Clinical Trial Results:
Pulmonary vein isolation with versus without continued antiarrhythmic drug treatment in subjects with persistent atrial fibrillation: a prospective multi-centre randomized controlled clinical study (POWDER-AF2 study)
|
Summary
|
|
EudraCT number |
2018-002103-33 |
Trial protocol |
AT DK ES FR |
Global end of trial date |
01 Aug 2023
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
17 Dec 2023
|
First version publication date |
17 Dec 2023
|
Other versions |
|
Summary report(s) |
Published Study Paper |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
1080719
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
ClinicalTrials.gov: NCT03437356 | ||
|
Sponsors
|
|||
Sponsor organisation name |
AZ Sint-Jan Brugge-Oostende AV
|
||
Sponsor organisation address |
Ruddershove 10, Bruges, Belgium,
|
||
Public contact |
Anthony Demolder, Anthony Demolder, anthony.demolder@ugent.be
|
||
Scientific contact |
Anthony Demolder, Anthony Demolder, anthony.demolder@ugent.be
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
01 Aug 2023
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
01 Aug 2023
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
01 Aug 2023
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
We aimed to study whether continued ADT (antiarrhythmic drug treatment) (ADT ON) beyond the 3 month blanking period reduces recurrrence of atrial tachyarrhyhtmia (ATA) in the first year after contact-force guided pulmonary vein isolation (PVI) for persistent AF.
|
||
Protection of trial subjects |
As per standard follow-up.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
30 Jun 2018
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Spain: 17
|
||
Country: Number of subjects enrolled |
Austria: 36
|
||
Country: Number of subjects enrolled |
Denmark: 11
|
||
Country: Number of subjects enrolled |
Belgium: 117
|
||
Country: Number of subjects enrolled |
Switzerland: 19
|
||
Worldwide total number of subjects |
200
|
||
EEA total number of subjects |
181
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
20
|
||
From 65 to 84 years |
180
|
||
85 years and over |
0
|
||
|
||||||||||||||||
|
Recruitment
|
||||||||||||||||
Recruitment details |
- | |||||||||||||||
|
Pre-assignment
|
||||||||||||||||
Screening details |
Patients planned for first-time ablation of PersAF (defined as any prior episode ≥7 days)8 were locally screened for inclusion. Inclusion criteria were symptomatic PersAF resistant to ongoing or prior ADT (failed class IC or III ADT) and at least 1 episode of PersAF in the last year. | |||||||||||||||
|
Period 1
|
||||||||||||||||
Period 1 title |
Study period (overall period)
|
|||||||||||||||
Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
|
|||||||||||||||
Blinding used |
Not blinded | |||||||||||||||
Blinding implementation details |
At the time of procedural planning, enrolled patients were randomly assigned (block randomization with center stratification) to continue (ADT ON group) or discontinue previously ineffective ADT (ADT OFF group) after the 3-month blanking period up to 1 year after ablation. In the ADT ON group, ADT was continued after verifying for correct dosage according to the European Society of Cardiology guidelines on the treatment of AF.
|
|||||||||||||||
|
Arms
|
||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||
|
Arm title
|
ADT ON | |||||||||||||||
Arm description |
In the ADT ON group, ADT was continued after verifying for correct dosage according to the European Society of Cardiology guidelines on the treatment of AF. If not already the case, β-blocking agents were added to Class 1C ADT. In the case of preprocedural use of amiodarone, ADT was switched to conventional class 1C or sotalol. In the ADT OFF group, all antiarrhythmic medications were discontinued after the 3-month blanking period with the exception of β-blocking agents if these were given for other indications (eg, hypertension, ischemic heart disease). | |||||||||||||||
Arm type |
Active comparator | |||||||||||||||
Investigational medicinal product name |
Class 1C antiarrhythmic drugs
|
|||||||||||||||
Investigational medicinal product code |
||||||||||||||||
Other name |
||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||
Dosage and administration details |
According to the Summary of Product Characteristics (SmPC) and in line with physician instructions.
