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:
    Long-term (3 years) ophthalmic safety and cardiac efficacy and safety of ivabradine administered orally at the therapeutic doses (2.5/5/7.5 mg b.i.d.) on top of anti-anginal background therapy, to patients with chronic stable angina pectoris. An international, double-blind placebo controlled study.

    Due to the EudraCT – Results system being out of service between 31 July 2015 and 12 January 2016, these results have been published in compliance with revised timelines.
    Summary
    EudraCT number
    		 2006-005475-17
    Trial protocol
    		 IE   PT   BE   FI   GB   HU   SE   DE  
    Global end of trial date
    12 Feb 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    02 Mar 2016
    First version publication date
    02 Mar 2016
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CL3-16257-067
    Additional study identifiers
    ISRCTN number
    		 ISRCTN99185656
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Institut de Recherches Internationales Servier
    Sponsor organisation address
    50 rue carnot, Suresnes, France,
    Public contact
    ITP (Innovative Therapeutic Pole), Institut de Recherches Internationales Servier, +33 1 55 72 43 66, clinicaltrials@servier.com
    Scientific contact
    ITP (Innovative Therapeutic Pole), Institut de Recherches Internationales Servier, +33 1 55 72 43 66, clinicaltrials@servier.com
    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
    12 Feb 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    12 Feb 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    12 Feb 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To document the absence of retinal toxicity of ivabradine versus placebo in chronic stable angina patients after treatment cessation in the subset of patients with emergent bilateral relevant ERG abnormalities observed at 36 months under treatment. Consequently, the main endpoint of the study was a safety endpoint.
    Protection of trial subjects
    The study was conducted in accordance with the ethical principles stated in the Declaration of Helsinki, 1964, as revised in Seoul 2008. Mandatory withdrawal from the study if study drug not tolerated, prolonged loss of sinus rhythm, occurence of condition preventing the assessment of visual function or morphology , condition or treatment of the visual system which irreversibly reduced visual function beyond that reasonably attributable to age and/or established underlying condition such as diabetes, pregnancy. Other criteria for premature withdrawal of the study: adverse event requiring discontinuation of study drug and/or administration of an unauthorized concomitant treatment.
    Background therapy
    		 Standard anti-anginal therapies.
    Evidence for comparator
    		 Not applicable
    Actual start date of recruitment
    29 Apr 2008
    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
    Portugal: 16
    Country: Number of subjects enrolled
    Sweden: 5
    Country: Number of subjects enrolled
    Belgium: 4
    Country: Number of subjects enrolled
    Finland: 7
    Country: Number of subjects enrolled
    Hungary: 18
    Country: Number of subjects enrolled
    Ireland: 1
    Country: Number of subjects enrolled
    Australia: 15
    Country: Number of subjects enrolled
    Singapore: 3
    Country: Number of subjects enrolled
    Argentina: 28
    Worldwide total number of subjects
    97
    EEA total number of subjects
    51
    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)
    45
    From 65 to 84 years
    52
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Study population was male or female with chronic stable angina pectoris, with reliable baseline electroretinogram and visual fields (static and kinetic), in stable condition regarding the angina symptoms and related treatments, in sinus rhythm and with a resting HR ≥ 60 bpm.

    Period 1
    Period 1 title
    Double-blind treatment period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator
    Blinding implementation details
    Treatment randomisation and allocation centralized (interactive system response). Study products of identical appearance.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Ivabradine
    Arm description
    		 -
    Arm type
    		 test drug

    Investigational medicinal product name
    Ivabradine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Starting dose of 5 mg twice daily or 2.5 mg twice daily (patients > 75 years and/or with concomitant treatment with moderate CYP3A4 inhibitors). During this period, highest dose was 7.5 mg twice daily and lowest dose 2.5 mg twice daily.

    Arm title
    		 Placebo
    Arm description
    		 -
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One placebo tablet (matching ivabradine tablet) twice daily.

    Number of subjects in period 1
    		Ivabradine Placebo
    Started
    50
    47
    Completed
    39
    37
    Not completed
    11
    10
         Adverse event, serious fatal
    1
    1
         Consent withdrawn by subject
    5
    4
         Adverse event, non-fatal
    5
    4
         Lost to follow-up
    -
    1
    Period 2
    Period 2 title
    Run-out
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Single blind
    Roles blinded
    		 Subject

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 All patients who completed the double blind treatment period (3-years) entered in the run-out period (2 months) during which they received placebo.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One placebo tablet (matching ivabradine tablet) twice daily.

    Arm title
    		 Placebo
    Arm description
    		 All patients who completed the double blind treatment period (3-years) entered in the run-out period (2 months) during which they received placebo.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One placebo tablet (matching ivabradine tablet) twice daily.

    Number of subjects in period 2
    		Placebo Placebo
    Started
    39
    37
    Completed
    39
    37

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Ivabradine
    Reporting group description
    		 -

    Reporting group title
    Placebo
    Reporting group description
    		 -

    Reporting group values
    		 Ivabradine Placebo Total
    Number of subjects
    		 50 47 97
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 24 21 45
        From 65-84 years
    		 26 26 52
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 63.4 ( 7.8 ) 63.6 ( 8.2 ) -
    Gender categorical
    Units: Subjects
        Female
    		 21 19 40
        Male
    		 29 28 57

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Ivabradine
    Reporting group description
    		 -

    Reporting group title
    Placebo
    Reporting group description
    		 -
    Reporting group title
    Placebo
    Reporting group description
    		 All patients who completed the double blind treatment period (3-years) entered in the run-out period (2 months) during which they received placebo.

    Reporting group title
    Placebo
    Reporting group description
    		 All patients who completed the double blind treatment period (3-years) entered in the run-out period (2 months) during which they received placebo.

    Subject analysis set title
    Sub-Safety Ophthalmic Set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    For the ophthalmic (OPH) safety analyses, a Safety Ophthalmic Set (SOS) was defined as all patients having received at least one dose of study drug and with at least one evaluation from at least one reliable OPH test (ERG, visual field ...) for each eye at baseline and at M36 (after 3-years of treatment) under treatment or at M38 (i.e. two months after treatment cessation). The SSOS was defined as all patients of the SOS with a bilateral relevant ERG abnormality at M36 under treatment on at least one of the four main ERG criteria (composite endpoint) and a reliable ERG test at M36 under treatment for each eye and at M38.

    Primary: Bilateral relevant ERG abnormality

    		 Close Top of page
    End point title
    		 Bilateral relevant ERG abnormality
    End point description
    Four main ERG criteria were defined as following: Standard combined rod/cone response (3RC) a- and b-waves, amplitude. ­Standard combined rod/cone response (3RC) a- and b-waves, implicit time. Single flash cone response (SFC) a- and b-waves, amplitude. Single flash cone response (SFC) a- and b-waves, implicit time.
    End point type
    Primary
    End point timeframe
    In patients with at least one bilateral relevant abnormality at M36 under treatment (SSOS, N = 5), presence (yes/no) of a bilateral relevant abnormality at M38 on at least one of the four main ERG criteria.
    End point values
    		 Ivabradine Placebo Sub-Safety Ophthalmic Set
    Number of subjects analysed
    2 [1]
    3 [2]
    5
    Units: number of patients
    0
    1
    1
    Notes
    [1] - Both patients had a single ERG response affected at M36.
    [2] - Each of these 3 patients had several ERG responses/components affected at M36.
    Statistical analysis title
    		 Primary composite safety endpoint
    Statistical analysis description
    Estimate of the diffference between the two groups was given using 95% CI based on the Wilson score method .
    Comparison groups
    Ivabradine v Placebo
    Number of subjects included in analysis
    5
    Analysis specification
    Pre-specified
    Analysis type
    		 other [3]
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -33.33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -87.69
         upper limit
    		 52.87
    Notes
    [3] - To estimate the difference between ivrabradine anbd placebo on an incidence rate (bilateral relevant ERG abnormality after treatment cessation at M36) using a non-parametric approach.

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were reported all over the study. Adverse events reported over the 3-year double-blind treatment period in patients who received at least one dose of study drug are presented here as it was the only period when patients received ivabradine.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.0
    Reporting groups
    Reporting group title
    Ivabradine
    Reporting group description
    		 -

