Effects of Ivabradine in Patients With Stable Coronary Artery Disease Without Clinical Heart Failure (SIGNIFY)
Primary Purpose
Coronary Artery Disease
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Ivabradine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Coronary Artery Disease
Eligibility Criteria
Inclusion Criteria:
- Evidence of coronary artery disease
- Sinus rhythm and resting heart rate equal or higher than 70 bpm
Exclusion Criteria:
- Unstable cardiovascular condition
- Known hypersensitivity to ivabradine or current treatment with marketed ivabradine
Sites / Locations
- Azienda Ospedaliera Universitaria di Ferrara
- Royal Brompton Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Ivabradine
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Primary Composite Endpoint
First event among cardiovascular death or non-fatal myocardial infarction
Secondary Outcome Measures
All-cause Mortality
Cardiovascular Mortality
Component of the primary composite endpoint
Coronary Mortality
Coronary mortality including sudden death of unknown cause, death from myocardial infarction, death from heart failure, death from coronary artery procedure, presumed arrhythmic death
Fatal Myocardial Infarction
Non-composite secondary endpoint
Non-fatal Myocardial Infarction
Component of the primary composite endpoint
Elective Coronary Revascularisation
Non-composite secondary endpoint
Coronary Revascularisation (Elective or Not)
Non-composite secondary endpoint
Secondary Composite Endpoint
Fatal or non-fatal myocardial infarction
Secondary Composite Endpoint
Fatal or non-fatal myocardial infarction, coronary revascularisation
Secondary Composite Endpoint
Fatal or non-fatal myocardial infarction, coronary revascularisation, unstable angina
Secondary Composite Endpoint
Cardiovascular death, non-fatal myocardial infarction, non-fatal stroke
Secondary Composite Endpoint
Coronary death, non-fatal myocardial infarction
Secondary Composite Endpoint
Non-fatal myocardial infarction, coronary revascularisation, unstable angina
Full Information
NCT ID
NCT02446990
First Posted
May 5, 2015
Last Updated
March 2, 2020
Sponsor
Institut de Recherches Internationales Servier
1. Study Identification
Unique Protocol Identification Number
NCT02446990
Brief Title
Effects of Ivabradine in Patients With Stable Coronary Artery Disease Without Clinical Heart Failure
Acronym
SIGNIFY
Official Title
Effects of Ivabradine in Patients With Stable Coronary Artery Disease Without Clinical Heart Failure. A Randomised Double-blind Placebo-controlled International Multicenter Study. Study Assessing the Morbi-mortality Benefits of the If Inhibitor Ivabradine in Patients With Coronary Artery Disease
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
September 2009 (undefined)
Primary Completion Date
January 2014 (Actual)
Study Completion Date
January 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut de Recherches Internationales Servier
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the effect of ivabradine on cardiovascular events in patients with coronary artery disease.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
19102 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ivabradine
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Ivabradine
Intervention Description
5 mg, 7.5 mg or 10 mg tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 48 months.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 48 months.
Primary Outcome Measure Information:
Title
Primary Composite Endpoint
Description
First event among cardiovascular death or non-fatal myocardial infarction
Time Frame
The events are expressed as the time to occurrence of the first event, defined as the duration between the date of randomisation and the date of first occurrence of event, assessed up to 48 months.
Secondary Outcome Measure Information:
Title
All-cause Mortality
Time Frame
From the date of randomisation to death, up to 48 months
Title
Cardiovascular Mortality
Description
Component of the primary composite endpoint
Time Frame
From the date of randomisation to death, up to 48 months
Title
Coronary Mortality
Description
Coronary mortality including sudden death of unknown cause, death from myocardial infarction, death from heart failure, death from coronary artery procedure, presumed arrhythmic death
Time Frame
From the date of randomisation to death, up to 48 months
Title
Fatal Myocardial Infarction
Description
Non-composite secondary endpoint
Time Frame
From the date of randomisation to death, up to 48 months
Title
Non-fatal Myocardial Infarction
Description
Component of the primary composite endpoint
Time Frame
From the date of randomisation to the date of first occurrence of the event, up to 48 months
Title
Elective Coronary Revascularisation
Description
Non-composite secondary endpoint
Time Frame
From the date of randomisation to the date of first occurrence of the event, up to 48 months
Title
Coronary Revascularisation (Elective or Not)
Description
Non-composite secondary endpoint
Time Frame
From the date of randomisation to the date of first occurrence of the event, up to 48 months
Title
Secondary Composite Endpoint
Description
Fatal or non-fatal myocardial infarction
Time Frame
From the date of randomisation to the date of first occurrence of the event, up to 48 months
Title
Secondary Composite Endpoint
Description
Fatal or non-fatal myocardial infarction, coronary revascularisation
Time Frame
From the date of randomisation to the date of first occurrence of the event, up to 48 months
Title
Secondary Composite Endpoint
Description
Fatal or non-fatal myocardial infarction, coronary revascularisation, unstable angina
Time Frame
From the date of randomisation to the date of first occurrence of the event, up to 48 months
Title
Secondary Composite Endpoint
Description
Cardiovascular death, non-fatal myocardial infarction, non-fatal stroke
Time Frame
From the date of randomisation to the date of first occurrence of the event, up to 48 months
Title
Secondary Composite Endpoint
Description
Coronary death, non-fatal myocardial infarction
Time Frame
From the date of randomisation to the date of first occurrence of the event, up to 48 months
Title
Secondary Composite Endpoint
Description
Non-fatal myocardial infarction, coronary revascularisation, unstable angina
Time Frame
From the date of randomisation to the date of first occurrence of the event, up to 48 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Evidence of coronary artery disease
Sinus rhythm and resting heart rate equal or higher than 70 bpm
Exclusion Criteria:
Unstable cardiovascular condition
Known hypersensitivity to ivabradine or current treatment with marketed ivabradine
Facility Information:
Facility Name
Azienda Ospedaliera Universitaria di Ferrara
City
Ferrara
ZIP/Postal Code
44100
Country
Italy
Facility Name
Royal Brompton Hospital
City
London
ZIP/Postal Code
SW3 6NP
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Researchers can ask for a study protocol, patient-level and/or study-level clinical trial data including clinical study reports (CSRs).
They can ask all interventional clinical studies:
submitted for new medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
Where Servier or an affiliate are the Marketing Authorization Holders (MAH). The date of the first Marketing Authorization of the new medicine (or the new indication) in one of the EEA Member States will be considered within this scope.
IPD Sharing Time Frame
After Marketing Authorisation in EEA or US if the study is used for the approval.
IPD Sharing Access Criteria
Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
IPD Sharing URL
http://clinicaltrials.servier.com
Citations:
PubMed Identifier
25176136
Citation
Fox K, Ford I, Steg PG, Tardif JC, Tendera M, Ferrari R; SIGNIFY Investigators. Ivabradine in stable coronary artery disease without clinical heart failure. N Engl J Med. 2014 Sep 18;371(12):1091-9. doi: 10.1056/NEJMoa1406430. Epub 2014 Aug 31.
Results Reference
result
PubMed Identifier
24093844
Citation
Fox K, Ford I, Steg PG, Tardif JC, Tendera M, Ferrari R. Rationale, design, and baseline characteristics of the Study assessInG the morbidity-mortality beNefits of the If inhibitor ivabradine in patients with coronarY artery disease (SIGNIFY trial): a randomized, double-blind, placebo-controlled trial of ivabradine in patients with stable coronary artery disease without clinical heart failure. Am Heart J. 2013 Oct;166(4):654-661.e6. doi: 10.1016/j.ahj.2013.06.024. Epub 2013 Sep 17.
Results Reference
result
Links:
URL
http://clinicaltrials.servier.com/wp-content/uploads/CL3-16257-083_synopsis_report.pdf
Description
Results summary
Learn more about this trial
Effects of Ivabradine in Patients With Stable Coronary Artery Disease Without Clinical Heart Failure
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