Digoxin Withdrawal in Stable Heart Failure

Condition(s) targeted: Heart Failure

Intervention: Withdrawal of digoxin (Drug); Digoxin (Drug)

Phase: N/A

Status: Recruiting

Sponsored by: The Alfred

Official(s) and/or principal investigator(s):
Henry Krum, MBBS, FRACP, PhD, Principal Investigator, Affiliation: Alfred Hospital / Monash University

Overall contact:
Henry Krum, MBBS, FRACP, PhD, Phone: +61 3 9903 0042, Email: henry.krum@monash.edu

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.

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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Primary outcome: NYHA Heart Failure class

Secondary outcome:

6 minute walk test

Quality of Life

Change in BNP

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Henry Krum, MBBS, FRACP, PhD, Phone: +61 3 9903 0042, Email: henry.krum@monash.edu

Clinical Pharmacology, Alfred Hospital, Melbourne, Victoria 3004, Australia; Recruiting
Henry Krum, MBBS, FRACP, PhD, Phone: +61 3 9903 0042, Email: henry.krum@monash.edu
Ingrid Hopper, MBBS, FRACP, Phone: +61 3 9076 8542, Email: i.hopper@alfred.org.au

Starting date: August 2011
Last updated: August 8, 2012