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Completed

NCT Number: NCT03783429

Digoxin Evaluation in Chronic Heart Failure: Investigational Study In Outpatients in the Netherlands

Digoxin is the oldest, market-authorized drug for heart failure (HF), and very cheap. A large trial with digoxin, the DIG trial, executed in the early nineties revealed a highly significant reduction in HF hospitalizations, but no effect on mortality. A post-hoc analysis of the DIG trial suggests that low serum concentrations of digoxin may not only improve HF hospitalizations but also mortality in chronic HF patients. To confirm these retrospective analyses, a prospective, randomized, placebo-controlled trial is necessary to establish the position of digoxin in the contemporary treatment of HF. Therefore, the investigators examine whether low-level, aiming for serum concentrations 0.5-0.9ng/mL, digoxin is beneficial in HF patients with reduced or mid-range ejection fractions (LVEF <50%).

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Key information

Conditions

Heart Failure Arrhythmias, Cardiac Atrial Fibrillation Cardiovascular Diseases Heart Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Noordwest Ziekenhuisgroep, Alkmaar, Netherlands

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age ≥18year
  • Outpatients with chronic HF, New York Heart Association [NYHA] class II - ambulatory IV
  • LVEF<50%
  • Serum NT-proBNP concentrations:

Previous HF hospitalization ≤ 1 year before randomisation ≥400pg/mL if sinus rhythm; ≥800pg/mL if AF Previous HF hospitalization > 1 year before randomisation or in the absence of HF hospitalizations ≥ 600pg/mL if sinus rhythm; ≥1000 pg/mL if AF

BNP concentrations:

Previous HF hospitalization ≤ 1 year before randomisation ≥100pg/mL if sinus rhythm; ≥200pg/mL if AF Previous HF hospitalization > 1 year before randomisation or in absence of HF hospitalization ≥150pg/mL if sinus rhythm; ≥250pg/mL if AF.

  • ≥14 days stable on guideline-recommended therapy (doses and number of therapies as tolerated by each patient)

Exclusion criteria

  • Heart rate ≤60bpm (if sinus rhythm); heart rate ≤70bpm (if AF)
  • History of HF hospitalization ≤7days
  • History of myocardial infarction, myocarditis, percutaneous intervention, RCT, pacemaker/ICD implantation, cardiac surgery or stroke ≤30 days
  • Estimated glomerular filtration rate (eGFR), ≤30ml/min/1.73m2
  • The presence of a mechanical assist device
  • Use of inotropic drugs (dopamine, dobutamine, (nor)adrenaline, and milrinon)
  • Scheduled for mechanical assist device or heart transplant
  • Other non-cardiac conditions with limited life expectancy (≤ duration of the study)
  • Amyloid, hypertrophic obstructive or constrictive cardiomyopathy
  • Accessory atrio-ventricular pathway (e.g. Wolf-Parkinson-White syndrome)
  • (Intermittent) complete heart block or second-degree AV block type Mobitz without pace maker or ICD
  • Severe (grade III/III) aortic valve disease
  • Complex congenital heart disease
  • Proven hypersensitivity to digoxin (prior side effects)
  • Concomitant medication that interacts with digoxin
  • Use of digoxin ≤6 months prior to inclusion
  • Participation in another (intervention) clinical trial (registry studies not included)
  • Women who are pregnant, breastfeeding or may be considering pregnancy during the study period

Treatment and study plan

Digoxin

Drug

Digoxin tablets will be given orally

Placebos

Drug

Placebo tablets will be given orally

Primary outcomes

  1. To demonstrate whether low-dose digoxin compared to placebo reduces the rate of the composite CV outcome

    Time frame: Median of 3 years

    The composite of total worsening heart failure events (with an event defined as a first or recurrent unplanned hospitalization or urgent visit for heart failure) and death from cardiovascular causes (amount of events)

Secondary outcomes

  1. To determine whether low-dose digoxin compared to placebo reduces the rate of the ranked clinical outcomes: composite of all repeated HF hospitalizations and repeated urgent HF visits

    Time frame: Median of 3 years

    composite of all repeated HF hospitalizations and repeated urgent HF visits (amount)

  2. To determine whether low-dose digoxin compared to placebo reduces the rate of the ranked clinical outcomes: composite of all repeated CV hospitalizations and repeated urgent CV hospital visits

    Time frame: Median of 3 years

    composite of all repeated CV hospitalizations and repeated urgent CV hospital visits (amount)

  3. To determine whether low-dose digoxin compared to placebo reduces the rate of the ranked clinical outcomes: first-time occurrence of any of the composite of CV-mortality, HF hospitalization or urgent HF hospital visit

    Time frame: Median of 3 years

    first-time occurrence of any of the composite of CV-mortality, HF hospitalization or urgent HF hospital visit

  4. To determine whether low-dose digoxin compared to placebo reduces the rate of the ranked clinical outcomes: first-time occurrence of any of the composite of all-cause mortality, HF hospitalization or urgent HF hospital visit

    Time frame: Median of 3 years

    first-time occurrence of any of the composite of all-cause mortality, HF hospitalization or urgent HF hospital visit

  5. To determine whether low-dose digoxin compared to placebo reduces the rate of the ranked clinical outcomes: first-time occurrence of any of the composite of HF hospitalization or urgent HF hospital visit

    Time frame: Median of 3 years

    first-time occurrence of any of the composite of HF hospitalization or urgent HF hospital visit

  6. To determine whether low-dose digoxin compared to placebo reduces the rate of the ranked clinical outcomes: first time event to CV mortality

    Time frame: Median of 3 years

    first time event to CV mortality

  7. To determine whether low-dose digoxin compared to placebo reduces the rate of the ranked clinical outcomes: first-time event to all-cause mortality

    Time frame: Median of 3 years

    first-time event to all-cause mortality

Other outcomes

  1. To determine whether low-dose digoxin compared to placebo improves the exploratory outcomes: all-cause hospitalizations and urgent hospital visits

    Time frame: Median of 3 years

    Amount of events per patient years, incidence rate

  2. To determine whether low-dose digoxin compared to placebo improves the exploratory outcomes: days alive and out of hospital

    Time frame: Median of 3 years

    amount of days alive and out of hospital

  3. To determine whether low-dose digoxin compared to placebo improves the exploratory outcomes: Quality of Life assessed by the EUROQOL-5D-5L questionnaire

    Time frame: Median of 3 years

    Quality of Life is assessed by questions about mobility, selfcare, daily activity, pain and anxiety. The questions about mobility, selfcare and daily activity range from 'no problem doing activity' to 'not able to do activity'. The questions about pain and anxiety range from 'not at all present' to 'extremely present'.

    The last question in the questionnaire asks how a person rates his or her health in the present day, ranging from 0-100, where 0 is the worst health imaginable, and 100 is the best health imaginable. EQ5DL index value and EQ5DL VAS score (0-100).

    The EQ-5D-5L is a 2-part instrument, if only one part is used you cannot claim to have used EQ-5D-5L in your publications, therefore this outcome is listed as 1 outcome measure.

  4. To determine whether low-dose digoxin compared to placebo improves the exploratory outcomes: Reported Suspected Unexpected Serious Adverse Reactions (SUSARs)

    Time frame: Median of 3 years

    incidence rate (IR) amount of events per patient years

  5. To determine whether low-dose digoxin compared to placebo improves the exploratory outcomes: Heart rate in both AF and sinus rhythm

    Time frame: Median of 3 years

    in beats per minute

  6. To determine whether low-dose digoxin compared to placebo improves the exploratory outcomes: Initiation of (and/of recurrence of) AF in patients with sinus rhythm at baseline

    Time frame: Median of 3 years

    Amount of events per patient years, incidence rate (IR)

  7. To determine whether low-dose digoxin compared to placebo improves the exploratory outcomes: Conversion to sinus rhythm and maintenance of sinus rhythm in patients with AF at baseline

    Time frame: Median of 3 years

    Amount of events per patient years, incidence rate (IR)

  8. To determine whether low-dose digoxin compared to placebo improves the exploratory outcomes: Implantation of pacemaker, ICD, CRT or LVAD

    Time frame: Median of 3 years

    Amount of events per patient years, incidence rate (IR)

Sponsors and collaborators

Lead sponsor

University Medical Center Groningen

Other

Collaborators

  • Disphar International B.V.
  • Netherlands Heart Foundation
  • Teva Nederland BV
  • Tiofarma BV
  • Werkgroep Cardiologische centra Nederland

Registry information

Acronym: DECISION

Important dates

Study start
2020
Primary completion
2025
Study completion
2025
First posted
Dec 21, 2018
Registry last updated
Apr 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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