Chronic Heart FailurePhase 3SHIFTNCT02441218
Effects of Ivabradine on Cardiovascular Events in Patients With Moderate to Severe Chronic Heart Failure and Left Ventricular Systolic Dysfunction. A Three-year International Multicentre Study
A Phase 3 study testing Ivabradine in people with Chronic Heart Failure, run by Institut de Recherches Internationales Servier at 2 sites in 2 countries.
Trial summary
The primary objective of this study is to demonstrate the superiority of ivabradine over placebo in the reduction of cardiovascular mortality or hospitalisation for worsening heart failure in patients with moderate to severe symptoms of chronic heart failure, a reduced left ventricular ejection fraction and currently… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Heart Failure
- 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
- 6,505 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Sep 2006to Apr 2010
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Symptomatic Chronic heart failure (NYHA II, III or IV)
- Left ventricular systolic dysfunction (LVEF ≤ 35%)
- Sinus rhythm and resting heart rate ≥ 70 bpm
- Optimal and unchanged CHF medications or dosages
Who cannot join
- Unstable condition within previous 4 weeks
- Myocardial infarction or coronary revascularisation within previous 2 months
- Stroke or transient cerebral ischaemia within previous 4 weeks
- Congenital heart disease
- Severe valvular disease
- Active myocarditis
- Permanent atrial fibrillation or flutter
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
The primary objective of this study is to demonstrate the superiority of ivabradine over placebo in the reduction of cardiovascular mortality or hospitalisation for worsening heart failure in patients with moderate to severe symptoms of chronic heart failure, a reduced left ventricular ejection fraction and currently receiving recommended therapy for this disease.
- Conditions
- Chronic Heart Failure
- Being tested
- Ivabradine, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IvabradineDrug
2.5mg, 5mg or 7.5mg tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 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 42 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 (Including Death of Unknown Cause) or Hospitalization for Worsening Heart Failure.
Number of patients having experienced the Primary Composite Endpoint.
Measured: All over the study (up to 42 months).
Secondary outcomes (9)
Cardiovascular Death
Component of the primary composite endpoint
Measured: From the date of randomization until the date of death, up to 42 months
Hospitalisation for Worsening Heart Failure
Measured: From the date of randomization to the date of first documented hospitalisation, up to 42 months
All-cause Mortality
Measured: From the date of randomisation to death, up to 42 months.
Death From Heart Failure
Component of cardiovascular death
Measured: From the date of randomisation to death, up to 42 months.
Hospitalisation for Any Cause
Measured: From the date of randomisation to the date of first documented hospitalisation, up to 42 months
Hospitalisation for Cardiovascular Reason
Measured: From the date of randomisation to the first documented hospitalisation, up to 42 months
Unplanned Hospitalisation for Any Cause
Measured: From the date of randomisation to the first documented hospitalisation, up to 42 months
Unplanned Hospitalisation for CV Reason
Measured: From the date of randomisation to the first documented hospitalisation, up to 42 months.
Secondary Composite Endpoint
CV death, hospitalisation for worsening HF or hospitalisation for non-fatal myocardial infarction
Measured: From the date of randomisation to the date of the first event, up to 42 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2015 (estimated)
- Study startSep 2006
- Primary completionApr 2010
- Study completionApr 2010
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 (4)Papers the sponsor has linked to this study.
- Other trials for Chronic Heart FailureStudies 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
- 6,505 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
- NCT02441218
- Sponsor's protocol ID
- CL3-16257-063
- Other IDs
- 2006-000708-18
- Acronym
- SHIFT
- Status last verified
- Jan 2020
- First submitted
- 5 May 2015
- Last updated
- 3 Jan 2020
- 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
Swedberg K, Komajda M, Bohm M, Borer JS, Ford I, Dubost-Brama A, Lerebours G, Tavazzi L; SHIFT Investigators. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010 Sep 11;376(9744):875-85. doi: 10.1016/S0140-6736(10)61198-1.
PubMed 20801500Bohm M, Swedberg K, Komajda M, Borer JS, Ford I, Dubost-Brama A, Lerebours G, Tavazzi L; SHIFT Investigators. Heart rate as a risk factor in chronic heart failure (SHIFT): the association between heart rate and outcomes in a randomised placebo-controlled trial. Lancet. 2010 Sep 11;376(9744):886-94. doi: 10.1016/S0140-6736(10)61259-7.
PubMed 20801495Tyl B, Lopez Sendon J, Borer JS, Lopez De Sa E, Lerebours G, Varin C, De Montigny A, Pannaux M, Komajda M. Comparison of Outcome Adjudication by Investigators and by a Central End Point Committee in Heart Failure Trials: Experience of the SHIFT Heart Failure Study. Circ Heart Fail. 2020 Jul;13(7):e006720. doi: 10.1161/CIRCHEARTFAILURE.119.006720. Epub 2020 Jun 25.
PubMed 32580655Griffiths A, Paracha N, Davies A, Branscombe N, Cowie MR, Sculpher M. Analyzing Health-Related Quality of Life Data to Estimate Parameters for Cost-Effectiveness Models: An Example Using Longitudinal EQ-5D Data from the SHIFT Randomized Controlled Trial. Adv Ther. 2017 Mar;34(3):753-764. doi: 10.1007/s12325-016-0471-x. Epub 2017 Feb 15.