    Reporting group title
    Placebo
    Reporting group description
    		 -

    Serious adverse events
    		 Ivabradine Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    21 / 50 (42.00%)
    19 / 47 (40.43%)
         number of deaths (all causes)
    1
    1
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Colon adenoma
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endometrial stromal sarcoma
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Invasive ductal breast carcinoma
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemodynamic instability
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Gastric banding
         subjects affected / exposed
    0 / 50 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    1 / 50 (2.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypothermia
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Local swelling
         subjects affected / exposed
    0 / 50 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multi-organ failure
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Sudden cardiac death
         subjects affected / exposed
    0 / 50 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 50 (0.00%)
    2 / 47 (4.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adenomyosis
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 50 (2.00%)
    2 / 47 (4.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    2 / 50 (4.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchospasm
         subjects affected / exposed
    0 / 50 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 50 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary fibrosis
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Pulmonary function test decreased
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Alcohol poisoning
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 50 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incisional hernia
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haematuria
         subjects affected / exposed
    0 / 50 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    0 / 50 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Angina unstable
         subjects affected / exposed
    2 / 50 (4.00%)
    6 / 47 (12.77%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    2 / 50 (4.00%)
    2 / 47 (4.26%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute coronary syndrome
         subjects affected / exposed
    0 / 50 (0.00%)
    2 / 47 (4.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    2 / 50 (4.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 50 (2.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular extrasystoles
         subjects affected / exposed
    2 / 50 (4.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    aortic valve stenosis
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bundle branch block right
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    sick sinus syndrome
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus arrest
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    syncope
         subjects affected / exposed
    2 / 50 (4.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid artery stenosis
         subjects affected / exposed
    0 / 50 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 50 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 50 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertebrobasilar insufficiency
         subjects affected / exposed
    0 / 50 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 50 (4.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis ischaemic
         subjects affected / exposed
    0 / 50 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum intestinal
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 50 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Nephrolithiasis
         subjects affected / exposed
    0 / 50 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 50 (2.00%)
    2 / 47 (4.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 50 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoporotic fracture
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 50 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    2 / 50 (4.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 50 (2.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial infection
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis salmonella
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes simplex encephalitis
         subjects affected / exposed
    0 / 50 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    0 / 50 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Ophthalmic herpes zoster
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Lactic acidosis
         subjects affected / exposed
    1 / 50 (2.00%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 4%
    Non-serious adverse events
    		 Ivabradine Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    40 / 50 (80.00%)
    37 / 47 (78.72%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    6 / 50 (12.00%)
    9 / 47 (19.15%)
         occurrences all number
    7
    10
    Hypotension
         subjects affected / exposed
    2 / 50 (4.00%)
    2 / 47 (4.26%)
         occurrences all number
    2
    2
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    1 / 50 (2.00%)
    2 / 47 (4.26%)
         occurrences all number
    1
    2
    Oedema peripheral
         subjects affected / exposed
    3 / 50 (6.00%)
    0 / 47 (0.00%)
         occurrences all number
    3
    0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    2 / 50 (4.00%)
    0 / 47 (0.00%)
         occurrences all number
    2
    0
    Cough
         subjects affected / exposed
    0 / 50 (0.00%)
    2 / 47 (4.26%)
         occurrences all number
    0
    2
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 50 (2.00%)
    3 / 47 (6.38%)
         occurrences all number
    1
    3
    Depression
         subjects affected / exposed
    0 / 50 (0.00%)
    3 / 47 (6.38%)
         occurrences all number
    0
    3
    Insomnia
         subjects affected / exposed