|
|||||||||||||||
|
Arm title
|
ADT OFF | |||||||||||||||
Arm description |
At the time of procedural planning, enrolled patients were randomly assigned (block randomization with center stratification) to continue (ADT ON group) or discontinue previously ineffective ADT (ADT OFF group) after the 3-month blanking period up to 1 year after ablation. In the ADT OFF group, all antiarrhythmic medications were discontinued after the 3-month blanking period with the exception of β-blocking agents if these were given for other indications (eg, hypertension, ischemic heart disease). | |||||||||||||||
Arm type |
No intervention | |||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
|
|||||||||||||||
|
||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
ADT ON
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
In the ADT ON group, ADT was continued after verifying for correct dosage according to the European Society of Cardiology guidelines on the treatment of AF. If not already the case, β-blocking agents were added to Class 1C ADT. In the case of preprocedural use of amiodarone, ADT was switched to conventional class 1C or sotalol. In the ADT OFF group, all antiarrhythmic medications were discontinued after the 3-month blanking period with the exception of β-blocking agents if these were given for other indications (eg, hypertension, ischemic heart disease). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
ADT OFF
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
At the time of procedural planning, enrolled patients were randomly assigned (block randomization with center stratification) to continue (ADT ON group) or discontinue previously ineffective ADT (ADT OFF group) after the 3-month blanking period up to 1 year after ablation. In the ADT OFF group, all antiarrhythmic medications were discontinued after the 3-month blanking period with the exception of β-blocking agents if these were given for other indications (eg, hypertension, ischemic heart disease). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
ADT ON
|
||
Reporting group description |
In the ADT ON group, ADT was continued after verifying for correct dosage according to the European Society of Cardiology guidelines on the treatment of AF. If not already the case, β-blocking agents were added to Class 1C ADT. In the case of preprocedural use of amiodarone, ADT was switched to conventional class 1C or sotalol. In the ADT OFF group, all antiarrhythmic medications were discontinued after the 3-month blanking period with the exception of β-blocking agents if these were given for other indications (eg, hypertension, ischemic heart disease). | ||
Reporting group title |
ADT OFF
|
||
Reporting group description |
At the time of procedural planning, enrolled patients were randomly assigned (block randomization with center stratification) to continue (ADT ON group) or discontinue previously ineffective ADT (ADT OFF group) after the 3-month blanking period up to 1 year after ablation. In the ADT OFF group, all antiarrhythmic medications were discontinued after the 3-month blanking period with the exception of β-blocking agents if these were given for other indications (eg, hypertension, ischemic heart disease). | ||
Subject analysis set title |
Analysis of primary endpoint
|
||
Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
Except for the Kaplan-Meier survival curve and the Cox regression model, the analysis was performed in accordance to the modified intention-to-treat principle excluding patients who were lost to follow-up or died before completing the 12-month follow-up visit. Statistical tests were 2-tailed, and P≤0.05 was considered statistically significant. Analyses were conducted using SPSS, version 28.0 (IBM Corporation, Armonk, NY).
|
||
|
||||||||||
End point title |
Any documented ATA (AF, atrial flutter, or atrial tachycardia) lasting >30 seconds between 3 and 12 months of follow-up | |||||||||
End point description |
||||||||||
End point type |
Primary
|
|||||||||
End point timeframe |
Between 3 and 12 months follow-up.
|
|||||||||
|
||||||||||
Attachments |
Untitled (Filename: demolder-et-al-2023-no-effect-of-continued-antiarrhythmic-drug-treatment-on-top-of-optimized-pulmonary-vein-isolation (1).pdf) |
|||||||||
Statistical analysis title |
Kaplan Meier analysis | |||||||||
Comparison groups |
ADT ON v ADT OFF
|
|||||||||
Number of subjects included in analysis |
200
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
P-value |
= 0.797 | |||||||||
Method |
Logrank | |||||||||
Confidence interval |
||||||||||
|
||||||||||
End point title |
Number of repeat ablations | |||||||||
End point description |
||||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Between 3 and 12 months follow-up.
|
|||||||||
|
||||||||||
Attachments |
Untitled (Filename: demolder-et-al-2023-no-effect-of-continued-antiarrhythmic-drug-treatment-on-top-of-optimized-pulmonary-vein-isolation (1).pdf) |
|||||||||
Statistical analysis title |
Kaplan Meier analysis | |||||||||
Comparison groups |
ADT OFF v ADT ON
|
|||||||||
Number of subjects included in analysis |
200
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
P-value |
= 0.127 | |||||||||
Method |
Logrank | |||||||||
Parameter type |
Hazard ratio (HR) | |||||||||
Point estimate |
0.46
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
0.17 | |||||||||
upper limit |
1.25 | |||||||||
|
||||||||||
End point title |
Number of unscheduled arrhythmia-related health care provider visits | |||||||||
End point description |
||||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
3 months until 12 months follow-up.
|
|||||||||
|
||||||||||
Statistical analysis title |
Kaplan Meier analysis | |||||||||
Comparison groups |
ADT ON v ADT OFF
|
|||||||||
Number of subjects included in analysis |
200
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
P-value |
= 0.399 | |||||||||
Method |
Logrank | |||||||||
Parameter type |
Hazard ratio (HR) | |||||||||
Point estimate |
0.74
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
0.37 | |||||||||
upper limit |
1.49 | |||||||||
|
|||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From baseline until 12 month follow-up.
|
||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||
Dictionary version |
25.1
|
||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||
Reporting group title |
ADT ON
|
||||||||||||||||||||||||||||||||||||
Reporting group description |
In the ADT ON group, ADT was continued after verifying for correct dosage according to the European Society of Cardiology guidelines on the treatment of AF. If not already the case, β-blocking agents were added to Class 1C ADT. In the case of preprocedural use of amiodarone, ADT was switched to conventional class 1C or sotalol. In the ADT OFF group, all antiarrhythmic medications were discontinued after the 3-month blanking period with the exception of β-blocking agents if these were given for other indications (eg, hypertension, ischemic heart disease). | ||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
Online references |
|||
| http://www.ncbi.nlm.nih.gov/pubmed/37921006 |
|||
