Back to resultsEffects 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 (SHIFT)
Primary Purpose
Chronic Heart Failure
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 Chronic Heart Failure
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Sites / Locations
- Hôpital Pitié-Salpétrière
- Göteborg University
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 (Including Death of Unknown Cause) or Hospitalization for Worsening Heart Failure.
Number of patients having experienced the Primary Composite Endpoint.
Secondary Outcome Measures
Cardiovascular Death
Component of the primary composite endpoint
Hospitalisation for Worsening Heart Failure
All-cause Mortality
Death From Heart Failure
Component of cardiovascular death
Hospitalisation for Any Cause
Hospitalisation for Cardiovascular Reason
Unplanned Hospitalisation for Any Cause
Unplanned Hospitalisation for CV Reason
Secondary Composite Endpoint
CV death, hospitalisation for worsening HF or hospitalisation for non-fatal myocardial infarction
Full Information
NCT ID
NCT02441218
First Posted
May 5, 2015
Last Updated
January 2, 2020
Sponsor
Institut de Recherches Internationales Servier
1. Study Identification
Unique Protocol Identification Number
NCT02441218
Brief 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
Acronym
SHIFT
Study Type
Interventional
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
September 2006 (undefined)
Primary Completion Date
April 2010 (Actual)
Study Completion Date
April 2010 (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 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Heart Failure
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
6505 (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
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.
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 42 months.
Primary Outcome Measure Information:
Title
Primary Composite Endpoint: First Event Among Cardiovascular Death (Including Death of Unknown Cause) or Hospitalization for Worsening Heart Failure.
Description
Number of patients having experienced the Primary Composite Endpoint.
Time Frame
All over the study (up to 42 months).
Secondary Outcome Measure Information:
Title
Cardiovascular Death
Description
Component of the primary composite endpoint
Time Frame
From the date of randomization until the date of death, up to 42 months
Title
Hospitalisation for Worsening Heart Failure
Time Frame
From the date of randomization to the date of first documented hospitalisation, up to 42 months
Title
All-cause Mortality
Time Frame
From the date of randomisation to death, up to 42 months.
Title
Death From Heart Failure
Description
Component of cardiovascular death
Time Frame
From the date of randomisation to death, up to 42 months.
Title
Hospitalisation for Any Cause
Time Frame
From the date of randomisation to the date of first documented hospitalisation, up to 42 months
Title
Hospitalisation for Cardiovascular Reason
Time Frame
From the date of randomisation to the first documented hospitalisation, up to 42 months
Title
Unplanned Hospitalisation for Any Cause
Time Frame
From the date of randomisation to the first documented hospitalisation, up to 42 months
Title
Unplanned Hospitalisation for CV Reason
Time Frame
From the date of randomisation to the first documented hospitalisation, up to 42 months.
Title
Secondary Composite Endpoint
Description
CV death, hospitalisation for worsening HF or hospitalisation for non-fatal myocardial infarction
Time Frame
From the date of randomisation to the date of the first event, up to 42 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
Facility Information:
Facility Name
Hôpital Pitié-Salpétrière
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
Göteborg University
City
Göteborg
ZIP/Postal Code
S 41685
Country
Sweden
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
20801500
Citation
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. Erratum In: Lancet. 2010 Dec 11;376(9757):1988. Lajnscak, M [corrected to Lainscak, M]; Rabanedo, I Roldan [corrected to Rabadan, I Roldan]; Leva, M [corrected to Ieva, M].
Results Reference
result
PubMed Identifier
20801495
Citation
Bohm 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.
Results Reference
result
PubMed Identifier
32580655
Citation
Tyl 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.
Results Reference
derived
PubMed Identifier
28205056
Citation
Griffiths 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.
Results Reference
derived
Links:
URL
http://clinicaltrials.servier.com/wp-content/uploads/CL3-16257-063_synopsis_report.pdf
Description
Results summary
Learn more about this trial
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
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