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Trial registered on ANZCTR


Registration number
ACTRN12618000292279
Ethics application status
Approved
Date submitted
12/01/2018
Date registered
26/02/2018
Date last updated
20/02/2019
Date data sharing statement initially provided
20/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised controlled study of atrial fibrillation ablation vs medical therapy in patients with persistent atrial fibrillation and heart failure with preserved ejection fraction: RCT STALL-HFpEF
Scientific title
RCT STALL-HFpEF: Randomised controlled study of Atrial Fibrillation and Left Ventricular Remodelling in Heart Failure with Preserved Ejection Fraction. Impact on pulmonary capillary wedge pressure.
Secondary ID [1] 293805 0
Nil known
Universal Trial Number (UTN)
U1111-1188-4814
Trial acronym
RCT STALL-HFpEF
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atrial Fibrillation 300526 0
Heart Failure 300527 0
Condition category
Condition code
Cardiovascular 300390 300390 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a multi centre randomized controlled trial examining a strategy of rhythm control using AF ablation versus medical rate control and optimal medical therapy in patients with co-morbid persistent AF and heart failure with preserved ejection fraction (AF-HFPEF)

Procedures: Standard / Routine pulmonary vein isolation will be performed in patients undergoing ablation. The standard procedure involves minimally invasive procedure in which patient is taken to the cardiac catheter laboratory. Procedure performed under general anaesthesia. femoral venous access obtained through with catheters are advanced into the heart. The pulmonary veins in the left atrium are targeted with radio frequency ablation using special catheters that can deliver radiofrequency energy to the atrial tissue. At the end of the procedure, all sheaths and catheters removed from body.

Care provided by Cardiologist and Electrophysiologists with minimum 5 years procedural experience who will be looking after the patients regardless of whether they are part of the trial.

a) what the Intervention involves: Atrial fibrillation / pulmonary vein isolation (PVI) ablation. Compares invasive ablative management of atrial fibrillation vs optimal medical therapy. Involve comparing surgical intervention vs medical therapy alone. PVI is commonly performed for patients with atrial fibrillation.
b) Frequency / duration of intervention: Atrial fibrillation ablation is performed once initially if necessary repeat procedure offered if there is a recurrence as part of standard care. Follow up in clinic once every three months for a 20 minute consultation for 6 months as per usual care.
c) Mode of administration: In person. During surgery or face to face interaction during follow up.
d) Procedure is performed by experienced operators at participating sites who perform these procedures as part of their usual practice with at least 5 years experience.
e) Procedure and follow up will be performed at participating sites as per usual practice.
f) Target intensity – Not applicable
g) Adherence – Not applicable
h) Follow up period: 6 months
i) Titration: There is no titration in patients undergoing AF ablation. Strategy of ablation will be fixed in all patients undergoing AF ablation. The ablation may be individualised based on intraoperative findings such as need for additional ablation.
Intervention code [1] 296092 0
Treatment: Surgery
Comparator / control treatment
Optimal medical therapy: Introduction and maintenenace of rate control medications. No new anti arrhythmic therapy will be initiated as these patients are meant to have tried and failed rhythm control attempts. Initiation and maintenance of maximal tolerated spironolactone dose.

Rate control mediucations such as non selective betablockers or non dihydropyridine alcium channel blockers such as Verapamil or Diltiazem. Dose for these medications will be maximum tolerated dose as recommended.

REcommendation will be based on the latest 2017 ACC/AHA/HFSA Focused Update Guideline for the Management of Heart Failure
Control group
Active

Outcomes
Primary outcome [1] 304422 0
Primary outcome of change in peak exercise pulmonary capillary wedge pressure from baseline to 6 months:
The peak exercise PCWP will me measured using a standardised exercise protocol using a bike pedal in the supine position. PCWP will be measured using a ballon tipped Swan-Ganz catheter inseretd via the cubital vein.
Timepoint [1] 304422 0
6 months
Secondary outcome [1] 341894 0
NYHA status
Timepoint [1] 341894 0
6 months
Secondary outcome [2] 341895 0
Diffuse ventricular fibrosis on CMR T1 mapping (LV T1 time)
Timepoint [2] 341895 0
6 months
Secondary outcome [3] 341896 0
Difference in mortality. This will be assessed through planned regular patient follow up and through hospital records.
Timepoint [3] 341896 0
6 Months
Secondary outcome [4] 341897 0
Proportion of patients with an improvement in AF burden by >90% after one or two ablations. This will be assesed by either loop recorders, patient transmitted rhythm stripes using Alive Cor or through series of Holter monitor recording at follow up
Timepoint [4] 341897 0
At 6 months
Secondary outcome [5] 341898 0
Freedom from documented any atrial arrhythmia episodes stratified by degree of HFpEF based on peak PCWP and peak VO2. The arrhythmia will be assesed by either loop recorders, patient transmitted rhythm stripes using Alive Cor or through series of Holter monitor recording at follow up
Timepoint [5] 341898 0
6 months
Secondary outcome [6] 341900 0
Peak VO2 change in medical group vs ablation group. This will be measured using a standardised protocol currently used at Baker institute using cycle ergometer.
Timepoint [6] 341900 0
6 months
Secondary outcome [7] 343042 0
Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) questionnaire score
Timepoint [7] 343042 0
6 months
Secondary outcome [8] 343043 0
MLHF questionnaires scores
Timepoint [8] 343043 0
6 months
Secondary outcome [9] 343044 0
Difference in Hospitalisation. This will be assessed through planned regular patient follow up and through hospital records.
Timepoint [9] 343044 0
6 Months

Eligibility
Key inclusion criteria
1. Patients with documented HFpEF based on the 2016 ESC guidelines.
2. Patients aged greater than 18 years old
3. Patients undergoing a first-time ablation procedure for persistent AF (Persistent AF will be defined as a sustained episode lasting >7 days and less than three years)
4. Patients with symptomatic AF that is refractory to at least one antiarrhythmic (if clinically appropriate) medication and trial of cardioversion
5. At least one episode of persistent AF must have been documented by ECG, holter, loop recorder, telemetry, trans telephonic monitoring (TTM), or implantable device within last 2 months of enrolment in this investigation
6. Patients must be able and willing to provide written informed consent to participate in this investigation; and
7. Patients must be willing and able to comply with all peri-ablation and follow- up requirements
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Paroxysmal AF (defined as a sustained episode lasting < 7 days)
2. Patients with long-standing persistent AF (AF > or equal to 3 years)
3. Patients for whom cardioversion or sinus rhythm will never be attempted/pursued
4. Patients with AF felt to be secondary to an obvious reversible cause
5. Patients with contraindications to systemic anticoagulation with heparin or coumadin or a direct thrombin inhibitor
6. Patients with left atrial size > or = 60 mm (2D echocardiography, parasternal long axis view); and
7. Pregnancy
8. Ejection fraction of <50% on echocardiogram.
9. End stage renal, eGFR <45 or hepatic failure.
10. Severe coronary artery disease
11. Severe pulmonary disease
12. Severe valvular heart disease or cyanotic congenital heart disease.
13. Diagnosis of hypertrophic cardiomyopathy.
14. Unable to consent
15. Unable to undergo MRI
16. Unable to undertake exercise testing RHC or VO2 testing.
17. Pacemaker or defibrillator implant
18. Untreated OSA
19. BMI >40
20. Uncontrolled AF despite maximal medical therapy (HR >100 at rest)
21. Recovered cardiomyopathy
22. Uncontrolled hypertension (SBP >160mmHg)

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)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation - Computer generated sequence
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
We are planning a study of a continuous response variable from independent control and experimental subjects with 1 medical treatment subject per ablation subject. In a previous study the pulmonary capillary wedge pressure (PCWP) within each subject group was normally distributed with standard deviation 6.3mmHg. If the true difference in the ablation and medical subjects means is 5mmHg, we will need to study 25 ablation subjects and 25 medical subjects to be able to reject the null hypothesis that the population means of the ablation and medical groups are equal with probability (power) 0.8. The Type I error probability associated with this test of this null hypothesis is 0.05. With a expected 10% drop out rate we will need a total of 56 patients (28 in each arm) .

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 9734 0
The Alfred - Prahran
Recruitment hospital [2] 9735 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment postcode(s) [1] 18512 0
3004 - Melbourne
Recruitment postcode(s) [2] 18513 0
3004 - Prahran
Recruitment postcode(s) [3] 18514 0
3050 - Parkville

Funding & Sponsors
Funding source category [1] 298380 0
Hospital
Name [1] 298380 0
Alfred Health
Address [1] 298380 0
55 Commercial Rd, Melbourne VIC 3004
Country [1] 298380 0
Australia
Primary sponsor type
Hospital
Name
Alfred Health
Address
55 Commercial Rd, Melbourne VIC 3004
Country
Australia
Secondary sponsor category [1] 297505 0
None
Name [1] 297505 0
Address [1] 297505 0
Country [1] 297505 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299372 0
Alfred HREC
Ethics committee address [1] 299372 0
55 Commercial road, Melbourne, Victroia, 3004
Ethics committee country [1] 299372 0
Australia
Date submitted for ethics approval [1] 299372 0
21/09/2017
Approval date [1] 299372 0
02/10/2017
Ethics approval number [1] 299372 0
HREC/17/Alfred/128 (Local Reference: Project 425/17)

Summary
Brief summary
The aim of this project is to determine if ablation procedure will offer benefit over optimal medical management in people with persistant AF & HFpEF. We will also determine what changes are seen in the heart with AF and how it affects the heart’s structure & exercise capacity (Exercise RHC and VO2 peak). We will determine if these changes can improve with ablation.
Trial website
Trial related presentations / publications
Public notes
Supervised by and In collaboration with Prof. Jonathan KALMAN, Melbourne Heart Centre, Royal Melbourne Hosp. Royal Pde, Parkville VIC 3052

Contacts
Principal investigator
Name 69534 0
Dr Liang Han Ling
Address 69534 0
Dr. Liang Han Ling, Alfred Health, Heart Centre Level 3, 55 Commercial Road, Melbourne, Victoria 3004
Country 69534 0
Australia
Phone 69534 0
+61390762000
Fax 69534 0
Email 69534 0
hsugumar@yahoo.com
Contact person for public queries
Name 69535 0
Dr Hariharan Sugumar
Address 69535 0
Alfred Health, 55 Commercial Road, Melbourne, Vic 3004
Country 69535 0
Australia
Phone 69535 0
+61390762000
Fax 69535 0
Email 69535 0
hsugumar@yahoo.com
Contact person for scientific queries
Name 69536 0
Dr Hariharan Sugumar
Address 69536 0
Alfred Health, 55 Commercial Road, Melbourne, Victoria, 3004
Country 69536 0
Australia
Phone 69536 0
+61390762000
Fax 69536 0
Email 69536 0
hsugumar@yahoo.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data collected will be de identified
What supporting documents are/will be available?
No other documents available
Summary results
No Results