Clinical Trial Results:
Prevention of Silent Cerebral Thromboembolism
by Oral Anticoagulation with Dabigatran
after Pulmonary Vein Isolation for Atrial Fibrillation
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Summary
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EudraCT number |
2013-003492-35 |
Trial protocol |
DE |
Global end of trial date |
15 Sep 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
02 Nov 2022
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First version publication date |
02 Nov 2022
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Other versions |
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Summary report(s) |
221004_ODIn-AF_Final Study Report_V1.0_final |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
MED2-201301
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02067182 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
University of Bonn
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Sponsor organisation address |
Venusberg Campus 1, Bonn, Germany, 53127
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Public contact |
Dr. Martin Coenen, Clinical Study Core Unit Study Center Bonn, +49 22828716045, martin.coenen@ukb.uni-bonn.de
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Scientific contact |
Dr. Martin Coenen, Clinical Study Core Unit Study Center Bonn, +49 22828716045, martin.coenen@ukb.uni-bonn.de
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
24 Feb 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
15 Sep 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
15 Sep 2020
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The purpose of the ODIn-AF study is to demonstrate that the continued administration of dabigatran for 12 months is superior in the prevention of silent cerebral embolism to discontinuation of OAC in patients free from symptomatic AF-episodes with an elevated stroke risk (CHA2DS2VASc score ≥2) after successful antral pulmonary vein ablation (and re-ablation if necessary) for paroxysmal and persistent AF.
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Protection of trial subjects |
The study medication has already been authorized for the treatment of xxx. The investigator informed the patient about the study in detail and both signed the informed consent form. A patient insurance was in place. Adverse events were documented regularly
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
08 Sep 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 200
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Worldwide total number of subjects |
200
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EEA total number of subjects |
200
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
56
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From 65 to 84 years |
144
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85 years and over |
0
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Recruitment
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Recruitment details |
The investigator examines whether all of the inclusion- and exclusion criteria are given and explains all study-related issues. The patient is included if he signs the informed consent form. Patients are included during the baseline visit prior to or until discharge after pulmonary vein ablation. | |||||||||
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Pre-assignment
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Screening details |
Written informed consent will be obtained and patients will be included in the study before or until discharge after first pulmonary vein ablation. The randomi-zation will be performed after a 3 months blanking period following antral pulmo-nary vein isolation or re-PVI for AF, followed by a 3 months observation period for AF-recurrences. During th | |||||||||
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Period 1
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Period 1 title |
overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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dabigatran | |||||||||
Arm description |
AF free patients after successful PVI receiving standard anticoagulation for 12 months with dabigatran as recommended by current guidelines | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
pradaxa
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
220 mg taken as one 110 mg capsule twice daily for patients aged 80 years or above or patients who receive concomitant verapamil
For the following groups, the daily dose of Pradaxa® of 300 mg or 220 mg should be selected based on an individual assessment of the thromboembolic risk and the risk of bleeding:
• Patients aged between 75-79 years or above
• Patients with moderate renal impairment (Cr-Cl 30-50 ml/min)
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Arm title
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no OAC | |||||||||
Arm description |
AF free patients after successful PVI. Termination of OAC after 6 months (3 months blanking period and 3 months observation period) after first or second PVI. Resumption of OAC with dabigatran in case of recurrent AF during follow up, as assessed by AF related symptoms and ECGrecording including 72h Holter ECG. | |||||||||
Arm type |
No intervention | |||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
dabigatran
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Reporting group description |
AF free patients after successful PVI receiving standard anticoagulation for 12 months with dabigatran as recommended by current guidelines | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
no OAC
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Reporting group description |
AF free patients after successful PVI. Termination of OAC after 6 months (3 months blanking period and 3 months observation period) after first or second PVI. Resumption of OAC with dabigatran in case of recurrent AF during follow up, as assessed by AF related symptoms and ECGrecording including 72h Holter ECG. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
dabigatran
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Reporting group description |
AF free patients after successful PVI receiving standard anticoagulation for 12 months with dabigatran as recommended by current guidelines | ||
Reporting group title |
no OAC
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Reporting group description |
AF free patients after successful PVI. Termination of OAC after 6 months (3 months blanking period and 3 months observation period) after first or second PVI. Resumption of OAC with dabigatran in case of recurrent AF during follow up, as assessed by AF related symptoms and ECGrecording including 72h Holter ECG. | ||
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End point title |
incidence of new micro- and macro-embolic lesions on cerebral MRI imaging incl. flare and diffusion weighted imaging | |||||||||
End point description |
The primary endpoint is assessed after a 12 months period of study therapy that begins after a postinterventional 3 months blanking period and a subsequent 3 months observation period for AF-recurrences after a first or second PVI procedure before randomization. MRI are analysed by a blinded core laboratory, facilitating rater blinded reading to therapeutic regime
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End point type |
Primary
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End point timeframe |
12 months after randomization compared to a baseline MRI at randomization.