PubMed 28205056
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Ivabradine on Cardiovascular Events in Patients With Moderate to Severe Chronic Heart Failure and Left Ventricular Systolic Dysfunction. A Three-year International Multicentre Study
- ClinicalTrials.gov ID
- NCT02441218
- Acronym / sponsor ID
- SHIFT / CL3-16257-063
- Conditions
- Chronic Heart Failure
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6,505 participants (actual)
- Lead sponsor
- Institut de Recherches Internationales ServierUniversity, hospital or other
- Study start
- Sep 2006
- Primary completion
- Apr 2010 (actual)
- Study completion
- Apr 2010 (actual)
- First posted
- 12 May 2015 (estimated)
- Results
- Posted 29 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 primary objective of this study is to demonstrate the superiority of ivabradine over placebo in the reduction of cardiovascular mortality or hospitalisation for worsening heart failure in patients with moderate to severe symptoms of chronic heart failure, a reduced left ventricular ejection fraction and currently receiving recommended therapy for this 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
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Symptomatic Chronic heart failure (NYHA II, III or IV)
- Left ventricular systolic dysfunction (LVEF ≤ 35%)
- Sinus rhythm and resting heart rate ≥ 70 bpm
- Optimal and unchanged CHF medications or dosages
Key exclusion criteria (7 listed)
- Unstable condition within previous 4 weeks
- Myocardial infarction or coronary revascularisation within previous 2 months
- Stroke or transient cerebral ischaemia within previous 4 weeks
- Congenital heart disease
- Severe valvular disease
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 |
|---|---|---|
| Ivabradine2.5mg, 5mg or 7.5mg tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 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 42 months. | Drug | Placebo |
Primary outcome
Primary Composite Endpoint: First Event Among Cardiovascular Death (Including Death of Unknown Cause) or Hospitalization for Worsening Heart Failure.
Time frame: All over the study (up to 42 months).
Number of patients having experienced the Primary Composite Endpoint.
9 secondary outcomes
Cardiovascular Death
Time frame: From the date of randomization until the date of death, up to 42 months
Hospitalisation for Worsening Heart Failure
Time frame: From the date of randomization to the date of first documented hospitalisation, up to 42 months
All-cause Mortality
Time frame: From the date of randomisation to death, up to 42 months.
Death From Heart Failure
Time frame: From the date of randomisation to death, up to 42 months.
Hospitalisation for Any Cause
Time frame: From the date of randomisation to the date of first documented hospitalisation, up to 42 months
Hospitalisation for Cardiovascular Reason
Time frame: From the date of randomisation to the first documented hospitalisation, up to 42 months
Unplanned Hospitalisation for Any Cause
Time frame: From the date of randomisation to the first documented hospitalisation, up to 42 months
Unplanned Hospitalisation for CV Reason
Time frame: From the date of randomisation to the first documented hospitalisation, up to 42 months.
Secondary Composite Endpoint
Time frame: From the date of randomisation to the date of the first event, up to 42 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20801500Swedberg K, Komajda M, Bohm M, Borer JS, Ford I, Dubost-Brama A, Lerebours G, Tavazzi L; SHIFT Investigators. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010 Sep 11;376(9744):875-85. doi: 10.1016/S0140-6736(10)61198-1.
- Results publication: PubMed 20801495Bohm M, Swedberg K, Komajda M, Borer JS, Ford I, Dubost-Brama A, Lerebours G, Tavazzi L; SHIFT Investigators. Heart rate as a risk factor in chronic heart failure (SHIFT): the association between heart rate and outcomes in a randomised placebo-controlled trial. Lancet. 2010 Sep 11;376(9744):886-94. doi: 10.1016/S0140-6736(10)61259-7.
- Derived from this study: PubMed 32580655Tyl B, Lopez Sendon J, Borer JS, Lopez De Sa E, Lerebours G, Varin C, De Montigny A, Pannaux M, Komajda M. Comparison of Outcome Adjudication by Investigators and by a Central End Point Committee in Heart Failure Trials: Experience of the SHIFT Heart Failure Study. Circ Heart Fail. 2020 Jul;13(7):e006720. doi: 10.1161/CIRCHEARTFAILURE.119.006720. Epub 2020 Jun 25.
- Derived from this study: PubMed 28205056Griffiths A, Paracha N, Davies A, Branscombe N, Cowie MR, Sculpher M. Analyzing Health-Related Quality of Life Data to Estimate Parameters for Cost-Effectiveness Models: An Example Using Longitudinal EQ-5D Data from the SHIFT Randomized Controlled Trial. Adv Ther. 2017 Mar;34(3):753-764. doi: 10.1007/s12325-016-0471-x. Epub 2017 Feb 15.
- 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.
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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 Chronic Heart Failure, 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 4 inclusion and 7 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 3 Jan 2020. 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 France, Sweden. 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 29 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: First Event Among Cardiovascular Death (Including Death of Unknown Cause) or Hospitalization for Worsening Heart Failure. (time frame: All over the study (up to 42 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 NCT02441218, which also lists 4 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 3 Jan 2020.