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   43865   clinical trials with a EudraCT protocol, of which   7286   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:
    Evaluation of the relationship between effervescent acetaminophen and blood pressure. A clinical trial.

    Summary
    EudraCT number
    		 2010-023485-53
    Trial protocol
    		 ES  
    Global end of trial date
    29 Mar 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    29 Jun 2022
    First version publication date
    29 Jun 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    IJG-PAR-2010
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02514538
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    IDIAP Jordi Gol
    Sponsor organisation address
    Gran Via de les Corts Catalanes, 587, Barcelona, Spain, 08007
    Public contact
    Ana Garcia-Sangenis, IDIAP Jordi Gol - UEM, +34 934824644, agarcia@idiapjgol.org
    Scientific contact
    Ana Garcia-Sangenis, IDIAP Jordi Gol - UEM, +34 934824644, agarcia@idiapjgol.org
    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
    29 Mar 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    29 Mar 2016
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Mar 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the effect on blood pressure of effervescent paracetamol compared to non-effervescent paracetamol, in hypertensive patients.
    Protection of trial subjects
    Routine care. As recommended for second-line analgesic treatment, 50-mg tramadol every 8 h was permitted if pain persisted at a level more than 3 on the VAS.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    09 Feb 2012
    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: 49
    Worldwide total number of subjects
    49
    EEA total number of subjects
    49
    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)
    12
    From 65 to 84 years
    37
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Recruitment period: February 2012 - June 2014 (Catalonia, Spain). Primary Health Care Sites Multicenter, randomized, controlled, cross-over, open, phase IV clinical trial.

    Pre-assignment
    Screening details
    		 Wash out period of 3-15 days before first treatment period. During the washout periods, tramadol was the only analgesic allowed. Patients included in the study were older than 18 years, with hypertension, chronic osteoarticular pain, and usual need of analgesic treatment. 59 patients were screened for eligibility, 10 were not randomized.

    Pre-assignment period milestones
    Number of subjects started
    		 59 [1]
    Number of subjects completed
    		 49

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 not give informed consent: 5
    Reason: Number of subjects
    		 non compliance with inclusion criteria: 5
    Notes
    [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: 10 patients are screened but not enrolled
    Period 1
    Period 1 title
    Randomisation and Treatment (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 AB - Effervescent - Non effervescent
    Arm description
    		 Wash out period (3-15 days) / Effervescent paracetamol 3 weeks/wash out period (3-15 days) / non-effervescent paracetamol 3 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    Paracetamol
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral powder in sachet, Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    period A: 1g effervescent paracetamol (oral powder in sachet) every 8h during 3 weeks period B: 1g non-effervescent paracetamol (tablet) every 8h during 3 weeks

    Arm title
    		 BA - Non effervescent - effervescent
    Arm description
    		 Wash out period (3-15 days) / Non- Effervescent paracetamol 3 weeks/wash out period (3-15 days) / Effervescent paracetamol 3 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    Paracetamol
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral powder in sachet, Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Paracetamol (tablet) 1 gram every 8 hours during 3 weeks. Paracetamol (oral effervescent powder) 1 gram every 8 hours during 3 weeks

    Number of subjects in period 1
    		AB - Effervescent - Non effervescent BA - Non effervescent - effervescent
    Started
    24
    25
    Completed
    14
    21
    Not completed
    10
    4
         Consent withdrawn by subject
    1
    -
         Adverse event, non-fatal
    1
    -
         Lost to follow-up
    1
    -
         Protocol deviation
    7
    4

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    AB - Effervescent - Non effervescent
    Reporting group description
    		 Wash out period (3-15 days) / Effervescent paracetamol 3 weeks/wash out period (3-15 days) / non-effervescent paracetamol 3 weeks

    Reporting group title
    BA - Non effervescent - effervescent
    Reporting group description
    		 Wash out period (3-15 days) / Non- Effervescent paracetamol 3 weeks/wash out period (3-15 days) / Effervescent paracetamol 3 weeks

    Reporting group values
    		 AB - Effervescent - Non effervescent BA - Non effervescent - effervescent Total
    Number of subjects
    		 24 25 49
    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
        arithmetic mean (standard deviation)
    		 66.8 ( 9.6 ) 67.1 ( 8.3 ) -
    Gender categorical
    Units: Subjects
        Female
    		 18 20 38
        Male
    		 6 5 11

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    AB - Effervescent - Non effervescent
    Reporting group description
    		 Wash out period (3-15 days) / Effervescent paracetamol 3 weeks/wash out period (3-15 days) / non-effervescent paracetamol 3 weeks

    Reporting group title
    BA - Non effervescent - effervescent
    Reporting group description
    		 Wash out period (3-15 days) / Non- Effervescent paracetamol 3 weeks/wash out period (3-15 days) / Effervescent paracetamol 3 weeks

    Subject analysis set title
    Effervescent paracetamol
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All subjects that have initiated effervescent paracetamol treatment.

    Subject analysis set title
    Non-Effervescent paracetamol
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All patients that have initiated non effervescent paracetamol treatment

    Primary: Increase in 24h Systolic Blood Pressure (SBP)

    		 Close Top of page
    End point title
    		 Increase in 24h Systolic Blood Pressure (SBP)
    End point description
    Crossover study. Difference in 24h SBP when 3 weeks treatment of non effervescent paracetamol vs 3 weeks treatment of effervescent paracetamol. In the ITT analysis, treatment with effervescent paracetamol was associated with an increase of 3.59mmHg (95% CI 1.39–5.79; P=0.003) in 24-h SBP, and noneffervescent paracetamol with a 0.33-mmHg reduction (95% CI -1.78 to -1.13; P=0.886); the difference in 24-h SBP between the two treatments was 3.99mmHg (95% CI 1.35–6.63; P=0.004), higher in the effervescent paracetamol treatment periods. Similarly, the per-protocol analysis showed an increase of 4.57mmHg in 24-h SBP (95% CI 2.01–7.13) under effervescent paracetamol treatment and a reduction of 0.21mmHg (95% CI -2.12 to -1.71; P=0.009) at the end of noneffervescent paracetamol treatment. The difference in 24-h SBP between the two groups was 5.04mmHg (95% CI 1.80–8.28; P=0.004).
    End point type
    Primary
    End point timeframe
    3 weeks
    End point values
    		 Effervescent paracetamol Non-Effervescent paracetamol
    Number of subjects analysed
    46
    41
    Units: mmHG
        number (confidence interval 95%)
    3.59 (1.39 to 5.79)
    -0.33 (-1.78 to 1.13)
    Statistical analysis title
    		 Intention to Treat
    Statistical analysis description
    CROSSOVER DESIGN. Total number of patients 46. All both arms of treatment. We estimated the sample size for a crossover trial with the aim to detect a mean difference in 24-h SBP greater than 2mmHg (minimum clinically relevant difference) assuming a SD of 4.5mmHg. With a two-sided alpha error of 5%, we estimated that 49 patients would need to be enrolled to have a statistical power of 80% considering 15% of dropout rate.
    Comparison groups
    Non-Effervescent paracetamol v Effervescent paracetamol
    Number of subjects included in analysis
    87
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 = 5
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 11
    Variability estimate
    Standard deviation
    Dispersion value
    4.5
    Notes
    [1] - Main and secondary analysis was carried out on an intention-to-treat (ITT) basis with patients who fulfilled all the eligibility criteria and had a measurement of the primary outcome at the baseline visit.

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    All study period.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18
    Reporting groups
    Reporting group title
    Effervescent paracetamol
    Reporting group description
    		 -

    Reporting group title
    Non-Effervescent paracetamol
    Reporting group description
    		 -

    Serious adverse events
    		 Effervescent paracetamol Non-Effervescent paracetamol
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 41 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Effervescent paracetamol Non-Effervescent paracetamol
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    7 / 46 (15.22%)
    4 / 41 (9.76%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 46 (4.35%)
    1 / 41 (2.44%)
         occurrences all number
    2
    1
    Dizziness
         subjects affected / exposed
    2 / 46 (4.35%)
    1 / 41 (2.44%)
         occurrences all number
    2
    1
    Vertigo
         subjects affected / exposed
    2 / 46 (4.35%)
    2 / 41 (4.88%)
         occurrences all number
    2
    2
    Respiratory, thoracic and mediastinal disorders
    Nasopharyngitis
    Additional description: Common cold
         subjects affected / exposed
    3 / 46 (6.52%)
    0 / 41 (0.00%)
         occurrences all number
    4
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    01 Jun 2011
    New sites
    03 Oct 2011
    New sites
    02 Aug 2012
    New sites
    01 Feb 2013
    New sites
    08 May 2013
    New sites

    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.
    Only main results included. See paper for more specified information.

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/29570512
    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-Sun Apr 28 22:36:48 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA