AV Junction Ablation or Optimal Medical Treatment in PatiEnts With Cardiac Resynchronization Therapy and Permanent Atrial Fibrillation

Persistent Atrial Fibrillation Clinical Trial

— AMPER-AF  

Official title:

AV Junction Ablation or Optimal Medical Treatment in PatiEnts With Cardiac Resynchronization Therapy and Permanent Atrial Fibrillation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05776797
• Other study ID #: AMPER-AF trial
• Status: Recruiting
• Phase: N/A
• Start date: April 1, 2023
• Est. completion date: March 31, 2029

Study information

• Verified date: June 2023
• Source: University Hospital Ostrava
• Contact: Jirí Hyncica
• Phone: 0042059737
• Email: jiri.hyncica[@]fno.cz
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A study comparing atrioventricular junction ablation (AVJA) versus continued optimum medical rate control in patients with cardiac resynchronization therapy (CRT) and atrial fibrillation (AF) with suboptimal heart rate control on optimum medication.

Description:

Patients fulfilling the enrolment criteria will be randomly (randomization with variable blocks of 4, 6, and 8 patients) allocated to intervention and control groups in a 1:1 ratio. AVJA will be done in patients belonging to the intervention group without undue delay after the randomization. The procedure will be repeated in case of recovery of AV nodal conduction during the trial.

CRT device will be programmed to a base rate of 70 bpm, hysteresis switched off, and rate response functions activated unless not tolerated by the patient. The triggered mode will be encouraged.

All patients will be regularly followed in outpatient clinics. Cross-over to the AVJA study arm will be considered and performed at any time during the trial at the discretion of the operators. This may particularly concern patients with clinical deterioration in terms of functional status, quality of life, systolic left ventricular function, and/or repeated hospitalization, and in whom biventricular pacing (BiVP%) <<100% could be suspected as a significant underlying factor.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 480
• Est. completion date: March 31, 2029
• Est. primary completion date: December 31, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Treatment with CRT using either a biventricular pacemaker/defibrillator or conduction system pacemaker (>6 months)

• Diagnosis of AF and classified as: permanent AF or recurrent persistent AF, requiring emergency visits and/or hospitalizations (at least one in recent year)

• Optimized HF medical treatment and rate control medication

• BiVP% + ventricular premature complex (VPC%) <99% and >85% during the minimum period of 1 month while already on optimum medical therapy (applicable only for patients with permanent AF)

• Age >18 and <85 years

• Signed informed consent

Exclusion Criteria:

• myocardial infarction (MI) or coronary artery bypass graft (CABG) <3 months

• Technical failure of the CRT system

• Intentional preference for spontaneous AV conduction

• Expected survival <1 year

• Other significant comorbidities and/or conditions that interfere with the proper conduction of the trial

• Dementia as assessed by mini-mental test (<23 points)

Related Conditions & MeSH terms

• Atrial Fibrillation
• Persistent Atrial Fibrillation
• Recurrent Atrial Fibrillation

Intervention

Procedure:
• Atrioventricular junction ablation in patients with cardiac resynchronization therapy (CRT)
Ablation of the atrioventricular (AV) node is a procedure used to disrupt or break the electrical connection between the upper heart chambers (the atria) and the lower heart chambers (the ventricles).

Drug:
• Optimal medication treatment in patients with cardiac resynchronization therapy (CRT)
Optimal medication therapy according to the prescription of the physician.

Locations

Country	Name	City	State
Czechia	St. Anne's University Hospital Brno	Brno	South Moravian Region
Czechia	University Hospital Brno	Brno	South Moravian Region
Czechia	Hospital Ceské Budejovice	Ceské Budejovice	South Bohemian Region
Czechia	Regional Hospital Liberec	Liberec	Liberec Region
Czechia	University Hospital Olomouc	Olomouc	Olomouc Region
Czechia	University Hospital Ostrava	Ostrava	Moravian-Silesian Region
Czechia	Institute of Clinical and Experimental Medicine	Prague
Czechia	Military University Hospital Prague	Prague
Czechia	Hospital Podlesí, Inc.	Trinec	Moravian-Silesian Region

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Ostrava

Country where clinical trial is conducted

Czechia, 

References & Publications (11)

Bozkurt B, Coats AJS, Tsutsui H, Abdelhamid CM, Adamopoulos S, Albert N, Anker SD, Atherton J, Bohm M, Butler J, Drazner MH, Michael Felker G, Filippatos G, Fiuzat M, Fonarow GC, Gomez-Mesa JE, Heidenreich P, Imamura T, Jankowska EA, Januzzi J, Khazanie P, Kinugawa K, Lam CSP, Matsue Y, Metra M, Ohtani T, Francesco Piepoli M, Ponikowski P, Rosano GMC, Sakata Y, Seferovic P, Starling RC, Teerlink JR, Vardeny O, Yamamoto K, Yancy C, Zhang J, Zieroth S. Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure: Endorsed by the Canadian Heart Failure Society, Heart Failure Association of India, Cardiac Society of Australia and New Zealand, and Chinese Heart Failure Association. Eur J Heart Fail. 2021 Mar;23(3):352-380. doi: 10.1002/ejhf.2115. Epub 2021 Mar 3. — View Citation

Dong K, Shen WK, Powell BD, Dong YX, Rea RF, Friedman PA, Hodge DO, Wiste HJ, Webster T, Hayes DL, Cha YM. Atrioventricular nodal ablation predicts survival benefit in patients with atrial fibrillation receiving cardiac resynchronization therapy. Heart Rhythm. 2010 Sep;7(9):1240-5. doi: 10.1016/j.hrthm.2010.02.011. Epub 2010 Feb 13. — View Citation

Ganesan AN, Brooks AG, Roberts-Thomson KC, Lau DH, Kalman JM, Sanders P. Role of AV nodal ablation in cardiac resynchronization in patients with coexistent atrial fibrillation and heart failure a systematic review. J Am Coll Cardiol. 2012 Feb 21;59(8):719-26. doi: 10.1016/j.jacc.2011.10.891. — View Citation

Glikson M, Nielsen JC, Kronborg MB, Michowitz Y, Auricchio A, Barbash IM, Barrabes JA, Boriani G, Braunschweig F, Brignole M, Burri H, Coats AJS, Deharo JC, Delgado V, Diller GP, Israel CW, Keren A, Knops RE, Kotecha D, Leclercq C, Merkely B, Starck C, Thylen I, Tolosana JM; ESC Scientific Document Group. 2021 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy. Eur Heart J. 2021 Sep 14;42(35):3427-3520. doi: 10.1093/eurheartj/ehab364. No abstract available. Erratum In: Eur Heart J. 2022 May 1;43(17):1651. — View Citation

Huber A, Oldridge N, Hofer S. International SF-36 reference values in patients with ischemic heart disease. Qual Life Res. 2016 Nov;25(11):2787-2798. doi: 10.1007/s11136-016-1316-4. Epub 2016 Jun 18. — View Citation

Hussain A, Misra A, Bozkurt B. Endpoints in Heart Failure Drug Development. Card Fail Rev. 2022 Jan 18;8:e01. doi: 10.15420/cfr.2021.13. eCollection 2022 Jan. — View Citation

Koplan BA, Kaplan AJ, Weiner S, Jones PW, Seth M, Christman SA. Heart failure decompensation and all-cause mortality in relation to percent biventricular pacing in patients with heart failure: is a goal of 100% biventricular pacing necessary? J Am Coll Cardiol. 2009 Jan 27;53(4):355-60. doi: 10.1016/j.jacc.2008.09.043. — View Citation

Levy WC, Mozaffarian D, Linker DT, Sutradhar SC, Anker SD, Cropp AB, Anand I, Maggioni A, Burton P, Sullivan MD, Pitt B, Poole-Wilson PA, Mann DL, Packer M. The Seattle Heart Failure Model: prediction of survival in heart failure. Circulation. 2006 Mar 21;113(11):1424-33. doi: 10.1161/CIRCULATIONAHA.105.584102. Epub 2006 Mar 13. — View Citation

Ousdigian KT, Borek PP, Koehler JL, Heywood JT, Ziegler PD, Wilkoff BL. The epidemic of inadequate biventricular pacing in patients with persistent or permanent atrial fibrillation and its association with mortality. Circ Arrhythm Electrophysiol. 2014 Jun;7(3):370-6. doi: 10.1161/CIRCEP.113.001212. Epub 2014 May 17. — View Citation

Packer M. Development and Evolution of a Hierarchical Clinical Composite End Point for the Evaluation of Drugs and Devices for Acute and Chronic Heart Failure: A 20-Year Perspective. Circulation. 2016 Nov 22;134(21):1664-1678. doi: 10.1161/CIRCULATIONAHA.116.023538. — View Citation

Waranugraha Y, Rizal A, Setiawan D, Aziz IJ. The Benefit of Atrioventricular Junction Ablation for Permanent Atrial Fibrillation and Heart Failure Patients Receiving Cardiac Resynchronization Therapy: An Updated Systematic Review and Meta-analysis. Indian Pacing Electrophysiol J. 2021 Mar-Apr;21(2):101-111. doi: 10.1016/j.ipej.2020.12.005. Epub 2021 Feb 4. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Heart failure (HF) events	The number of HF events will be observed.	3 years
Primary	36-Item Quality of Life (QoL)	QoL will be assessed using the 36-Item Quality of Life Questionnaire. QoL will be evaluated at 12, 24 and 36 months as a sum of points that are assigned to individual outcome measures, specifically to their change compared to the baseline.; To score the SF-36, scales are standardized to obtain a score ranging from 0 to 100. Higher scores indicate better health status, and a mean score of 50 has been articulated as a normative value for all scales.	3 years
Primary	Minnesota Living with Heart Failure Questionnaire (MLHFQ)	MLHFQ values will be recorded and evaluated at 12, 24 and 36 months. The questionnaire is comprised of 21 questions around several physical, emotional and socioeconomic ways heart failure can adversely affect a patient's life. The patient marks a 0 (zero) to 5 (five) scale to indicate the extent to which each itemized adversity of heart failure has prevented the patient from living as they wanted to live during the past 4 weeks. The questionnaire is simply scored by summation of all 21 responses.	3 years
Primary	Dose of loop diuretics	Change in the dose of loop diuretics will be observed and recorded. This parameter will be evaluated at 12, 24 and 36 months as an increase or decrease of the dose compared to the baseline.	3 years
Primary	NYHA classification	Changes in the New York Heart Association classification (NYHA) will be observed. The NYHA classification values will be evaluated at 12, 24 and 36 months. The New York Heart Association (NYHA) Classification provides a simple way of classifying the extent of heart failure. It classifies patients in one of four categories based on their limitations during physical activity; the limitations/symptoms are in regards to normal breathing and varying degrees in shortness of breath and or angina pain.	3 years
Secondary	All-cause death	Patient deaths from all causes will be observed, recorded and analysed.	3 years
Secondary	Death from cardiovascular diseases (CV death)	Incidents of CV death will be observed, recorded and analysed.	3 years
Secondary	Combined heart failure (HF) death and HF hospitalization	Incidents of combined heart failure (HF) death and HF hospitalization will be observed, recorded and analysed.	3 years
Secondary	Time-averaged proportional change in NT-pro-Brain Natriuretic Peptide (NT-pro-BNP)	The time-averaged proportional change in NT-pro-BNP will be observed, recorded and analysed.	3 years
Secondary	Days in the hospital because of heart failure (HF)	The number of days in the hospital because of heart failure (HF) will be recorded.	3 years
Secondary	Time-averaged change in the NYHA class	The time-averaged change in the NYHA class will be observed, recorded and analysed.	3 years