Digoxin Withdrawal in Stable Heart Failure

A Randomised, Blinded, Placebo Controlled Trial to Assess the Effect of Digoxin Withdrawal in Stable Heart Failure Patients Receiving Optimal Background Therapy

Heart failure is a chronic condition in which the heart fails to function as a pump to move blood around the body. This sets up a complex physiologic response to compensate, which include activation of many hormonal mechanisms which result in fluid accumulation.

In recent years, medications to block the hormonal response to heart failure are given as standard drugs, and these include ACE inhibitors, and beta blockers. Mortality is reduced with these medications, as well as symptoms improved.

Medications that were traditionally used in heart failure include diuretics, which cause fluid loss, and digoxin, which causes the heart to pump harder. These medications were introduced before clinical trials as we know them now were run. Since the introduction of ACE inhibitors and beta blockers, it is not clear whether there is still a role for digoxin.

In this study, we plan to withdraw digoxin from patients with stable heart failure in normal rhythm, taking stable doses of ACE inhibitors and beta blockers, in a closely monitored environment and watch for the effect of this on heart failure.

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Drug: Digoxin; Drug: Withdrawal of digoxin

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Clinical Pharmacology, Alfred Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Over the age of 18 years
2. In sinus rhythm at the time of randomisation
3. Have a LVEF <0.45 and a left ventricular end-diastolic dimension >60 mm or >34 mm/m2
4. Are receiving ACE inhibitor, β-blocker and diuretic therapy at the optimal doses.
5. Has been receiving digoxin therapy for at least 3 months at a dose that results in digoxin plasma levels of 0.4-0.8 on 2 consecutive blood tests (at least 1 weeks apart) prior to randomisation. The dose of digoxin must remain stable for at least 2 weeks prior to randomisation.

6. Documented, stable heart failure. Must have at least 1 of the following:

   • Hospitalised with a discharge diagnosed of heart failure in the last 6 months
   • Evidence of pulmonary congestion on chest X-ray
   • Evidence of heart failure on echocardiogram
   • Evidence of heart failure on ECG
7. Willing and able to provide informed consent

Exclusion Criteria:

1. Systolic BP >160mmHg or <90mmHg
2. Diastolic BP >95mmHg
3. Uncorrected primary valvular disease
4. Active myocarditis
5. Obstructive or restrictive Cardiomyopathy
6. Exercise capacity limited by other factors not including dyspnoea
7. Myocardial infarction within the previous 6 months
8. Stroke within the previous 12 months
9. Hospitalisation within one month of randomisation
10. A history of supraventricular arrhythmia or sustained ventricular arrhythmia
11. Claudication
12. Severe primary pulmonary (VC <1.5L), renal or hepatic disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Stable digoxin therapy; Participants need to have been receiving digoxin therapy for at least 3 months at a dose that results in digoxin plasma levels of 0.4-0.8 on 2 consecutive blood tests (at least 1 weeks apart) prior to randomisation. The dose of digoxin must remain stable for at least 2 weeks prior to randomisation.	Drug: Digoxin; Stable digoxin therapy which produces a digoxin plasma level of 0.4-0.8.
Experimental: Digoxin withdrawal; Participants will receive a placebo for 4 weeks.	Drug: Withdrawal of digoxin; Participants currently receiving digoxin for heart failure will have their digoxin stopped for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
NYHA Heart Failure class	after 12 wks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6 minute walk test		after 12 wks of treatment
Quality of Life	Standard questionnaires will be used	After 12 weeks of treatment
Change in BNP		After 12 weeks of treatment

Collaborators and Investigators

• Sponsor: The Alfred
• Investigators: Principal Investigator: Henry Krum, MBBS, FRACP, PhD, Alfred Hospital / Monash University

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: July 19, 2011
• First Submitted That Met QC Criteria: July 19, 2011
• First Posted (Estimate): July 20, 2011

Study Record Updates

• Last Update Posted (Estimate): June 1, 2016
• Last Update Submitted That Met QC Criteria: May 30, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Heart failure; Digoxin withdrawal
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Enzyme Inhibitors; Protective Agents; Cardiotonic Agents; Digoxin
• Other Study ID Numbers: 257/11; Pending (Other Grant/Funding Number: American Acedemy of Optometry Foundation (AAOF))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No