Left Atrium Reservoir Function Modulation in Patients With Atrial Fibrillation: Digoxin Versus Beta Blocker

Atrial Fibrillation Clinical Trial

Official title:

Left Atrium Reservoir Function Modulation in Patients With Atrial Fibrillation: A Randomized Digoxin Versus Beta Blocker Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05540600
• Other study ID #: TN2022-NAT-I NS-86
• Status: Recruiting
• Phase: Phase 3
• Start date: September 12, 2022
• Est. completion date: December 1, 2023

Study information

• Verified date: September 2022
• Source: University of Monastir
• Contact: Nidhal Bouchahda, MD
• Phone: +21696755261
• Email: nidhalbouchahda[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 1, 2023
• Est. primary completion date: January 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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...)

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Drug:
• Digoxin 0.25 mg
Patients will have the dose of one tablet of 0.25mg per day
• Bisoprolol
Patients will have the dose of bisoprolol 2.5 mg or 5 mg twice a day based on the arterial pressure at randomization

Locations

Country	Name	City	State
Tunisia	Fattouma Bourguiba University hospital	Monastir

Sponsors (1)

Lead Sponsor	Collaborator
University of Monastir

Country where clinical trial is conducted

Tunisia, 

References & Publications (4)

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. Review. Erratum in: Eur Heart J Cardiovasc Imaging. 2018 Jul 1;19(7):830-833. — View 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. Epub 2016 Sep 23. — View 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. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Left atrium reservoir strain before and after treatment	Measurements of Left atrium reservoir strain will be performed at randomization and after 4 weeks on 4 chambers and 2 chamber views according to the most recent recommendations. The acquisition of strain-2D curves will be made by taking as a reference the beginning of the QRS complex. The peak of the curve corresponds to the value of the reservoir strain of the left atrium	4 weeks