Digoxin Withdrawal in Stable Heart Failure

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by The Alfred
Sponsor:
Information provided by (Responsible Party):
Henry Krum, The Alfred
ClinicalTrials.gov Identifier:
NCT01398371
First received: July 19, 2011
Last updated: May 29, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention
Heart Failure
Drug: Withdrawal of digoxin
Drug: Digoxin

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: A Randomised, Blinded, Placebo Controlled Trial to Assess the Effect of Digoxin Withdrawal in Stable Heart Failure Patients Receiving Optimal Background Therapy

Resource links provided by NLM:


Further study details as provided by The Alfred:

Primary Outcome Measures:
  • NYHA Heart Failure class [ Time Frame: after 12 wks of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 6 minute walk test [ Time Frame: after 12 wks of treatment ] [ Designated as safety issue: No ]
  • Quality of Life [ Time Frame: After 12 weeks of treatment ] [ Designated as safety issue: No ]
    Standard questionnaires will be used

  • Change in BNP [ Time Frame: After 12 weeks of treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: August 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01398371

Contacts
Contact: Henry Krum, MBBS, FRACP, PhD +61 3 9903 0042 henry.krum@monash.edu
Contact: Ingrid Hopper, MBBS, FRACP +61 3 9076 8542 i.hopper@alfred.org.au

Locations
Australia, Victoria
Clinical Pharmacology, Alfred Hospital Recruiting
Melbourne, Victoria, Australia, 3004
Contact: Henry Krum, MBBS, FRACP, PhD    +61 3 9903 0042    henry.krum@monash.edu   
Contact: Ingrid Hopper, MBBS, FRACP    +61 3 9076 8542    i.hopper@alfred.org.au   
Sponsors and Collaborators
The Alfred
Investigators
Principal Investigator: Henry Krum, MBBS, FRACP, PhD Alfred Hospital / Monash University
  More Information

No publications provided

Responsible Party: Henry Krum, Prof Henry Krum, The Alfred
ClinicalTrials.gov Identifier: NCT01398371     History of Changes
Other Study ID Numbers: 257/11, Pending
Study First Received: July 19, 2011
Last Updated: May 29, 2013
Health Authority: Australia: Human Research Ethics Committee

Keywords provided by The Alfred:
Heart failure
Digoxin withdrawal

Additional relevant MeSH terms:
Heart Failure
Cardiovascular Diseases
Heart Diseases
Digoxin
Anti-Arrhythmia Agents
Cardiotonic Agents
Cardiovascular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014