Ivabradine in Stage D Heart Failure Patients on Chronic Inotropes

December 6, 2024 updated by: Stephen Gottlieb, University of Maryland, Baltimore

Ivabradine in Stage D Heart Failure Patients on Chronic Inotropes: A Pilot Study

Ivabradine, a selective inhibitor of the If current in the sinoatrial node, provides heart rate reduction and leads to a reduction in heart failure hospitalizations. For this reason, the American College of Cardiology (ACC) and the American Heart Association (AHA) guidelines provide a class IIa recommendation for ivabradine in stable heart failure patients with LVEF 35% and New York Heart Association (NYHA) class II-III symptoms who are on a beta blocker at maximum tolerated dose with a resting heart rate of 70 beats per minute or greater. While ivabradine leads to improvement in outcomes in stable NYHA class II-III chronic heart failure patients, its role in class IV, stage D heart failure, and cardiogenic shock is less clear.

Ivabradine's effect on acute cardiogenic shock has been evaluated by two recent studies. In the MODIFY trial, a randomized control study evaluating ivabradine in patients with multiorgan dysfunction, the addition of ivabradine did not result in significant heart rate reductions or other positive clinical outcomes. However, a small prospective trial demonstrated a significant decrease in heart rate and NT-proBNP with the addition of ivabradine in patients with acute cardiogenic shock on dobutamine. While few data investigate ivabradine's role in acute cardiogenic shock, it has yet to be studied in heart failure patients on long-term inotropic therapy. Inotropes such as dobutamine and milrinone result in tachycardia and may lead to ventricular arrhythmias. Moreover, patients on chronic inotropes are typically off beta blockers and have few pharmacological options available to help reduce heart rates. Ivabradine may have a role in decreasing heart rate and improving outcomes in patients on chronic inotropes.

Given the benefits of ivabradine in stable chronic heart failure patients, we plan to perform a study investigating the role of ivabradine in NYHA Stage D patients on home inotropes.

Our primary objective is to analyze changes in two cardiac biomarkers, NT-proBNP and high-sensitivity troponin. Our secondary outcomes include changes in noninvasive echocardiographic hemodynamics, changes in arrhythmia burden, and heart failure symptom modification based on 6-minute walk test results.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Study Type

Interventional

Phase

  • Phase 4

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • NYHA Stage D heart failure on 2 weeks of consecutive IV dobutamine or milrinone
  • Followed at UMMC outpatient heart failure clinic or admitted to advanced heart failure inpatient service and planning to follow up at UMMC outpatient heart failure clinic

Exclusion Criteria:

  • Patients who are already on ivabradine
  • Patients who are not willing to follow-up with UMMC outpatient heart failure team

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intervention
Drug: Ivabradine
Ivabradine administration--tablets given 5 mg twice daily for 2 weeks, then 7.5 mg twice daily
Placebo Comparator: Control
Drug: Placebos
Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cardiac biomarkers
Time Frame: One month
NT-pro BNP and high sensitivity troponin
One month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Echocardiogram
Time Frame: 2 weeks, and one month
ejection fraction (%)
2 weeks, and one month
6-minute walk test
Time Frame: 2 weeks, and one month
Distance walked (meters) in 6 minutes
2 weeks, and one month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Maryland, Baltimore

Collaborators

Stanford University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

October 1, 2020

Primary Completion (Actual)

August 31, 2021

Study Completion (Actual)

August 31, 2021

Study Registration Dates

First Submitted

August 3, 2018

First Submitted That Met QC Criteria

August 14, 2018

First Posted (Actual)

August 15, 2018

Study Record Updates

Last Update Posted (Actual)

December 12, 2024

Last Update Submitted That Met QC Criteria

December 6, 2024

Last Verified

December 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HP-00080414

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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