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   43857   clinical trials with a EudraCT protocol, of which   7284   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:
    A multicenter randomised opened study to assess the efficacy and safety of the withdrawal of nucleos/tide analogues in HIV-1-infected subjects with complete or intermediate resistance to these analogues, multitreated with virological suppression

    Summary
    EudraCT number
    		 2012-000198-21
    Trial protocol
    		 ES  
    Global end of trial date
    15 Oct 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    14 Aug 2016
    First version publication date
    14 Aug 2016
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    NUKE-OUT
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Fundació Lluita contra la SIDA
    Sponsor organisation address
    crta. de canyet s/n, Badalona, Spain, 08916
    Public contact
    CRA, Fundació Lluita contra la SIDA, +34 93497 84 14, jtoro@flsida.org
    Scientific contact
    CRA, Fundació Lluita contra la SIDA, +34 93497 84 14, jtoro@flsida.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
    15 Oct 2014
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    15 Oct 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Oct 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the safety and efficacy at 48 weeks of withdrawing NRTIs with intermediate or complete resistance in subjects with previous virological failure and a suppressed viral load for > 6 months.
    Protection of trial subjects
    No specific measures.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 May 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: 90
    Worldwide total number of subjects
    90
    EEA total number of subjects
    90
    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)
    90
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Of 92 subjects screened, 90 were randomized and treated (experimental, n=45; and control, n=45)

    Period 1
    Period 1 title
    overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 experimental
    Arm description
    		 stop NRTIs without complete activity, either one or both.
    Arm type
    		 Experimental

    Investigational medicinal product name
    NRTIs + PI
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    multidrug salvage regimen with at least two active drugs (one a boosted PI)

    Arm title
    		 control
    Arm description
    		 maintain the treatment unchanged
    Arm type
    		 control

    Investigational medicinal product name
    NRTIs + PI
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    multidrug salvage regimen with at least two active drugs (one a boosted PI)

    Number of subjects in period 1
    		experimental control
    Started
    45
    45
    Completed
    44
    44
    Not completed
    1
    1
         Adverse event, non-fatal
    1
    -
         discontinued study drug due to other reasons
    -
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    experimental
    Reporting group description
    		 stop NRTIs without complete activity, either one or both.

    Reporting group title
    control
    Reporting group description
    		 maintain the treatment unchanged

    Reporting group values
    		 experimental control Total
    Number of subjects
    		 45 45 90
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 45 45 90
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 52 ( 7.3 ) 49.2 ( 6.4 ) -
    Gender categorical
    Units: Subjects
        Female
    		 4 14 18
        Male
    		 41 31 72

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    experimental
    Reporting group description
    		 stop NRTIs without complete activity, either one or both.

    Reporting group title
    control
    Reporting group description
    		 maintain the treatment unchanged

    Primary: proportion HIV-1 RNA < 50 copies/mL

    		 Close Top of page
    End point title
    		 proportion HIV-1 RNA < 50 copies/mL
    End point description
    End point type
    Primary
    End point timeframe
    week 48
    End point values
    		 experimental control
    Number of subjects analysed
    45
    45
    Units: people
    41
    44
    Statistical analysis title
    		 Primary efficacy analysis
    Statistical analysis description
    The primary efficacy analysis used the ITT-exposed population (patients who had received at least one dose of study medication). The trial was designed to show non-inferior efficacy of the experimental arm at week 48 (non-inferiority margin: -12%)
    Comparison groups
    experimental v control
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 > 0.05 [1]
    Method
    		 confidence interval 95%
    Confidence interval
    Notes
    [1] - adjusted treatment difference: 26.7%; 95% CI: -17.4, 4.1);

    Secondary: rate of virological failure

    		 Close Top of page
    End point title
    		 rate of virological failure
    End point description
    End point type
    Secondary
    End point timeframe
    week 48
    End point values
    		 experimental control
    Number of subjects analysed
    45
    45
    Units: people
    1
    0
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    week 48
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 DAIDS AE GRADING TAB
    Dictionary version
    2.0
    Reporting groups
    Reporting group title
    experimental
    Reporting group description
    		 -

    Reporting group title
    control
    Reporting group description
    		 -

    Serious adverse events
    		 experimental control
    Total subjects affected by serious adverse events
         subjects affected / exposed
    6 / 45 (13.33%)
    5 / 45 (11.11%)
         number of deaths (all causes)
    1
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    lung carcinoma
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    uterine cervical carcinoma
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Hepatic encephalopathy
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Giardia lamblia enterocolitis
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    cirrhotic ascite
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    bacterial pneumonia
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Death
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Syphilis
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         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: 1%
    Non-serious adverse events
    		 experimental control
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    25 / 45 (55.56%)
    20 / 45 (44.44%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Memory impairment
         subjects affected / exposed
    2 / 45 (4.44%)
    0 / 45 (0.00%)
         occurrences all number
    2
    0
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    Haematinuria
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    glycemia increase
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    Proteinuria
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    iron deficiency anaemia
         subjects affected / exposed
    0 / 45 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    0
    2
    Social circumstances
    Anxiety
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Gastrointestinal disorder
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    Diarrhoea
         subjects affected / exposed
    2 / 45 (4.44%)
    0 / 45 (0.00%)
         occurrences all number
    2
    0
    Gastrointestinal
         subjects affected / exposed
    0 / 45 (0.00%)
    3 / 45 (6.67%)
         occurrences all number
    0
    3
    Renal and urinary disorders
    Urinary tract infection
         subjects affected / exposed
    3 / 45 (6.67%)
    0 / 45 (0.00%)
         occurrences all number
    3
    0
    Endocrine disorders
    Diabetes mellitus
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Tendinous contracture
         subjects affected / exposed
    2 / 45 (4.44%)
    0 / 45 (0.00%)
         occurrences all number
    2
    0
    Myalgia
         subjects affected / exposed
    2 / 45 (4.44%)
    0 / 45 (0.00%)
         occurrences all number
    2
    0
    Infections and infestations
    malar infection
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    Respiratory disorder
         subjects affected / exposed
    5 / 45 (11.11%)
    0 / 45 (0.00%)
         occurrences all number
    5
    0
    Hepatitis C
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    Urinary infection
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    19 Mar 2012
    Protocol, Patient Information and Informed consent, protocol summary and first submission modifications
    24 Oct 2012
    Oral patient Informatio oral and witness informed consent
    28 Jan 2013
    inclusion of a new trial site
    22 Apr 2013
    inclusion of a new trial site

    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
    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-Thu Apr 25 07:32:57 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA