Cryoballoon/Radiofrequency/Pulsed Field Ablation of Atrial Fibrillation Versus Medical Treatment for Heart (CRAAFT-HF)

April 28, 2026 updated by: University College, London
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Atrial fibrillation (AF) increases the severity of, and death from, heart failure (HF). Several small studies have demonstrated that restoration of sinus rhythm by catheter ablation in patients with HF improves left ventricular (LV) function and exercise tolerance. What is unknown is whether or not AF ablation reduces all-cause death and urgent CV hospitalisations in populations with HF. The current trial will answer this outstanding question, which is faced by HF clinicians and electrophysiologists on a daily basis. AF ablation can be performed very effectively and efficiently using a cryo-balloon or radio-frequency ablation PVI technique. These techniques have evolved slowly and are unlikely to change substantially over the course of this trial. One small trial (n=363) in implantable cardioverter-defibrillator and CRT defibrillator recipients (CASTLE-AF) reported a death benefit of AF ablation but the patients were highly selected and the death reduction was far higher than real world expected differences. Recent studies have noted that the population randomised in CASTLE-AF was not representative of the general HF population with only 7% of patients in the "real world" setting meeting the trial entry criteria. CASTLE-AF is therefore provocative but inconclusive; it has made little change to clinical practice. As no studies have investigated the death benefit in a general HF population, the proposed trial is necessary and warranted. This study is designed as a randomised, open label multicentre clinical trial in which catheter ablation and medical therapy is compared to medical therapy alone in patients with HF with reduced ejection fraction (<50%) and paroxysmal or persistent AF to determine if this reduces all-cause death and urgent CV hospitalisations as well as improving QoL. By utilising the clinical and research networks of the British Heart Failure Society and British Heart Rhythm Society (BHRS) we will recruit 1200 patients. The current trial will be almost three times the size of the only previous inconclusive trial which was reported in the New England Journal of Medicine.

Study Type

Interventional

Enrollment (Estimated)

1200

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
  • United Kingdom
      • Basildon, United Kingdom
        • Recruiting
        • Mid and South Essex NHS Foundation Trust
        • Contact:
        • Principal Investigator:
          • Neil Srinivasan
      • Birmingham, United Kingdom
        • Recruiting
        • Queen Elizabeth Hospital
        • Contact:
        • Principal Investigator:
          • Manish Kalla
      • Blackpool, United Kingdom
        • Recruiting
        • Blackpool Victoria Hospital
        • Contact:
        • Principal Investigator:
          • Alison Seed
      • Bournemouth, United Kingdom
        • Recruiting
        • University Hospitals Dorset NHS Foundation Trust
        • Contact:
        • Principal Investigator:
          • Richard Balasubramaniam
      • Cambridge, United Kingdom, CB2 0AY
        • Recruiting
        • Royal Papworth Hospital NHS Foundation Trust
        • Principal Investigator:
          • Claire Martin
        • Contact:
      • Coventry, United Kingdom
        • Recruiting
        • University Hospitals Coventry and Warwickshire NHS Trust
        • Contact:
        • Principal Investigator:
          • Tarv Dhanjal
      • Glasgow, United Kingdom, G81 4DY
        • Recruiting
        • Golden Jubilee National Hospital
        • Principal Investigator:
          • Roy Gardner
        • Contact:
      • Hull, United Kingdom
        • Recruiting
        • Hull University Teaching Hospitals NHS Trust
        • Principal Investigator:
          • Andrew Clark
        • Contact:
      • Leeds, United Kingdom
        • Recruiting
        • Leeds Teaching Hospitals NHS Trust
        • Contact:
        • Principal Investigator:
          • Muzahir Tayebjee
      • Leicester, United Kingdom
        • Recruiting
        • Glenfield Hospital
        • Contact:
        • Principal Investigator:
          • Louise Clayton
      • Liverpool, United Kingdom
        • Recruiting
        • Liverpool Heart and Chest Hospital NHS Foundation Trust
        • Principal Investigator:
          • Rajiv Sankaranarayanan
      • London, United Kingdom
        • Recruiting
        • Imperial College Healthcare NHS Trust
        • Contact:
        • Principal Investigator:
          • Prapa Kanagaratnam
      • London, United Kingdom
        • Recruiting
        • Barts Health NHS Trust
        • Contact:
        • Principal Investigator:
          • Shohreh Honarbakhsh
      • London, United Kingdom
        • Recruiting
        • St George's University Hospitals NHS Foundation Trust
        • Contact:
        • Principal Investigator:
          • Mark Gallagher
      • London, United Kingdom
        • Recruiting
        • St Thomas' Hospital
        • Principal Investigator:
          • Aldo Rinaldi
        • Contact:
      • London, United Kingdom, UB9 6JH
        • Recruiting
        • Royal Brompton and Harefields Hospitals
        • Principal Investigator:
          • Shouvik Haldar
        • Contact:
      • Middlesbrough, United Kingdom
        • Recruiting
        • James Cook University Hosptial
        • Contact:
        • Principal Investigator:
          • Andrew Thornley
      • Newcastle, United Kingdom
        • Recruiting
        • Freeman Hospital, Royal Victoria Infirmary
        • Principal Investigator:
          • Moloy Das
        • Contact:
      • Nottingham, United Kingdom
        • Recruiting
        • Nottingham University Hospital NHS Trust
        • Contact:
        • Principal Investigator:
          • Shahnaz Jamil-Copley
      • Plymouth, United Kingdom
        • Recruiting
        • University Hospitals Plymouth NHS Trust
        • Contact:
        • Principal Investigator:
          • Sharon Man
      • Portsmouth, United Kingdom
        • Recruiting
        • Queen Alexandra Hospital
        • Contact:
        • Principal Investigator:
          • Senthil Kirubakaran
      • Southampton, United Kingdom
      • Swansea, United Kingdom
        • Recruiting
        • Swansea Bay University Health Board
        • Contact:
        • Principal Investigator:
          • Dewi M Thomas

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion criteria:

  1. Patients aged ≥18 years.
  2. Patient is willing and able to give informed consent for participation.
  3. Able and willing to comply with all study requirements, including ability to participate in study for 12 months.
  4. Willing to allow their General Practitioner (GP) to be notified of participation in the study.

  5. 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)
  6. 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.
  7. New York Heart Association Classification (NYHA) class II to III

  8. 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.

    1. 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.
    2. For those with LVEF 41-49% and with ongoing atrial fibrillation/flutter, NTproBNP of ≥600pg/mL is required within 12 months prior randomisation.
    3. For those with LVEF ≤40%, NTproBNP is not required

Exclusion criteria:

  1. Long standing (>3 year) persistent or permanent AF.
  2. Previous atrioventricular (AV) nodal ablation.
  3. Previous pulmonary vein isolation (PVI) or surgical ablation.
  4. Recent (<90 days) (type 1 spontaneous) myocardial infarction (type 2 myocardial infarctions are not an exclusion criterion), percutaneous coronary intervention, coronary artery bypass grafting, cardiac resynchronisation therapy or stroke.
  5. Severe aortic or pulmonary valve disease.
  6. Severe primary or secondary mitral valve regurgitation.
  7. Active illness (other than HF) likely to result in death within 2 years.
  8. People who are pregnant or planning to become pregnant during the trial.
  9. People who are breastfeeding.
  10. Known allergy to contrast.
  11. Contraindication for PVI.
  12. Other conditions that may prevent subjects from adhering to the trial protocol, in the opinion of the investigator.
  13. Currently participating in another randomised controlled trial of another drug or medical device.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: The optimal medical therapy as per standard of care
Participants randomised to the optimal medical therapy arm will receive optimal medical therapy according to the most contemporary ESC HF guidelines.
Other: The catheter ablation
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
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to first all-cause death and urgent CV hospitalisation
Time Frame: 2 years minimum (range: 2-5.5 years)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total (first and recurrent) all-cause death and urgent cardiovascular hospitalisations.
Time Frame: 2 years minimum (range: 2-5.5 years)
Total (first and recurrent) number of all-cause deaths and urgent cardiovascular-related hospitalisations. Joint frailty models will be used to analyse time to death and recurrent urgent CV hospitalisations simultaneously. Additionally, negative binomial regression will be used to analyse the number of recurrent urgent CV hospitalisations.
2 years minimum (range: 2-5.5 years)
Time to all-cause death
Time Frame: 2 years minimum (range: 2-5.5 years)
Time to all-cause death will be analysed using Cox proportional hazards regression model for time to event, matching the primary outcome.
2 years minimum (range: 2-5.5 years)
Total (first and recurrent) all-cause death and urgent HF hospitalisations
Time Frame: 2 years minimum (range: 2-5.5 years)
Total (first and recurrent) number of all-cause deaths and urgent heart failure-related hospitalisations. Joint frailty models will be used to analyse time to death and recurrent urgent HF hospitalisations simultaneously. Additionally, negative binomial regression will be used to analyse the number of recurrent urgent HF hospitalisations.
2 years minimum (range: 2-5.5 years)
Cardiovascular death
Time Frame: 2 years minimum (range: 2-5.5 years)
Total number of cardiovascular-related deaths. Cox proportional hazards regression model for time to event, matching the primary outcome.
2 years minimum (range: 2-5.5 years)
QoL at 6 and 12 months assessed using the KCCQ-CSS.
Time Frame: 12 months
Quality of Life (QoL) at 6 and 12 months assessed using the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS). Linear mixed effects regression models will be used to analyse repeated measurements of QoL. Scored from 0- 100, with a higher score indicating better health.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University College, London

Investigators

  • Principal Investigator: Pier Lambiase, University College, London
  • Principal Investigator: Mark Petrie, University of Glasgow

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 21, 2024

Primary Completion (Estimated)

December 15, 2031

Study Completion (Estimated)

December 15, 2031

Study Registration Dates

First Submitted

July 1, 2024

First Submitted That Met QC Criteria

July 10, 2024

First Posted (Actual)

July 17, 2024

Study Record Updates

Last Update Posted (Actual)

May 4, 2026

Last Update Submitted That Met QC Criteria

April 28, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 136905
  • 281142 (Registry Identifier: IRAS project ID)
  • 24/LO/0301 (Other Identifier: London - Hampstead Research Ethics Committee)
  • CS/F/21/190034 CRAAFT-HF (Other Grant/Funding Number: British Heart Foundation)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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