Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44385   clinical trials with a EudraCT protocol, of which   7398   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Effects of low dose Aspirin in bipolar disorder – a randomized controlled trial (the A-Bipolar RCT)

    Summary
    EudraCT number
    		 2021-000862-14
    Trial protocol
    		 DK  
    Global end of trial date
    18 Nov 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    17 Feb 2026
    First version publication date
    17 Feb 2026
    Other versions
    Summary report(s)
    		 Outcome paper

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    A-bipolar
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT05035316
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Psychiatric Center Copenhagen, Frederiksberg
    Sponsor organisation address
    Nordre Fasanvej 57, Frederiksberg, Denmark, 2000
    Public contact
    Caroline Fussing Bruun, MD PhD, Copenhagen Affective Disorder research Center (CADIC), Psychiatric Center Copenhagen, 0045 52179161, caroline.fussing.bruun@regionh.dk
    Scientific contact
    Professor Lars Vedel Kessing, Copenhagen Affective Disorder research Center (CADIC), Psychiatric Center Copenhagen, 0045 38 64 70 81, caroline.fussing.bruun@regionh.dk
    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
    31 Jan 2025
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    18 Nov 2024
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Nov 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The objective of the present study is to conduct an RCT investigating whether add-on low-dose Aspirin versus placebo add-on to standard treatment improves mood stabilization and other critical patient outcomes in subjects with BD, and whether its principal effects are antimanic, antidepressant or prophylactic against relapse. Primary hypothesis: Add on low dose aspirin versus placebo to standard treatment improves mood stabilization in BD
    Protection of trial subjects
    The trial was approved by the Danish Research Ethics Committee (H-21014515) and the Danish Data Protection Agency Capital Region of Denmark (P-2021-576).
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    02 Aug 2021
    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
    Denmark: 250
    Worldwide total number of subjects
    250
    EEA total number of subjects
    250
    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)
    249
    From 65 to 84 years
    1
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Participants were recruited from two public outpatient mood disorder clinics (The Copenhagen Affective Disorder Clinics [Copenhagen and Hilleroed]) that treat the majority (> 80%) of all patients newly diagnosed with BD (within the past 2 years) in the Capital Region of Denmark. Medical doctors evaluated eligibility.

    Pre-assignment
    Screening details
    		 All patients referred to the mood disorder clinic as newly diagnosed/first episode patients with a primary diagnosis of bipolar disorder (ICD-10 classification), aged 18-65 years, were routinely asked for participation.

    Period 1
    Period 1 title
    Baseline period (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Low-dose aspirin
    Arm description
    		 150 mg acetylsalicylic acid daily
    Arm type
    		 Experimental

    Investigational medicinal product name
    Acetylsalicylic acid
    Investigational medicinal product code
    Other name
    Aspirin
    Pharmaceutical forms
    Capsule, soft
    Routes of administration
    Oral use
    Dosage and administration details
    150 mg Acetylsalicylic acid daily

    Arm title
    		 Placebo
    Arm description
    		 Capsule containing calcium
    Arm type
    		 Placebo

    Investigational medicinal product name
    Calcium
    Investigational medicinal product code
    Other name
    Placebo
    Pharmaceutical forms
    Capsule, soft
    Routes of administration
    Oral use
    Dosage and administration details

    Number of subjects in period 1
    		Low-dose aspirin Placebo
    Started
    125
    125
    Completed
    97
    103
    Not completed
    28
    22
         Consent withdrawn by subject
    1
    4
         Adverse event, non-fatal
    3
    3
         Pregnancy
    2
    2
         Unknown
    1
    -
         Diagnosis revised to unipolar depression
    1
    -
         Depression
    1
    1
         Dizziness
    1
    -
         Lost to follow-up
    10
    6
         Protocol deviation
    2
    2
         Too unstable in BD to participate
    6
    4

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Low-dose aspirin
    Reporting group description
    		 150 mg acetylsalicylic acid daily

    Reporting group title
    Placebo
    Reporting group description
    		 Capsule containing calcium

    Reporting group values
    		 Low-dose aspirin Placebo Total
    Number of subjects
    		 125 125 250
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 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)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        median (inter-quartile range (Q1-Q3))
    		 30 (25 to 37) 29 (25 to 40) -
    Gender categorical
    Units: Subjects
        Female
    		 73 72 145
        Male
    		 52 53 105
    Bipolar subtype
    Classification into type 1 or type 2
    Units: Subjects
        Type 1
    		 55 65 120
        Type 2
    		 70 60 130
    Age at BD onset
    Age when first meeting criteria for BD diagnosis
    Units: Years
        median (inter-quartile range (Q1-Q3))
    		 19 (16 to 22) 17 (15 to 20) -
    Duration of BD illness
    Number of years living with BD diagnosis
    Units: Years
        median (inter-quartile range (Q1-Q3))
    		 10 (5 to 16) 11 (6 to 20) -
    Depressive symptoms at enrollment
    Depressive symptoms rated using HDRS-17 at enrollment
    Units: HDRS-17 scale
        median (inter-quartile range (Q1-Q3))
    		 9 (6 to 14) 8 (4 to 13) -
    Manic symptoms at enrollment
    Manic symptoms at enrollment assessed using the Young Mania Rating Scale /YMRS)
    Units: YMRS score
        median (inter-quartile range (Q1-Q3))
    		 4 (2 to 8) 4 (2 to 7) -
    Functioning
    Functioning assessed using the Functioning Assessment Short Test (FAST)
    Units: FAST score
        median (inter-quartile range (Q1-Q3))
    		 16 (10 to 28) 17 (10 to 24) -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Low-dose aspirin
    Reporting group description
    		 150 mg acetylsalicylic acid daily

    Reporting group title
    Placebo
    Reporting group description
    		 Capsule containing calcium

    Primary: Mood Instability

    		 Close Top of page
    End point title
    		 Mood Instability
    End point description
    The primary endpoint was Mood Instability, calculated from time series of daily self-reported, smartphone-collected mood ratings, using the root mean square of successive differences (RMSSD) method
    End point type
    Primary
    End point timeframe
    From baseline to 6-month follow-up
    End point values
    		 Low-dose aspirin Placebo
    Number of subjects analysed
    120 [1]
    120 [2]
    Units: Mood Instability
        arithmetic mean (standard error)
    0.520 ( 0.305 )
    0.487 ( 0.324 )
    Attachments
    		 Results Table
    Notes
    [1] - 5 subjects did not report data for this endpoint
    [2] - 5 subjects did not report data for this endpoint
    Statistical analysis title
    		 Analyses of the primary endpoint
    Statistical analysis description
    For each study participant, monthly MI during follow-up was calculated using the RMSSD method when there were mood ratings for two consecutive days. The mean difference in average MI during 6-month follow-up was evaluated using a linear mixed model (LMM) including treatment group, time, and the interaction between them as fixed effects and an unstructured covariance pattern to account for repeated measurements on each participant. For exploratory purposes, monthly differences in mean MI between
    Comparison groups
    Placebo v Low-dose aspirin
    Number of subjects included in analysis
    240
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 < 0.05
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.022
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.056
         upper limit
    		 0.1
    Variability estimate
    Standard deviation
    Notes
    [3] - Linear mixed model

    Secondary: Depressive symptoms

    		 Close Top of page
    End point title
    		 Depressive symptoms
    End point description
    Change in depressive symptoms measured using the HDRS-6 scale
    End point type
    Secondary
    End point timeframe
    From baseline to 6-month follow-up
    End point values
    		 Low-dose aspirin Placebo
    Number of subjects analysed
    97
    105
    Units: HDRS-6 score
        arithmetic mean (standard deviation)
    -0.608 ( 5.17 )
    -1.22 ( 4.35 )
    Attachments
    		 Results Table
    Statistical analysis title
    		 Secondary outcome analyses
    Statistical analysis description
    Secondary outcomes were evaluated using a constrained LMM with inherent baseline adjustment including follow-up time and the constrained time-treatment interaction as fixed effects and an unstructured covariance pattern.
    Comparison groups
    Low-dose aspirin v Placebo
    Number of subjects included in analysis
    202
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 ≤ 0.05
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.195
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.23
         upper limit
    		 2.16
    Variability estimate
    Standard deviation
    Dispersion value
    0.95

    Secondary: Activity Instability

    		 Close Top of page
    End point title
    		 Activity Instability
    End point description
    Secondary outcomes included Activity Instability, calculated from daily, self-reported smartphone-collected activity ratings and evaluated by the mean monthly RMSSD
    End point type
    Secondary
    End point timeframe
    From baseline to 6-month follow-up
    End point values
    		 Low-dose aspirin Placebo
    Number of subjects analysed
    120
    120
    Units: Activity Instability
        arithmetic mean (standard deviation)
    1.37 ( 0.492 )
    1.27 ( 0.484 )
    Attachments
    		 Results Table
    Statistical analysis title
    		 Secondary outcome analyses
    Statistical analysis description
    For each study participant, monthly AI during follow-up was calculated using the RMSSD method when there were ratings for two consecutive days. The mean difference in average AI during 6-month follow-up was evaluated using a linear mixed model (LMM) including treatment group, time, and the interaction between them as fixed effects and an unstructured covariance pattern to account for repeated measurements on each participant
    Comparison groups
    Low-dose aspirin v Placebo
    Number of subjects included in analysis
    240
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 ≤ 0.05
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.111
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.019
         upper limit
    		 0.24
    Variability estimate
    Standard deviation
    Dispersion value
    0.95

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were reported from entering the trial until completion or dropout for any reason
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 -

    Reporting group title
    Low-dose aspirin
    Reporting group description
    		 -

    Serious adverse events
    		 Placebo Low-dose aspirin
    Total subjects affected by serious adverse events
         subjects affected / exposed
    12 / 125 (9.60%)
    13 / 125 (10.40%)
         number of deaths (all causes)
    0
    1
         number of deaths resulting from adverse events
    0
    0
    Psychiatric disorders
    Hospitalisation (depression)
         subjects affected / exposed
    10 / 125 (8.00%)
    9 / 125 (7.20%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hospitalisation (mania)
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 125 (0.80%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 125 (0.00%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicide
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 125 (0.80%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Endocrine disorders
    Ketoacidosis obs pro (in participant with type 1 diabetes)
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 125 (0.80%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo Low-dose aspirin
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    6 / 125 (4.80%)
    9 / 125 (7.20%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 125 (0.00%)
         occurrences all number
    1
    0
    Blood and lymphatic system disorders
    Increased bleeding tendency/bruising
         subjects affected / exposed
    1 / 125 (0.80%)
    3 / 125 (2.40%)
         occurrences all number
    1
    3
    Gastrointestinal disorders
    Nausea or vomiting
         subjects affected / exposed
    0 / 125 (0.00%)
    2 / 125 (1.60%)
         occurrences all number
    0
    2
    Reflux gastritis
         subjects affected / exposed
    4 / 125 (3.20%)
    4 / 125 (3.20%)
         occurrences all number
    4
    4

    More information

    		 Close Top of page

    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.
    Please refer to the outcome paper and Supplement (link below) for the complete reporting, including tertiary pre-specified outcomes

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/41319159
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Mon Mar 16 19:18:36 CET 2026 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA