Digoxin Withdrawal in Stable Heart Failure

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

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: Withdrawal of digoxin
* Drug: Digoxin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Over the age of 18 years In sinus rhythm at the time of randomisation Have a LVEF <0.45 and a left ventricular end-diastolic dimension >60 mm or >34 mm/m2 Are receiving ACE inhibitor, β-blocker and diuretic therapy at the optimal doses. 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. 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 Willing and able to provide informed consent Exclusion Criteria: Systolic BP >160mmHg or <90mmHg Diastolic BP >95mmHg Uncorrected primary valvular disease Active myocarditis Obstructive or restrictive Cardiomyopathy Exercise capacity limited by other factors not including dyspnoea Myocardial infarction within the previous 6 months Stroke within the previous 12 months Hospitalisation within one month of randomisation A history of supraventricular arrhythmia or sustained ventricular arrhythmia Claudication Severe primary pulmonary (VC <1.5L), renal or hepatic disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Stable digoxin therapy<br>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<br>* Stable digoxin therapy which produces a digoxin plasma level of 0.4-0.8.<br>|
| Experimental: Digoxin withdrawal<br>Participants will receive a placebo for 4 weeks. | Drug: Withdrawal of digoxin<br>* Participants currently receiving digoxin for heart failure will have their digoxin stopped for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart failure, Digoxin withdrawal