Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000502932
Ethics application status
Approved
Date submitted
29/03/2020
Date registered
22/04/2020
Date last updated
11/08/2024
Date data sharing statement initially provided
22/04/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
CAMERA-MRI II trial: Catheter Ablation versus Medical Rate Control of Atrial Fibrillation with Systolic Heart Failure and Myocardial Fibrosis – an MRI Guided Multi-Centre Randomised Controlled Clinical Trial
Scientific title
CAMERA-MRI II trial: Catheter Ablation versus Medical Rate Control of Atrial Fibrillation with Systolic Heart Failure and Myocardial Fibrosis – an MRI Guided Multi-Centre Randomised Controlled Clinical Trial
Secondary ID [1] 300881 0
Nil known
Universal Trial Number (UTN)
Trial acronym
CAMERA-MRI II
Linked study record

Health condition
Health condition(s) or problem(s) studied:
atrial fibrillation 316813 0
heart failure 316814 0
Condition category
Condition code
Cardiovascular 315021 315021 0 0
Other cardiovascular diseases
Surgery 315022 315022 0 0
Surgical techniques

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Interventional

1. Name: CAMERA-MRI II trial: Catheter Ablation versus Medical Rate Control of Atrial Fibrillation with Systolic Heart Failure and Myocardial Fibrosis – an MRI Guided Multi-Centre Randomised Controlled Clinical Trial.

2. Goal/Elements: Atrial fibrillation (AF) and heart failure (HF) are both emerging
epidemics in developing countries with a significant influence upon morbidity and mortality. HF affects 1.5-2% of the Australian population as extrapolated by worldwide data, almost half of whom have ischaemic cardiomyopathy. AF and HF share common pathophysiological mechanisms, whereby AF may precipitate, worsen or be a consequence of HF. The restoration of sinus rhythm has the potential to improve LV function and clinical outcomes in patients with HF and concurrent AF. Catheter ablation (CA) has established itself as superior to medical therapy, particularly in patients with HF, with an acceptable risk profile, albeit with a lower procedural efficacy compared to patients without HF. Although, early clinical trials have demonstrated LVEF improved irrespective of HF aetiology, other studies suggest pre-existing structural heart disease, such as prior myocardial infarction predicts reduced procedural efficacy and poor recovery of left ventricular (LV) systolic function. The CAMERA-MRI trial specifically focused on patients with AF and idiopathic or otherwise unexplained cardiomyopathy and showed that MRI-detected myocardial fibrosis could predict the extent of ventricular recovery following CA.

The recent CASTLE-AF study reported improved mortality and unplanned HF hospitalisation following CA in all aetiologies of HF with concurrent AF, including ischaemic cardiomyopathy, however the impact of myocardial fibrosis or heart failure aetiology was not specifically evaluated. This randomised clinical trial will evaluate the role of cardiac MRI (CMR) in all patients with AF and heart failure, including those with ischaemic cardiomyopathy or known contributing myocardial fibrosis on LV recovery and clinical outcomes at 12 months.

3. Materials: This trial incorporates standard practice for patients with AF and HF. All patients being considered for this trial will be invited to meet the study investigators to assess study eligibility and they will be provided with written information regarding AF and HF management options available as per standard routine care. If they meet eligibility based on the study criteria, they will then be offered enrolment in our trial. If they choose to, addition written information will be provided at that point about the intervention (catheter ablation). All trial patients will be followed up closely at 3, 6 and 12 months after the intervention. Participants randomised to the medical rate control group will be followed up at the same time intervals.

4. Catheter Ablation Procedure: Standard pulmonary vein isolation will be performed in all patients randomised to the CA group by an Electrophysiologist. Additional ablation may be performed at the operator's discretion. This is a minimally invasive procedure performed under general anaesthesia in the cardiac catheter laboratory. The procedure is performed via femoral venous access (ultrasound guidance) with catheters advanced into the heart. The pulmonary veins in the left atrium are targeted with either radio frequency ablation (RFA) or cryoablation using special catheters that can deliver energy to the atrial tissue. At the end of the procedure, all sheaths and catheters are removed from body.

5. Standard care will be provided by the treating cardiologist or electrophysiologists, regardless of whether the patient chooses to participate in the trial.

6. Mode of Delivery: Patient care, treatments and follow up will be provided directly through the participating institutions.

7. Location/s: The participating sites include recruitment and procedural sites: the Alfred Hospital, the Royal Melbourne Hospital, University Hospital Geelong, Monash Medical Centre, Westmead Hospital, Mulgrave Private Hospital, the Epworth Hospital and Cabrini Hospital. Sunshine Hospital will be a recruitment site. Patients can be referred from non-participating institutions to any of the participating recruitment sites.

8. Intervention: Catheter ablation will be performed once as part of the trial. Subsequent ablation may be considered based on the patient's individual clinical circumstances, clinical indication and treating specialist recommendation. The procedure duration is approximately 2 hours.

9. Tailoring: The ablation strategy will be at the operator's discretion. Continuation of anti-arrhythmic medications beyond the ablation procedure will be at the operator's discretion based on the patient's clinical circumstance.

10. Modification: Any intervention or modification to the intended intervention that is deemed necessary for the benefit of the patient will be undertaken as needed.
Intervention code [1] 317207 0
Treatment: Surgery
Comparator / control treatment
The control arm will be standard medical rate control based on the 2016 ESC guidelines for AF management(1).

Reference:
(1) Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC guidelines for the management of atrial
fibrillation developed in collaboration with EACTS. Eur Heart J 2016;37:2893–962.
Control group
Active

Outcomes
Primary outcome [1] 323322 0
Change in LV ejection fraction (EF) on echocardiography and cardiac MRI from baseline to 12 months in LGE-positive catheter ablation versus medical rate control group
Timepoint [1] 323322 0
1. LVEF at 12 months
2. Change in LVEF from baseline to 12 months in catheter ablation versus medical rate control groups
Primary outcome [2] 323324 0
Comparison of change in LV systolic function on echocardiography and cardiac MRI from baseline to 12 months in LGE-positive catheter ablation versus LGE-negative catheter ablation group
Timepoint [2] 323324 0
LV systolic function at 12 months.
Secondary outcome [1] 381552 0
Composite secondary endpoint of the impact of catheter ablation on clinical outcomes (composite of mortality and HF hospitalisation) in AF and HF compared to medical rate control at 12 months, assessed through electronic medical records.
Timepoint [1] 381552 0
This will be assessed at 12 months assessed through electronic medical records and clinic follow up.
Secondary outcome [2] 381560 0
Impact of myocardial fibrosis burden on LV recovery in CA vs MRC at 12 months.
Timepoint [2] 381560 0
Myocardial fibrosis and LV recovery at 12 months on echocardiography and cardiac MRI.
Secondary outcome [3] 381561 0
Impact of diffuse fibrosis (native and post contrast T1 mapping) on ventricular recovery at 12 months.
Timepoint [3] 381561 0
This will be assessed at 12 months on cardiac MRI.
Secondary outcome [4] 381562 0
Impact of catheter ablation on all-cause mortality.
Timepoint [4] 381562 0
This will be assessed through electronic medical records and clinic follow up at 3, 6 and 12 months post ablation.
Secondary outcome [5] 381563 0
Change in functional status between catheter ablation and medical rate control groups measured via 6-minute walk test.
Timepoint [5] 381563 0
This will be assessed at 6 and 12 months at clinic follow up.
Secondary outcome [6] 381564 0
Change in left atrial dimensions following catheter ablation on transthoracic echocardiography and cardiac MRI.
Timepoint [6] 381564 0
This will be assessed during follow up at 12 months.
Secondary outcome [7] 381565 0
Complication rates at 12 months (including pulmonary vein stenosis, perforation, tamponade, stroke) Complications will be documented immediately at the time of procedure and during the follow up visits at 3, 6 and 12 months through electronic medical records and participant-reported events.
Timepoint [7] 381565 0
Procedural complications will be assessed in the peri-procedural period and during follow up at 3,6 and 12 months.
Secondary outcome [8] 381566 0
Recurrence of AF for >30 seconds, assessed Holter monitor, AliveCor monitor or ECG.
Timepoint [8] 381566 0
AF recurrence will be assessed at 6 and 12 months post procedure.
Secondary outcome [9] 381567 0
AF burden, assessed via Holter monitor (medical rate control group) or AliveCor (catheter ablation group) as proportion of recordings in AF.
Timepoint [9] 381567 0
This will be assessed prior to the ablation procedure and at 12 months follow up.
Secondary outcome [10] 381568 0
Requirement for anti-arrhythmic medication beyond 3 months post ablation. This will be documented during the clinic follow up visits at 3, 6 and 12 months,
Timepoint [10] 381568 0
This will be assessed at 3, 6 and 12 months post ablation.
Secondary outcome [11] 381866 0
Impact of catheter ablation on unplanned HF hospitalisations.
Timepoint [11] 381866 0
This will be assessed through electronic medical records and clinic follow up at 3, 6 and 12 months post ablation.
Secondary outcome [12] 381867 0
Impact of catheter ablation on cardiovascular mortality.
Timepoint [12] 381867 0
This will be assessed through electronic medical records and clinic follow up at 3, 6 and 12 months post ablation.
Secondary outcome [13] 381868 0
Impact of catheter ablation on functional testing (measured via cardiopulmonary exercise testing: VO2 max) at 6 and 12 month clinic follow up.
Timepoint [13] 381868 0
Measured at 6 and 12 months follow up.
Secondary outcome [14] 381869 0
Impact of catheter ablation on NYHA class at 3, 6 and 12 months through clinic follow up.
Timepoint [14] 381869 0
Assessed at 3, 6 and 12 months follow up.
Secondary outcome [15] 381870 0
Impact of catheter ablation on cardiac biomarkers (serum BNP) at 6 and 12 months through electronic medical record and clinic follow up.
Timepoint [15] 381870 0
Assessed at 6 and 12 month follow up.
Secondary outcome [16] 381871 0
Assess impact of catheter ablation on patient reported outcome measures (Minnesota Living with Heart Failure Questionnaire) at 3, 6 and 12 months.
Timepoint [16] 381871 0
Assessed at 3, 6 and 12 month follow up.
Secondary outcome [17] 381872 0
Change in left ventricular dimensions following catheter ablation on transthoracic echocardiography and cardiac MRI.
Timepoint [17] 381872 0
Assessed at 12 months follow up.

Eligibility
Key inclusion criteria
Patients aged 18 years or older with AF and HF (LVEF 45% or below on CMR) who have trialled and failed at least 1 anti-arrhythmic agent or experienced AF recurrence following electrical cardioversion (DCR)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
-CMR contraindication (eGFR <35mL/min, MRI-incompatible device)
-Catheter ablation contraindications such as ASD closure, LAA thrombus, anticoagulation contraindication
-AF >5yrs (where sinus rhythm is unlikely to be achieved or maintained)
-LVEF > 45% (CMR)
-Valvular AF
-Specific reversible HF aetiology (uncontrolled thyroid disease, excessive alcohol, myocarditis)
Within 3 months of planned cardiac intervention (PCI/CABG/implantable cardiac device) or planned intervention within 12 months of study enrolment.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Centralised computer randomisation
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation. Randomisation will occur in a box fashion on a centre basis to ensure even treatment allocation across study sites.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Data will be analysed using SPSSv.26. All analyses will be conducted on an intention to treat basis using standard statistical methods for categorical and continuous data. The prior CAMERA-MRI study from our group demonstrated a mean improvement in LVEF of 11.6 ± 10.3 in the LGE-positive CA group, compared to 4.8 ± 8.5 in the MRC group at 6 months. We estimated a total sample size of 74 patients would be needed in order to reach a statistical power of 80% with the probability of type one error being 0.05. This was calculated using a standard deviation of 10.3 based on the CAMERA-MRI study10. The calculated sample size reflects the sample required to detect an improvement at 6 months based on the previous CAMERA-MRI trial. It is likely this benefit would be amplified at 12-months and therefore we feel the estimated sample size of 74 patients overall (37 per group) is sufficient to statistically power for the primary endpoint. We accounted for a 10% drop out rate, increasing the total sample size to 80 participants (40 per LGE-positive treatment group).

