Trial record 19 of 825 for:    Open Studies | "Heart Failure"

If Channel Blockade With Ivabradine in Patients With Diastolic Heart Failure

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2008 by St Vincent's University Hospital, Ireland.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
St Vincent's University Hospital, Ireland
ClinicalTrials.gov Identifier:
NCT00757055
First received: September 19, 2008
Last updated: NA
Last verified: September 2008
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Diastolic Heart Failure
Drug: Ivabradine
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: If Channel Blockade With Ivabradine in Patients With Diastolic Heart Failure

Resource links provided by NLM:


Further study details as provided by St Vincent's University Hospital, Ireland:

Primary Outcome Measures:
  • Improvement in echocardiographic indices of diastolic dysfunction [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Improvement in 6 minute walk test [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Patient global assessment [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 10
Study Start Date: September 2008
Estimated Study Completion Date: April 2009
Estimated Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Patients on ivabradine titrated to heart rate
Drug: Ivabradine
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.
Other Name: Procoralen is brand name for Ivabradine
Placebo Comparator: 2
No therapy given
Drug: Placebo
No active treatment given

Detailed Description:

Background:

Almost half of all patients with heart failure (HF) have preserved systolic function (PSHF) or heart failure with normal ejection fraction (HFNEF). Some of these have valvular abnormalities such as severe mitral or aortic regurgitation, severe anaemia, thyrotoxicosis or rarer tropical causes for heart failure. However, the majority of those with PSHF often have echocardiographic evidence of impaired diastolic function i.e. impaired relaxation and increased stiffness. This diastolic dysfunction may be related to age, hypertension or ischaemia. There is little evidence for any effective therapy in this large HF population despite randomised trials comparing placebo to ACE inhibitors i.e. perindopril in PEP-HF or angiotensin receptor blockers i.e. candesartan in the CHARM Preserved trial. There are also ongoing studies of aldosterone antagonists in diastolic heart failure i.e. eplerenone vs placebo in TOPCAT which continues to recruit.

In the absence of a strong evidence base, many physicians treat these patients with drugs that slow the heart rate, namely the calcium channel blocker verapamil and beta blockers. This has the effect of prolonging diastole or filling time and theoretically improving stroke volume thus reducing left ventricular end diastolic pressures (LVEDP) with resultant drop in wall stress and therefore less stimulus for myocardial fibrosis which exacerbates diastolic dysfunction by impeding compliance.

Hypothesis:

An alternative mechanism for slowing the heart rate is with ivabradine, a novel If channel blocker which acts purely on the sino atrial node with a mean heart rate lowering of 10 bpm in angina patients. This may result in improved diastolic filling which could be demonstrate by echocardiography, lower pulmonary capillary wedge pressures, which could be determined by measuring the E:E' ratio using tissue Doppler techniques, improving effort tolerance, estimated by assessing change in distance walked over 6 minutes and both a physician assessment using NYHA score as well as a patient Global Assessment and possibly better quality of life, determined by the Minnesota Living with Heart Failure Questionnaires.

Other theoretical improvements could be in the degree of stiffness or fibrosis due to reduced LV wall stress secondary to the longer filling time. This could be assessed using surrogates of wall strain such as brain natruretic peptide (BNP), wall stress as measured by strain rate imaging on echocardiography.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00757055

Contacts
Contact: Dermot J McCaffrey, MB MRCP FRACP 35312304629 dermotmccaffrey@gmail.com
Contact: Ken McDonald, MB MD FRCPI 35312304629 ken@heartbeat-trust.org

Locations
Ireland
Heart Failure Unit, St Michaels Hospital Recruiting
Dublin, Ireland
Sponsors and Collaborators
St Vincent's University Hospital, Ireland
Investigators
Principal Investigator: Dermot J McCaffrey, MB MRCPI FRACP St Vincents University Hospital, Elm Park Dublin 4 Ireland
  More Information

No publications provided

Responsible Party: Dr Dermot McCaffrey, St Vincent's University Hospital, Ireland
ClinicalTrials.gov Identifier: NCT00757055     History of Changes
Other Study ID Numbers: N2008/Iva/DD
Study First Received: September 19, 2008
Last Updated: September 19, 2008
Health Authority: Ireland: Irish Medicines Board

Keywords provided by St Vincent's University Hospital, Ireland:
Heart failure
Diastolic heart failure
Heart failure with preserved systolic function
Heart failure with normal ejection fraction
Ivabradine
Diastolic dysfunction

Additional relevant MeSH terms:
Heart Failure
Heart Failure, Diastolic
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on September 16, 2014