Cryoballoon/Radiofrequency/Pulsed Field Ablation of Atrial Fibrillation Versus Medical Treatment for Heart

NCT06505798 | Recruiting DMC

• 4 other identifiers: 136905CS/F/21/190034 CRAAFT-HF28114224/LO/0301
• Study Type: interventional
• Target: 1,200
• Locations: 2 countries
• Sites: 24

Brief Summary

Atrial fibrillation (AF) is a common heart rhythm disorder that causes an irregular heart beat and is a cause of heart failure (HF). Treatments include drugs to slow the heart rate, anti-arrhythmic drugs or ablation of the heart to help preserve normal rhythm. A number of trials have suggested that ablation may be superior to drug treatment to reduce hospitalisations or prevent early death. However, these studies have been small and the results not applicable to the general population with AF and heart failure in the UK. This international study will compare catheter ablation and optimal medical therapy versus optimal medical therapy alone to see if catheter ablation reduces unplanned heart failure hospitalisations and death rates and improves quality of life.

Conditions

Atrial Fibrillation (AF)

Keywords

AF

Outcome Measures

Primary Outcomes (1)

• Time to first all-cause death and urgent CV hospitalisation

  The primary outcome (time to first all-cause death and urgent CV hospitalisation) will be summarised by randomised group and analysed using a Cox proportional hazards regression model for time to first event, adjusting for factors used to balance the randomisation.

  2 years minimum (range: 2-5.5 years)

Secondary Outcomes (5)

• Total (first and recurrent) all-cause death and urgent cardiovascular hospitalisations.

  2 years minimum (range: 2-5.5 years)

• QoL at 6 and 12 months assessed using the KCCQ-CSS.

  12 months

• Time to all-cause death

  2 years minimum (range: 2-5.5 years)

• Total (first and recurrent) all-cause death and urgent HF hospitalisations

  2 years minimum (range: 2-5.5 years)

• Cardiovascular death

  2 years minimum (range: 2-5.5 years)

Study Arms (2)

The optimal medical therapy as per standard of care

NO INTERVENTION

Participants randomised to the optimal medical therapy arm will receive optimal medical therapy according to the most contemporary ESC HF guidelines.

The catheter ablation

OTHER

Catheter ablation is an established therapeutic strategy in patients without HF that aims to convert AF to sinus rhythm in symptomatic, drug-refractory AF in patients.

Procedure: Catheter Ablation

Interventions

Catheter Ablation PROCEDURE

Participants randomised to the catheter ablation arm will undergo Pulmonary Vein Isolation (PVI) which is the essential ablation intervention. The technique used will be at the discretion of the treating physician but may include Cryoballoon (Medtronic/Boston Scientific), Radiofrequency: CARTO (Biosense), pulsed field radiofrequency ablation, or Precision (Abbott Medical) electro-anatomical mapping systems. Additional ablation lesions may be delivered as preferred by the operator and will be documented. Electro-anatomical voltage maps will be collected (in SR/AF) and stored for later analysis.

The catheter ablation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged ≥18 years.
• Patient is willing and able to give informed consent for participation.
• Able and willing to comply with all study requirements, including ability to participate in study for 12 months.
• Willing to allow their General Practitioner (GP) to be notified of participation in the study.
• Patient with one of the following AF categories and at least one episode of AF documented (by any means eg ECG, Holter, Cardiac Implantable Electronic Device (CIED) interrogation or any other means):
• Paroxysmal AF defined as spontaneous self-terminating AF lasted \> 6 hours and \<7 days.
• Persistent AF as defined by at least one episode of AF \>7 days but not \>3 years (since 1st documentation)
• Optimal tolerated medical therapy for HF (including ACE-I (or ARB or ARNi), beta-blocker, SGLT2 inhibitor and mineralocorticoid receptor antagonist (MRA) and cardiac resynchronisation therapy (CRT) where indicated \& tolerated) for at least 6 weeks (according to the most contemporary European Society of Cardiology (ESC) HF guidelines). Maximal doses of these drugs are not mandated.
• New York Heart Association Classification (NYHA) class II to III
• LVEF \<50% (Cardiac imaging report of LVEF\<50% within 1 year (by echocardiography, cardiac magnetic resonance imaging or nuclear cardiology assessment)) AND after optimisation of medical therapy (see previous definition). Note - a LVEF of \<50% must be documented by any cardiac imaging performed after optimisation of medical therapy. Documentation of other baseline echocardiographic parameters (eg LA volume, E/E' etc can be obtained from any echocardiogram within 2.5 years). This allows a handheld or echocardiogram focused on LVEF assessment.
• For those with LVEF 41-49% and without ongoing atrial fibrillation/flutter, N-terminal pro B-type natriuretic peptide (NT-proBNP) of ≥300pg/mL is required within 12 months prior to randomisation.
• For those with LVEF 41-49% and with ongoing atrial fibrillation/flutter, NTproBNP of ≥600pg/mL is required within 12 months prior randomisation.
• For those with LVEF ≤40%, NTproBNP is not required

You may not qualify if:

• Long standing (\>3 year) persistent or permanent AF.
• Previous atrioventricular (AV) nodal ablation.
• Previous pulmonary vein isolation (PVI) or surgical ablation.
• Severe aortic or pulmonary valve disease.
• Severe primary or secondary mitral valve regurgitation.
• Active illness (other than HF) likely to result in death within 2 years.
• People who are pregnant or planning to become pregnant during the trial.
• People who are breastfeeding.
• Known allergy to contrast.
• Contraindication for PVI.
• Other conditions that may prevent subjects from adhering to the trial protocol, in the opinion of the investigator.
• Currently participating in another randomised controlled trial of another drug or medical device.

Sponsors & Collaborators

• University College, London: lead

Study Sites (24)

Halifax Infirmary

Halifax, Canada

RECRUITING

Mid and South Essex NHS Foundation Trust

Basildon, United Kingdom

RECRUITING

Queen Elizabeth Hospital

Birmingham, United Kingdom

RECRUITING

Blackpool Victoria Hospital

Blackpool, United Kingdom

RECRUITING

University Hospitals Dorset NHS Foundation Trust

Bournemouth, United Kingdom

RECRUITING

Royal Papworth Hospital NHS Foundation Trust

Cambridge, CB2 0AY, United Kingdom

RECRUITING

University Hospitals Coventry and Warwickshire NHS Trust

Coventry, United Kingdom

RECRUITING

Golden Jubilee National Hospital

Glasgow, G81 4DY, United Kingdom

RECRUITING

Hull University Teaching Hospitals NHS Trust

Hull, United Kingdom

RECRUITING

Leeds Teaching Hospitals NHS Trust

Leeds, United Kingdom

RECRUITING

Glenfield Hospital

Leicester, United Kingdom

RECRUITING

Liverpool Heart and Chest Hospital NHS Foundation Trust

Liverpool, United Kingdom

RECRUITING

Royal Brompton and Harefields Hospitals

London, UB9 6JH, United Kingdom

RECRUITING

Barts Health NHS Trust

London, United Kingdom

RECRUITING

Imperial College Healthcare NHS Trust

London, United Kingdom

RECRUITING

St George's University Hospitals NHS Foundation Trust

London, United Kingdom

RECRUITING

St Thomas' hospital

London, United Kingdom

RECRUITING

James Cook University Hosptial

Middlesbrough, United Kingdom

RECRUITING

Freeman Hospital, Royal Victoria Infirmary

Newcastle, United Kingdom

RECRUITING

Nottingham University Hospital NHS Trust

Nottingham, United Kingdom

RECRUITING

University Hospitals Plymouth NHS Trust

Plymouth, United Kingdom

RECRUITING

Queen Alexandra Hospital

Portsmouth, United Kingdom

RECRUITING

Southampton General

Southampton, United Kingdom

RECRUITING

Swansea Bay University Health Board

Swansea, United Kingdom

RECRUITING

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

Catheter Ablation

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Radiofrequency Ablation; Radiofrequency Therapy; Therapeutics; Ablation Techniques; Surgical Procedures, Operative

Study Officials

• Pier Lambiase

  University College, London

  PRINCIPAL INVESTIGATOR

• Mark Petrie

  University of Glasgow

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pier Lambiase

CONTACT

07977217787; p.lambiase@ucl.ac.uk

CRAAFT-HF Team @ Barts CVCTU

CONTACT

craaft-hf-cvctu@qmul.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a randomised, adaptive open label multicentre clinical trial which compares optimal medical therapy (as per standard of care) with catheter ablation plus optimal medical therapy alone in participants with HfrEF (LVEF\<50%) and paroxysmal or persistent atrial fibrillation. This design is adaptive in that the required sample size is reviewed in an interim analysis at 80% recruitment. This interim analysis aims to ensure that sufficient patients are recruited to maintain the conditional power of the study at 80% or higher. Options which can be deployed at the interim analysis include increasing patient numbers and increasing duration of follow up.

Study Record Dates

• First Submitted: July 1, 2024
• First Posted: July 17, 2024
• Study Start: November 21, 2024
• Primary Completion (Estimated): December 15, 2031
• Study Completion (Estimated): December 15, 2031
• Last Updated: May 4, 2026

Record last verified: 2026-03

Locations

GB (23); CA (1)