If Channel Blockade With Ivabradine in Patients With Diastolic Heart Failure

NCT00757055 | Withdrawn Phase 2

• 1 other identifier: N2008/Iva/DD
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate whether the medicine ivabradine, a novel drug which slows the heart rate has a favourable effect on patients with diastolic heart failure. Ivabradine is a specific heart rate-lowering agent. It has a licence for treating patients with angina who are intolerant of agents such as beta blockers or whose angina is not adequately controlled. It has been shown to prolong exercise tolerance in these patients and to reduce the frequency of chest pain. Its mechanism of action is felt to be purely due to reducing heart rate, by as much as 10 beats per minute at rest, as well as by reducing the heart rate response to exercise. Patients with diastolic heart failure often complain of breathlessness on exertion which relates to the stiffness or lack of compliance of their heart i.e. the heart fails to relax rapidly enough to allow it to fill with blood between each heart beat. This may result in high pressure in the heart chamber which backs up in to the lungs and may be experienced as breathlessness. There is little evidence that any specific therapy benefits patients with this type of heart failure besides treating coexisting problems such as high blood pressure or angina. By slowing the heart rate down with ivabradine, the heart would have a longer time to fill during exercise which would make it more effective. This slowing of the heart rate may therefore relieve the breathlessness experienced on activity such as walking to the shops or up a flight of stairs etc.

Conditions

Diastolic Heart Failure

Keywords

Heart failure; Diastolic heart failure; Heart failure with preserved systolic function; Heart failure with normal ejection fraction; Ivabradine; Diastolic dysfunction

Outcome Measures

Primary Outcomes (1)

• Improvement in echocardiographic indices of diastolic dysfunction

  12 weeks

Secondary Outcomes (2)

• Improvement in 6 minute walk test

  12 weeks

• Patient global assessment

  12 weeks

Study Arms (2)

1

ACTIVE COMPARATOR

Patients on ivabradine titrated to heart rate

Drug: Ivabradine

2

PLACEBO COMPARATOR

No therapy given

Drug: Placebo

Interventions

Ivabradine DRUG

Ivabradine titrated to heart rate starting at 5 mg bd and increasing to maximum of 7.5 mg bd or reducing to 2.5 mg if heart rate \< 60 bpm.

Also known as: Procoralen is brand name for Ivabradine

1

Placebo DRUG

No active treatment given

2

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients must have a clinical diagnosis of diastolic heart failure as defined by all 3 of the following criteria:
• Presence of clinical heart failure for greater than or equal to 3 months before the screening visit. At the time of enrollment they should be in NYHA functional class I-III heart failure
• Left ventricular ejection fraction (LVEF) of greater than or equal to 50% (by echo or ventriculography) within 3 months of screening and LVEF still greater than or equal to 50% on day of enrollment
• BNP (b-type natruretic peptide) greater than or equal to 200 pg/ml at time of heart failure diagnosis
• Patients must be euvolaemic on clinical examination and have been clinically stable for at least 4 weeks with no medication changes
• Systolic blood pressure less than or equal to 150 mmHg but \> 85 mmHg and diastolic blood pressure less than or equal to 95 mmHg for 4 weeks prior to and at the time of enrollment
• Able to walk at least 50 meters at time of enrollment

You may not qualify if:

• Aged \< 18 or \> 85
• Primary hemodynamically significant uncorrected valvular heart disease, obstructive or regurgitant
• Any planned revascularisation i.e. CABG or stenting or performed within last 90 days
• Any myocardial infarct within last 90 days
• Significant chronic obstructive airways disease in the opinion of the investigator
• Known infiltrative or hypertrophic obstructive cardiomyopathy or known pericardial constriction
• Inability to sign informed consent
• Atrial fibrillation
• Heart transplant recipient
• Currently implanted left ventricular assist device
• Stroke in past 90 days
• Gastrointestinal disorder that could interfere with study drug absorption
• Known intolerance to ivabradine
• Current participation (including prior 30 days) in any other therapeutic trial
• Any condition that, in the opinion of the investigator, may prevent the participant from adhering to the trial protocol

Sponsors & Collaborators

• St Vincent's University Hospital, Ireland: lead

Study Sites (1)

Heart Failure Unit, St Michaels Hospital

Dublin, Ireland

Location

MeSH Terms

Conditions

Heart Failure, Diastolic; Heart Failure

Interventions

Ivabradine

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Dermot J McCaffrey, MB MRCPI FRACP

  St Vincents University Hospital, Elm Park Dublin 4 Ireland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: September 19, 2008
• First Posted: September 22, 2008
• Study Start: December 1, 2012
• Primary Completion: November 1, 2013
• Study Completion: January 1, 2014
• Last Updated: November 25, 2014

Record last verified: 2014-11

Locations

IE (1)