Clinical Trial Results:
Effects of oral administration of ivabradine (7.5 mg bid) on post-ischaemic stunning induced by exercise stress in patients with coronary artery disease and exercise inducible ischaemia.
Summary
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EudraCT number |
2011-000783-98 |
Trial protocol |
IT |
Global end of trial date |
13 Aug 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Jul 2016
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First version publication date |
06 Aug 2015
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CL2-16257-095
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Additional study identifiers
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ISRCTN number |
ISRCTN90566768 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Institut de Recherches Internationales Servier
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Sponsor organisation address |
50 rue Carnot, Suresnes, France, 92284
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Public contact |
Innovation Therapeutic Pole, Institut de Recherches Internationales Servier, +33 155724366, clinicaltrials@servier.com
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Scientific contact |
Innovation Therapeutic Pole, Institut de Recherches Internationales Servier, +33 155724366, clinicaltrials@servier.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
13 Aug 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
13 Aug 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
13 Aug 2014
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess the effects of Ivabradine on post-ischaemic stunning induced by exercise stress in patients with stable coronary artery disease and exercise-inducible ischaemia
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Protection of trial subjects |
The study treatment could be prematurely discontinued if it was not tolerated, no longer appropriate or considered as contra-indicated.
For the sake of safety, only patients presenting with a positive exercise at moderate or high workload were selected in the study, thus patients with low-effort inducible ischemia were not included.
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Background therapy |
Previous cardiovascular medication were maintained except previous anti-angina treatments. Short acting nitrates were authorized during the study. | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
27 Mar 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Italy: 15
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Worldwide total number of subjects |
15
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EEA total number of subjects |
15
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
5
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From 65 to 84 years |
10
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was carried out under the supervision of Prof. P.G. Camici in a unique centre at Istituto Scientifico Universitario San Raffaele, Milan, Italy | ||||||
Pre-assignment
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Screening details |
Study population was male and female patients with proven Coronary Artery Disease, Left Ventricular Ejection Fraction ≥ 40%, sinus rhythm, resting heart rate ≥ 70 bpm and exercise-inducible myocardial ischaemia at moderate to high workload and subsequent stunning. 26 patients were screened; 25 patients pre-selected and 15 patients were included. | ||||||
Pre-assignment period milestones
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Number of subjects started |
26 [1] | ||||||
Number of subjects completed |
15 | ||||||
Pre-assignment subject non-completion reasons
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Reason: Number of subjects |
non compliance to selection criteria: 11 | ||||||
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: 11 patients showed non-compliance to selection criteria |
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Period 1
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Period 1 title |
Ivabradine (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
Arms
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Arm title
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ivabradine | ||||||
Arm description |
ivabradine 7.5 mg | ||||||
Arm type |
test drug | ||||||
Investigational medicinal product name |
ivabradine 7.5 mg
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
1 tablet twice daily during meals
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Baseline characteristics reporting groups
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Reporting group title |
Ivabradine
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
ivabradine
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Reporting group description |
ivabradine 7.5 mg | ||
Subject analysis set title |
Included Set
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
All included patients
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Subject analysis set title |
Full Analysis Set
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All included patients having received at least one study drug intake and having a strain value at baseline and at W2 visit, at each time point (at rest, at peak and at 3 minutes of recovery) for at least one segment showing exercise-inducible myocardial stunning at baseline.
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Subject analysis set title |
Safety Set
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All included patients having received at least one study drug intake.
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End point title |
Post-ischaemic myocardial stunning [1] | ||||||||||||||||
End point description |
By using bi-dimensional echocardiography at rest and at peak of exercise and during the recovery phase, a strain value (%) was measured for 16 segments of the LV myocardial wall. The segments showing post-ischaemic myocardial stunning at baseline were assessed for efficacy results.
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End point type |
Primary
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End point timeframe |
The primary endpoint was the post-ischaemic myocardial stunning evaluating changes (%) in regional myocardial wall motion from rest to peak exercise and to recovery time points (3 min, 10 min, 20 min). Change from baseline to W2 was provided.
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: only descriptive analyses were done |
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No statistical analyses for this end point |
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Adverse events information [1]
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Timeframe for reporting adverse events |
All over the study
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Assessment type |
Systematic | ||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||
Dictionary version |
17.0
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Reporting groups
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Reporting group title |
ivabradine
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Reporting group description |
- | ||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||
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Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Low number of patients receiving the study drug and short duration of the treatment period. |
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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03 Oct 2012 |
To extend the enrolment period by one year from October 2012 to October 2013.
To update information on concomitant treatments and the list of adverse events for which specific information was requested and already collected, if any. |
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11 Jul 2013 |
To extent the enrolment period by ten months from October 2013 to August 2014
To clarify a study procedure regarding the blood sampling results to be checked by the investigator before the inclusion of the patient |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |