Coronary Artery DiseasePhase 3SIGNIFYNCT02446990
Effects of Ivabradine in Patients With Stable Coronary Artery Disease Without Clinical Heart Failure
A Phase 3 study testing Ivabradine in people with Coronary Artery Disease, run by Institut de Recherches Internationales Servier at 2 sites in 2 countries.
Trial summary
The purpose of this study is to evaluate the effect of ivabradine on cardiovascular events in patients with coronary artery disease. Read more about this study
- Who is it for?
- Ages 55 years and older
- Conditions the study is for
- Coronary Artery Disease
- What is being tested?
- Ivabradine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 19,102 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Sep 2009to Jan 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Evidence of coronary artery disease
- Sinus rhythm and resting heart rate equal or higher than 70 bpm
Who cannot join
- Unstable cardiovascular condition
- Known hypersensitivity to ivabradine or current treatment with marketed ivabradine
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
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
The purpose of this study is to evaluate the effect of ivabradine on cardiovascular events in patients with coronary artery disease.
- Conditions
- Coronary Artery Disease
- Being tested
- Ivabradine, Placebo
- Medical subject headings
- Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IvabradineDrug
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Ivabradine | Experimental | Not described Receives: Drug: Ivabradine |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Composite Endpoint
First event among cardiovascular death or non-fatal myocardial infarction
Measured: 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 outcomes (13)
All-cause Mortality
Measured: From the date of randomisation to death, up to 48 months
Cardiovascular Mortality
Component of the primary composite endpoint
Measured: From the date of randomisation to death, up to 48 months
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
Measured: From the date of randomisation to death, up to 48 months
Fatal Myocardial Infarction
Non-composite secondary endpoint
Measured: From the date of randomisation to death, up to 48 months
Non-fatal Myocardial Infarction
Component of the primary composite endpoint
Measured: From the date of randomisation to the date of first occurrence of the event, up to 48 months
Elective Coronary Revascularisation
Non-composite secondary endpoint
Measured: From the date of randomisation to the date of first occurrence of the event, up to 48 months
Coronary Revascularisation (Elective or Not)
Non-composite secondary endpoint
Measured: From the date of randomisation to the date of first occurrence of the event, up to 48 months
Secondary Composite Endpoint
Fatal or non-fatal myocardial infarction
Measured: From the date of randomisation to the date of first occurrence of the event, up to 48 months
Secondary Composite Endpoint
Fatal or non-fatal myocardial infarction, coronary revascularisation
Measured: From the date of randomisation to the date of first occurrence of the event, up to 48 months
Secondary Composite Endpoint
Fatal or non-fatal myocardial infarction, coronary revascularisation, unstable angina
Measured: From the date of randomisation to the date of first occurrence of the event, up to 48 months
Secondary Composite Endpoint
Cardiovascular death, non-fatal myocardial infarction, non-fatal stroke
Measured: From the date of randomisation to the date of first occurrence of the event, up to 48 months
Secondary Composite Endpoint
Coronary death, non-fatal myocardial infarction
Measured: From the date of randomisation to the date of first occurrence of the event, up to 48 months
Secondary Composite Endpoint
Non-fatal myocardial infarction, coronary revascularisation, unstable angina
Measured: From the date of randomisation to the date of first occurrence of the event, up to 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2015 (estimated)
- Study startSep 2009
- Primary completionJan 2014
- Study completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 19,102 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut de Recherches Internationales Servier
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02446990
- Sponsor's protocol ID
- CL3-16257-083
- Other IDs
- 2009-011360-10, 2009
- Acronym
- SIGNIFY
- Status last verified
- Jul 2024
- First submitted
- 5 May 2015
- Last updated
- 26 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 25176136Fox 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.
PubMed 24093844
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02446990
- Acronym / sponsor ID
- SIGNIFY / CL3-16257-083
- Conditions
- Coronary Artery Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19,102 participants (actual)
- Lead sponsor
- Institut de Recherches Internationales ServierUniversity, hospital or other
- Study start
- Sep 2009
- Primary completion
- Jan 2014 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 18 May 2015 (estimated)
- Results
- Posted 25 Jun 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the effect of ivabradine on cardiovascular events in patients with coronary artery disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ivabradine | Experimental | Drug: Ivabradine |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 55 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Evidence of coronary artery disease
- Sinus rhythm and resting heart rate equal or higher than 70 bpm
Key exclusion criteria (2 listed)
- Unstable cardiovascular condition
- Known hypersensitivity to ivabradine or current treatment with marketed ivabradine
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ivabradine5 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. | Drug | Ivabradine |
| PlaceboMatching 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. | Drug | Placebo |
Primary outcome
Primary Composite Endpoint
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.
First event among cardiovascular death or non-fatal myocardial infarction
13 secondary outcomes
All-cause Mortality
Time frame: From the date of randomisation to death, up to 48 months
Cardiovascular Mortality
Time frame: From the date of randomisation to death, up to 48 months
Coronary Mortality
Time frame: From the date of randomisation to death, up to 48 months
Fatal Myocardial Infarction
Time frame: From the date of randomisation to death, up to 48 months
Non-fatal Myocardial Infarction
Time frame: From the date of randomisation to the date of first occurrence of the event, up to 48 months
Elective Coronary Revascularisation
Time frame: From the date of randomisation to the date of first occurrence of the event, up to 48 months
Coronary Revascularisation (Elective or Not)
Time frame: From the date of randomisation to the date of first occurrence of the event, up to 48 months
Secondary Composite Endpoint
Time frame: From the date of randomisation to the date of first occurrence of the event, up to 48 months
Secondary Composite Endpoint
Time frame: From the date of randomisation to the date of first occurrence of the event, up to 48 months
Secondary Composite Endpoint
Time frame: From the date of randomisation to the date of first occurrence of the event, up to 48 months
Secondary Composite Endpoint
Time frame: From the date of randomisation to the date of first occurrence of the event, up to 48 months
Secondary Composite Endpoint
Time frame: From the date of randomisation to the date of first occurrence of the event, up to 48 months
Secondary Composite Endpoint
Time frame: From the date of randomisation to the date of first occurrence of the event, up to 48 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 25176136Fox 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 publication: PubMed 24093844Fox 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.
- Individual participant dataSharing planned: Yes. 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.
Related trials for Coronary Artery Disease
Not yet recruiting
Effect of Stress Ball Use During Femoral Arterial Sheath Removal After Coronary Angiography
Femoral Arterial Sheath Removal, Stress Ball
Active, not recruiting
Shockwave™ vs Surgical Endarterectomy for Calcified Severe Common Femoral Artery Stenosis: Comparison of Efficacy, Safety and Long-Term Outcomes
Common Femoral Artery Stenosis, Calcification; Heart
Not yet recruitingPhase 4
Roxadustat and Myocardial Injury After Off-Pump Coronary Artery Bypass Surgery
Coronary Artery Disease, Coronary Artery Bypass Grafting
RecruitingObservational study
Preoperative Gastric Ultrasound and Left Ventricular Function in Coronary Artery Bypass Surgery
Coronary Artery Disease, Left Ventricular Systolic Dysfunction
Active, not recruiting
The OCTOBER Trial - European Trial on Optical Coherence Tomography Optimized Bifurcation Event Reduction (OCTOBER)
Ischaemic Heart Disease, Ischemic Heart Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ivabradine in people with Coronary Artery Disease, run by Institut de Recherches Internationales Servier at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Jun 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Composite Endpoint (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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02446990, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2024.