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Attachments |
ODIn-AF_Statistical Analysis AE Listing |
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Statistical analysis title |
Primary Analysis | |||||||||
Statistical analysis description |
The primary efficacy analysis was based on the
occurrence of the primary endpoint at 12 months after the
randomization visit, which is performed 6 months after PVI. The rate
of occurrence of one of the events, which define the endpoint, was
compared between the treatment groups with a Mantel-Haenszel test
stratified for centres, at a level of 5%.
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Comparison groups |
dabigatran v no OAC
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Number of subjects included in analysis |
200
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
≤ 5 | |||||||||
Method |
Mantel-Haenszel | |||||||||
Confidence interval |
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Adverse events information [1]
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Timeframe for reporting adverse events |
All Adverse Events (AE) that occur during the study treatment until the last study visit (Visit 3) will be collected throughout the study and documented in the subject’s medical record using medical terminology and transferred to the CRF.
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Assessment type |
Systematic | |||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||
Dictionary version |
18
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Reporting groups
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Reporting group title |
dabigatran
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Reporting group description |
AF free patients after successful PVI receiving standard anticoagulation for 12 months with dabigatran as recommended by current guidelines | |||||||||||||||
Reporting group title |
no OAC
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Reporting group description |
AF free patients after successful PVI. Termination of OAC after 6 months (3 months blanking period and 3 months observation period) after first or second PVI. Resumption of OAC with dabigatran in case of recurrent AF during follow up, as assessed by AF related symptoms and ECGrecording including 72h Holter ECG. | |||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||
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| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: see attached report Experimental arm: number of non-serious adverse events: 72 number of serious adverse events: 34 Control arm: number of non-serious adverse events: 46 number of serious adverse events: 18 |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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14 Mar 2016 |
Inclusion after PVI allowed, laser ablation added, additional site added (Cologne) |
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25 Jul 2016 |
Prolongation of interval until screening-TEE, additional sites added (Bielefeld, Ludwigshafen, Göttingen), sites removed (Rostock, Lübeck), prolongation of recruitment period |
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03 Nov 2016 |
Re-PVI can be included, linear ablation procedures for makro-reentry tachycardia allowed, electroanatomical mapping not compulsory anymore, MRI for exclusion contraindications for OAC at randomization added, additional site added (Wuppertal) |
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27 Jan 2017 |
Analysis of dispensable laboratory parameters removed (ANP, BNP, NTproBNP, CRP), additional sites added (Munich, Karlsruhe) |
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19 Sep 2017 |
Prolongation of time between Holter and randomization from 7 to 14 days, new sIMPD (changed colour of IMP-capsules), new SmPC (17.01.2013), site removed (Frankfurt) |
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30 Jul 2019 |
new SmPC (January 2018) |
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13 Nov 2019 |
new SmPC (May 2019) |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