    3 / 50 (6.00%)
    0 / 47 (0.00%)
         occurrences all number
    3
    0
    Investigations
    Heart rate decreased
         subjects affected / exposed
    5 / 50 (10.00%)
    2 / 47 (4.26%)
         occurrences all number
    5
    2
    Blood pressure increased
         subjects affected / exposed
    1 / 50 (2.00%)
    2 / 47 (4.26%)
         occurrences all number
    2
    4
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    2 / 50 (4.00%)
    2 / 47 (4.26%)
         occurrences all number
    2
    4
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    6 / 50 (12.00%)
    6 / 47 (12.77%)
         occurrences all number
    6
    7
    Atrial fibrillation
         subjects affected / exposed
    1 / 50 (2.00%)
    3 / 47 (6.38%)
         occurrences all number
    2
    3
    Cardiac failure
         subjects affected / exposed
    1 / 50 (2.00%)
    2 / 47 (4.26%)
         occurrences all number
    1
    3
    Palpitations
         subjects affected / exposed
    0 / 50 (0.00%)
    2 / 47 (4.26%)
         occurrences all number
    0
    2
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    4 / 50 (8.00%)
    3 / 47 (6.38%)
         occurrences all number
    5
    3
    Headache
         subjects affected / exposed
    1 / 50 (2.00%)
    2 / 47 (4.26%)
         occurrences all number
    1
    3
    Eye disorders
    Cataract
         subjects affected / exposed
    6 / 50 (12.00%)
    3 / 47 (6.38%)
         occurrences all number
    7
    3
    Cataract nuclear
         subjects affected / exposed
    3 / 50 (6.00%)
    0 / 47 (0.00%)
         occurrences all number
    3
    0
    Photopsia
         subjects affected / exposed
    4 / 50 (8.00%)
    2 / 47 (4.26%)
         occurrences all number
    4
    2
    Conjunctivitis allergic
         subjects affected / exposed
    0 / 50 (0.00%)
    2 / 47 (4.26%)
         occurrences all number
    0
    2
    Blepharitis
         subjects affected / exposed
    2 / 50 (4.00%)
    1 / 47 (2.13%)
         occurrences all number
    2
    1
    Dry eye
         subjects affected / exposed
    3 / 50 (6.00%)
    1 / 47 (2.13%)
         occurrences all number
    3
    2
    Eyelid disorder
         subjects affected / exposed
    0 / 50 (0.00%)
    2 / 47 (4.26%)
         occurrences all number
    0
    2
    Gastrointestinal disorders
    Gastrooesophageal reflux disease
         subjects affected / exposed
    2 / 50 (4.00%)
    1 / 47 (2.13%)
         occurrences all number
    2
    1
    Vomiting
         subjects affected / exposed
    3 / 50 (6.00%)
    0 / 47 (0.00%)
         occurrences all number
    3
    0
    Abdominal pain upper
         subjects affected / exposed
    2 / 50 (4.00%)
    0 / 47 (0.00%)
         occurrences all number
    2
    0
    Constipation
         subjects affected / exposed
    0 / 50 (0.00%)
    2 / 47 (4.26%)
         occurrences all number
    0
    2
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    2 / 50 (4.00%)
    0 / 47 (0.00%)
         occurrences all number
    2
    0
    Musculoskeletal and connective tissue disorders
    Osteoarthritis
         subjects affected / exposed
    0 / 50 (0.00%)
    4 / 47 (8.51%)
         occurrences all number
    0
    4
    Myalgia
         subjects affected / exposed
    3 / 50 (6.00%)
    0 / 47 (0.00%)
         occurrences all number
    3
    0
    Arthralgia
         subjects affected / exposed
    0 / 50 (0.00%)
    2 / 47 (4.26%)
         occurrences all number
    0
    2
    Musculoskeletal chest pain
         subjects affected / exposed
    2 / 50 (4.00%)
    0 / 47 (0.00%)
         occurrences all number
    2
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    4 / 50 (8.00%)
    3 / 47 (6.38%)
         occurrences all number
    7
    3
    Influenza
         subjects affected / exposed
    3 / 50 (6.00%)
    1 / 47 (2.13%)
         occurrences all number
    3
    1
    Sinusitis
         subjects affected / exposed
    1 / 50 (2.00%)
    3 / 47 (6.38%)
         occurrences all number
    1
    3
    Bronchitis
         subjects affected / exposed
    2 / 50 (4.00%)
    1 / 47 (2.13%)
         occurrences all number
    2
    1
    Escherichia urinary tract infection
         subjects affected / exposed
    1 / 50 (2.00%)
    2 / 47 (4.26%)
         occurrences all number
    1
    3
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 50 (0.00%)
    3 / 47 (6.38%)
         occurrences all number
    0
    3
    Urinary tract infection
         subjects affected / exposed
    2 / 50 (4.00%)
    0 / 47 (0.00%)
         occurrences all number
    2
    0
    Conjunctivitis
         subjects affected / exposed
    2 / 50 (4.00%)
    0 / 47 (0.00%)
         occurrences all number
    2
    0
    Metabolism and nutrition disorders
    Type 2 diabetes mellitus
         subjects affected / exposed
    2 / 50 (4.00%)
    2 / 47 (4.26%)
         occurrences all number
    2
    2
    Dehydration
         subjects affected / exposed
    1 / 50 (2.00%)
    2 / 47 (4.26%)
         occurrences all number
    1
    2
    Hypertriglyceridaemia
         subjects affected / exposed
    1 / 50 (2.00%)
    2 / 47 (4.26%)
         occurrences all number
    1
    2

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 Jul 2009
    Extension of study completion date. Non-selection criteria: patients currently or having treated with not marketed (added) ivabradine. Time window between the last visit of double-blind treatment period and the visit of run-out period: 1 to 3 months allowed. Cyclosporine removed from unauthorised concomitant treatments.
    23 Dec 2009
    Extension of study completion date.
    27 Apr 2012
    Number of planned patients reduced from 300 to 100. Extension of study completion date.
    10 Sep 2012
    To comply with changes of the Summary of Products Characteristics for ivabradine product. Final threshold values for potential clinical concern related to the ERG responses were calculated taking in account the data of patients included in the study.

    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-Wed Apr 24 08:27:31 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA