NCT02441218

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
6,505

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Sep 2006

Typical duration for phase_3

Geographic Reach
2 countries

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2006

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2010

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2010

Completed
5.1 years until next milestone

First Submitted

Initial submission to the registry

May 5, 2015

Completed
7 days until next milestone

First Posted

Study publicly available on registry

May 12, 2015

Completed
2 months until next milestone

Results Posted

Study results publicly available

June 29, 2015

Completed
Last Updated

January 3, 2020

Status Verified

January 1, 2020

Enrollment Period

3.6 years

First QC Date

May 5, 2015

Results QC Date

May 12, 2015

Last Update Submit

January 2, 2020

Conditions

Chronic Heart Failure

Outcome Measures

Primary Outcomes (1)

  • 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.

    All over the study (up to 42 months).

Secondary Outcomes (9)

  • Cardiovascular Death

    From the date of randomization until the date of death, up to 42 months

  • Hospitalisation for Worsening Heart Failure

    From the date of randomization to the date of first documented hospitalisation, up to 42 months

  • All-cause Mortality

    From the date of randomisation to death, up to 42 months.

  • Death From Heart Failure

    From the date of randomisation to death, up to 42 months.

  • Hospitalisation for Any Cause

    From the date of randomisation to the date of first documented hospitalisation, up to 42 months

  • +4 more secondary outcomes

Study Arms (2)

Ivabradine

EXPERIMENTAL
Drug: Ivabradine

Placebo

PLACEBO COMPARATOR
Drug: Placebo

Interventions

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.

Ivabradine
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.

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Hôpital Pitié-Salpétrière

Paris, 75013, France

Location

Göteborg University

Gothenburg, S 41685, Sweden

Location

Related Publications (4)

  • 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.

    PMID: 20801500RESULT

  • 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.

    PMID: 20801495RESULT

  • 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.

    PMID: 32580655DERIVED

  • 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.

    PMID: 28205056DERIVED

MeSH Terms

Interventions

Ivabradine

Intervention Hierarchy (Ancestors)

BenzazepinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Limitations and Caveats

The section Other Adverse Events (Not including serious) has been completed by the sponsor to include only the Non Serious Adverse Events emergent on treatment during the study.

Results Point of Contact

Title
Therapeutic Innovation Pole
Organization
Institut de Recherches Internationales Servier (I.R.I.S.)
clinicaltrials@servier.com
+33155724366

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 5, 2015

First Posted

May 12, 2015

Study Start

September 1, 2006

Primary Completion

April 1, 2010

Study Completion

April 1, 2010

Last Updated

January 3, 2020

Results First Posted

June 29, 2015

Record last verified: 2020-01

Data Sharing

IPD Sharing
Will share

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.

Shared Documents
STUDY PROTOCOL, SAP, ICF, CSR
Time Frame
After Marketing Authorisation in EEA or US if the study is used for the approval.
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.
More information

Locations

SE(1)FR(1)