Recruitment will continue until 80 LGE-positive patients have been randomised. Differences in proportions and categorical variables will be compared using chi-squared analysis or Fisher's exact test. Continuous variables will be analysed using Student's t-test. Confidence intervals for the difference of two independent proportions will be calculated using the Newcombe-Wilson score method (uncorrected). McNemar's test will compare proportions of paired samples.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
14/08/2020
Actual
29/09/2020
Date of last participant enrolment
Anticipated
29/09/2023
Actual
8/06/2023
Date of last data collection
Anticipated
30/09/2024
Actual
28/06/2024
Sample size
Target
120
Accrual to date
Final
120
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 16163 0
The Alfred - Melbourne
Recruitment hospital [2] 16164 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [3] 16165 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [4] 16166 0
Melbourne Private Hospital - Parkville
Recruitment hospital [5] 16167 0
Cabrini Hospital - Malvern - Malvern
Recruitment hospital [6] 16168 0
Sunshine Hospital - St Albans
Recruitment hospital [7] 16169 0
The Valley Private Hospital - Mulgrave
Recruitment hospital [8] 16170 0
Epworth Richmond - Richmond
Recruitment hospital [9] 20953 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment postcode(s) [1] 29704 0
3004 - Melbourne
Recruitment postcode(s) [2] 29705 0
3050 - Parkville
Recruitment postcode(s) [3] 29706 0
3168 - Clayton
Recruitment postcode(s) [4] 29707 0
3052 - Parkville
Recruitment postcode(s) [5] 29708 0
3144 - Malvern
Recruitment postcode(s) [6] 29709 0
3021 - St Albans
Recruitment postcode(s) [7] 29710 0
3170 - Mulgrave
Recruitment postcode(s) [8] 29711 0
3121 - Richmond
Recruitment postcode(s) [9] 35770 0
3220 - Geelong
Recruitment outside Australia
Country [1] 22457 0
United Kingdom
State/province [1] 22457 0
St Bartholomew's Hospital, London, England
Country [2] 26492 0
United Kingdom
State/province [2] 26492 0
Queen Elizabeth Hospital Birmingham

Funding & Sponsors
Funding source category [1] 305329 0
Hospital
Name [1] 305329 0
Alfred Hospital
Country [1] 305329 0
Australia
Funding source category [2] 305332 0
Government body
Name [2] 305332 0
NHMRC
Country [2] 305332 0
Australia
Funding source category [3] 305333 0
Other Collaborative groups
Name [3] 305333 0
Baker Heart and Diabetes Institute
Country [3] 305333 0
Australia
Primary sponsor type
Hospital
Name
Alfred Hospital
Address
55 Commercial Rd, Melbourne VIC 3004, Australia
Country
Australia
Secondary sponsor category [1] 305701 0
None
Name [1] 305701 0
Address [1] 305701 0
Country [1] 305701 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305667 0
Alfred Health Ethics Committee
Ethics committee address [1] 305667 0
Ethics committee country [1] 305667 0
Australia
Date submitted for ethics approval [1] 305667 0
23/03/2020
Approval date [1] 305667 0
01/06/2020
Ethics approval number [1] 305667 0
HREC/58208/Alfred-2020

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 101154 0
Dr Sandeep Prabhu
Address 101154 0
Department of Cardiology
Alfred Health
55 Commercial Rd, Melbourne VIC 3004
Country 101154 0
Australia
Phone 101154 0
+613 9076 2000
Fax 101154 0
+613 9076 2461
Email 101154 0
[email protected]
Contact person for public queries
Name 101155 0
Louise Segan
Address 101155 0
Department of Cardiology
Alfred Health
55 Commercial Rd, Melbourne VIC 3004
Country 101155 0
Australia
Phone 101155 0
+613 9076 2000
Fax 101155 0
+613 9076 2461
Email 101155 0
[email protected]
Contact person for scientific queries
Name 101156 0
Louise Segan
Address 101156 0
Department of Cardiology
Alfred Health
55 Commercial Rd, Melbourne VIC 3004
Country 101156 0
Australia
Phone 101156 0
+613 9076 2000
Fax 101156 0
+613 9076 2461
Email 101156 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
7460Study protocol    379524-(Uploaded-08-08-2024-12-54-55)-CAMERA MRI II Study Protocol_FINAL.pdf



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.