Clinical trial NCT02441218: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Heart Failure
Lead sponsor: Servier
Sponsor class: INDUSTRY
First posted: 2015-05-12
Enrollment: 6505
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Primary Composite Endpoint: First Event Among Cardiovascular Death (Including Death of Unknown Cause) or Hospitalization for Worsening Heart Failure.
timeFrame: All over the study (up to 42 months).
Secondary outcomes:
measure: Cardiovascular Death
timeFrame: From the date of randomization until the date of death, up to 42 months
measure: Hospitalisation for Worsening Heart Failure
timeFrame: From the date of randomization to the date of first documented hospitalisation, up to 42 months
measure: All-cause Mortality
timeFrame: From the date of randomisation to death, up to 42 months.
measure: Death From Heart Failure
timeFrame: From the date of randomisation to death, up to 42 months.
measure: Hospitalisation for Any Cause
timeFrame: From the date of randomisation to the date of first documented hospitalisation, up to 42 months
measure: Hospitalisation for Cardiovascular Reason
timeFrame: From the date of randomisation to the first documented hospitalisation, up to 42 months
measure: Unplanned Hospitalisation for Any Cause
timeFrame: From the date of randomisation to the first documented hospitalisation, up to 42 months
measure: Unplanned Hospitalisation for CV Reason
timeFrame: From the date of randomisation to the first documented hospitalisation, up to 42 months.
measure: Secondary Composite Endpoint
timeFrame: From the date of randomisation to the date of the first event, up to 42 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Pitié-Salpétrière
city: Göteborg
country: Sweden
facility: Göteborg University
Study officials:
References:
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.
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.
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.
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.