Carerj S, Casselman F, Coca A, De Caterina R, Deftereos S, Dobrev D, Ferro JM, Filippatos G, Fitzsimons D, Gorenek B, Guenoun M, Hohnloser SH, Kolh P, Lip GY, Manolis A, McMurray J, Ponikowski P, Rosenhek R, Ruschitzka F, Savelieva I, Sharma S, Suwalski P, Tamargo JL, Taylor CJ, Van Gelder IC, Voors AA, Windecker S, Zamorano JL, Zeppenfeld K. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur J Cardiothorac Surg. 2016 Nov;50(5):e1-e88. doi: 10.1093/ejcts/ezw313. Epub 2016 Sep 23. No abstract available.
citation: Ziff OJ, Kotecha D. Digoxin: The good and the bad. Trends Cardiovasc Med. 2016 Oct;26(7):585-95. doi: 10.1016/j.tcm.2016.03.011. Epub 2016 Mar 31.
citation: Badano LP, Kolias TJ, Muraru D, Abraham TP, Aurigemma G, Edvardsen T, D'Hooge J, Donal E, Fraser AG, Marwick T, Mertens L, Popescu BA, Sengupta PP, Lancellotti P, Thomas JD, Voigt JU; Industry representatives; Reviewers: This document was reviewed by members of the 2016-2018 EACVI Scientific Documents Committee. Standardization of left atrial, right ventricular, and right atrial deformation imaging using two-dimensional speckle tracking echocardiography: a consensus document of the EACVI/ASE/Industry Task Force to standardize deformation imaging. Eur Heart J Cardiovasc Imaging. 2018 Jun 1;19(6):591-600. doi: 10.1093/ehjci/jey042.