Clinical Trial Results:
Apixaban for treatment of embolic stroke of undetermined source
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Summary
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EudraCT number |
2014-005109-19 |
Trial protocol |
DE |
Global end of trial date |
09 Nov 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
26 May 2023
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First version publication date |
26 May 2023
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Other versions |
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Summary report(s) |
Atticus-Trial_ Final_Report |
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 |
ATTICUS
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
University Hospital Tübingen
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Sponsor organisation address |
Otfried-Müller-Strasse 10, Tübingen, Germany, 72076
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Public contact |
Prof. Dr. med. Tobias Geisler : Principal Investigator (PI) and Coordinating Investigator, University Hospital Tuebingen, tobias.geisler@med.uni-tuebingen.de
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Scientific contact |
Prof. Dr. med. Tobias Geisler : Principal Investigator (PI) and Coordinating Investigator, University Hospital Tuebingen, tobias.geisler@med.uni-tuebingen.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 |
09 Dec 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
09 Nov 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
09 Nov 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary endpoint was the occurrence of at least one new ischemic lesion identified by magnetic resonance imaging (axial T2-weighted fluid attenuated inversion recovery MRI (FLAIR) and/or axial diffusion weighted MRI (DWI)) at 12 months when compared to the baseline MRI (FLAIR, DWI) obtained at the time of study drug initiation. MRI at 12 months was directly compared with the baseline MRI to assess for new ischemic lesions.
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Protection of trial subjects |
The procedures set out in this trial protocol, pertaining to the conduct, evaluation, and documentation of this trial, are designed to ensure that all persons involved in the trial act according to Good Clinical Practice (GCP) and the ethical principles described in the applicable version of the Declaration of Helsinki. This is a scientific clinical study; the German Medicines Act (AMG) §40 is applicable without restrictions according to section §42.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
05 Feb 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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: 352
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Worldwide total number of subjects |
352
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EEA total number of subjects |
352
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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) |
352
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The general criteria for subject selection was adult male and female patients with ESUS. | |||||||||
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Pre-assignment
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Screening details |
Aproximately 900 patients were screened. Actually 371 patients were recruited and 353 were randomized. Then there were 18 drop-outs and 1 patient who withdrew the consent on randomization day. | |||||||||
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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 | |||||||||
Blinding implementation details |
N.a.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Apixaban | |||||||||
Arm description |
Apixaban was administered from randomization (depending on the severity of stroke and the individual risk for HTI (3-28 days after minor/moderate stroke and 14-28 days after major stroke) until 12 months after study drug initiation. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Apixaban
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Investigational medicinal product code |
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Other name |
Eliquis
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
5 mg, or reduced dose of 2.5 mg in patients who meet two of the following three criteria: 1. age ≥ 80 years, 2. body weight < 60 kg and 3. serum creatinin ≥ 1,5 mg/dl (133 Micromol/L)
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Arm title
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Acetylsalicylic acid (ASS) | |||||||||
Arm description |
Usual care (acetylsalicylic acid) were administered from study drug initiation (3-28 days after minor/moderate stroke and 14-28 days after major stroke) until 12 months after study drug initiation. | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Acetylsalicylic acid
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Investigational medicinal product code |
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Other name |
ASS
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Dose: 100 mg
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Apixaban
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Reporting group description |
Apixaban was administered from randomization (depending on the severity of stroke and the individual risk for HTI (3-28 days after minor/moderate stroke and 14-28 days after major stroke) until 12 months after study drug initiation. | ||
Reporting group title |
Acetylsalicylic acid (ASS)
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Reporting group description |
Usual care (acetylsalicylic acid) were administered from study drug initiation (3-28 days after minor/moderate stroke and 14-28 days after major stroke) until 12 months after study drug initiation. | ||
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End point title |
The occurrence of at least one new ischemic lesion | |||||||||
End point description |
The primary endpoint was the occurrence of at least one new ischemic lesion identified by magnetic resonance imaging (axial T2-weighted fluid attenuated inversion recovery MRI (FLAIR) and/or axial diffusion weighted MRI (DWI)) at 12 months when compared to the baseline MRI (FLAIR, DWI) obtained at the time of study drug initiation. MRI at 12 months was directly compared with the baseline MRI to assess for new ischemic lesions.
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End point type |
Primary
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End point timeframe |
12 months
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Statistical analysis title |
Analysis of primary endpoint | |||||||||
Comparison groups |
Apixaban v Acetylsalicylic acid (ASS)
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Number of subjects included in analysis |
325
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | |||||||||
P-value |
= 0.57 [1] | |||||||||
Method |
t-test, 2-sided | |||||||||
Confidence interval |
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95% | |||||||||
sides |
2-sided
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lower limit |
0.68 | |||||||||
upper limit |
2.37 | |||||||||
Variability estimate |
Standard deviation
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| Notes [1] - p-value = 0.57 two-sided |
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End point title |
Combination of recurrent ischemic stroke, hemorrhagic stroke and systemic embolism | |||||||||
End point description |
Combination of recurrent ischemic stroke, hemorrhagic stroke and systemic embolism
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End point type |
Secondary
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End point timeframe |
12 months
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| No statistical analyses for this end point | ||||||||||
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End point title |
Combination of major adverse cardiovascular events (MACE) including recurrentstroke, myocardial infarction and cardiovascular death | |||||||||
End point description |
Combination of major adverse cardiovascular events (MACE) including recurrent stroke, myocardial infarction and cardiovascular death.
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End point type |
Secondary
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End point timeframe |
12 months
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| No statistical analyses for this end point | ||||||||||
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End point title |
Combination of major adverse cardiovascular events (MACE) including recurrentstroke, myocardial infarction without cardiovascular death | |||||||||
End point description |
Combination of major adverse cardiovascular events (MACE) including recurrent stroke, myocardial infarction without cardiovascular deaths.
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End point type |
Secondary
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End point timeframe |
12 months
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| No statistical analyses for this end point | ||||||||||
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End point title |
Combinationof major and clinically relevant non-major bleedings | |||||||||
End point description |
Combination of major and clinically relevant non-major bleedings defined according to ISTH criteria
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End point type |
Secondary
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End point timeframe |
12 months
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| No statistical analyses for this end point | ||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
All SAEs must be collected that occur from initiation of study drug and within 30 days of discontinuing dosing.
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Assessment type |
Non-systematic | ||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||
Dictionary version |
0
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| Frequency threshold for reporting non-serious adverse events: 0% | |||
| 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: Detail on Safety Data such as Adverse Events and Serious Adverse Events can be found in the Appendix of the summary attached. |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
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 | |||
