Clinical trial NCT01398371: Digoxin Withdrawal in Stable 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Heart Failure
Keywords: Heart failure
Digoxin withdrawal
Lead sponsor: The Alfred
Sponsor class: OTHER
First posted: 2011-07-20
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: NYHA Heart Failure class
timeFrame: after 12 wks of treatment
Secondary outcomes:
measure: 6 minute walk test
timeFrame: after 12 wks of treatment
measure: Quality of Life
timeFrame: After 12 weeks of treatment
measure: Change in BNP
timeFrame: After 12 weeks of treatment
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Clinical Pharmacology, Alfred Hospital
state: Victoria
Study officials:
affiliation: Alfred Hospital / Monash University
name: Henry Krum, MBBS, FRACP, PhD
role: PRINCIPAL_INVESTIGATOR
References: