Digoxin Evaluation in Chronic Heart Failure: Investigational Study In Outpatients in the Netherlands
DECISION
1 other identifier
interventional
982
1 country
44
Brief Summary
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%).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4 heart-failure
Started Jul 2020
Longer than P75 for phase_4 heart-failure
44 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 13, 2018
CompletedFirst Posted
Study publicly available on registry
December 21, 2018
CompletedStudy Start
First participant enrolled
July 1, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 13, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
November 13, 2025
CompletedApril 27, 2026
April 1, 2026
5.4 years
December 13, 2018
April 21, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
To demonstrate whether low-dose digoxin compared to placebo reduces the rate of the composite CV outcome
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)
Median of 3 years
Secondary Outcomes (7)
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
Median of 3 years
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
Median of 3 years
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
Median of 3 years
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
Median of 3 years
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
Median of 3 years
- +2 more secondary outcomes
Other Outcomes (8)
To determine whether low-dose digoxin compared to placebo improves the exploratory outcomes: all-cause hospitalizations and urgent hospital visits
Median of 3 years
To determine whether low-dose digoxin compared to placebo improves the exploratory outcomes: days alive and out of hospital
Median of 3 years
To determine whether low-dose digoxin compared to placebo improves the exploratory outcomes: Quality of Life assessed by the EUROQOL-5D-5L questionnaire
Median of 3 years
- +5 more other outcomes
Study Arms (2)
Intervention group
ACTIVE COMPARATORThe intervention group will receive low-dose digoxin
Placebo group
PLACEBO COMPARATORThe placebo group will receive a matching placebo
Interventions
Eligibility Criteria
You may qualify if:
- 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)
You may not qualify if:
- 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
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University Medical Center Groningenlead
- Disphar International B.V.collaborator
- Teva Nederland BVcollaborator
- Netherlands Heart Foundationcollaborator
- Werkgroep Cardiologische centra Nederlandcollaborator
- Tiofarma BVcollaborator
Study Sites (44)
Noordwest Ziekenhuisgroep
Alkmaar, Netherlands
Zorggroep Twente
Almelo, Netherlands
Meander Medisch Centrum
Amersfoort, Netherlands
BovenIJ Ziekenhuis
Amsterdam, Netherlands
Gelre Ziekenhuizen
Apeldoorn, Netherlands
Rijnstate Ziekenhuis
Arnhem, Netherlands
Rode Kruis Ziekenhuis
Beverwijk, Netherlands
Tergooi
Blaricum, Netherlands
Amphia Ziekenhuis
Breda, Netherlands
Ijsselland Ziekenhuis
Capelle aan den IJssel, Netherlands
Reinier de Graaf Gasthuis
Delft, Netherlands
Deventer Ziekenhuis
Deventer, Netherlands
Van Weel Bethesda
Dirksland, Netherlands
Slingeland Ziekenhuis
Doetinchem, Netherlands
Ziekenhuis Gelderse Vallei
Ede, Netherlands
Scheper Ziekenhuis
Emmen, Netherlands
Admiraal de Ruyter Ziekenhuis
Goes, Netherlands
Beatrix Ziekenhuis
Gorinchem, Netherlands
Groene Hart Ziekenhuis
Gouda, Netherlands
Martini Ziekenhuis
Groningen, Netherlands
University Medical Center Groningen
Groningen, Netherlands
Spaarne Gasthuis
Haarlem, Netherlands
Saxenburgh MC
Hardenberg, Netherlands
Ziekenhuis St Jansdal
Harderwijk, Netherlands
Zuyderland Medisch Centrum
Heerlen, Netherlands
Elkerliek Ziekenhuis
Helmond, Netherlands
Bethesda
Hoogeveen, Netherlands
Medisch Centrum Leeuwarden
Leeuwarden, Netherlands
Alrijne Ziekenhuis
Leiden, Netherlands
Maastricht UMC+
Maastricht, Netherlands
Isala Diaconessenhuis
Meppel, Netherlands
Radboud University Medical Center
Nijmegen, Netherlands
Bravis ziekenhuis
Roosendaal, Netherlands
Erasmus Medisch Centrum
Rotterdam, Netherlands
Franciscus Gasthuis
Rotterdam, Netherlands
Ikazia Ziekenhuis
Rotterdam, Netherlands
Franciscus Vlietland
Schiedam, Netherlands
Antonius Ziekenhuis Sneek
Sneek, Netherlands
Refaja
Stadskanaal, Netherlands
Haaglanden Medisch Centrum
The Hague, Netherlands
Elisabeth-Tweesteden Ziekenhuis
Tilburg, Netherlands
Diak. Utrecht
Utrecht, Netherlands
Máxima Medisch Centrum
Veldhoven, Netherlands
Zaans Medisch Centrum
Zaandam, Netherlands
Related Publications (1)
van Veldhuisen DJ, Rienstra M, Mosterd A, Alings AM, van Asselt ADJ, Bouvy ML, Tijssen JGP, Schaap J, van der Wall EE, Voors AA, Boorsma EM, Lok DJA, Crijns HJGM, Schut A, Vijver MAT, Voordes GHD, de Vos AH, Maas-Soer EL, Smit NW, Touw DJ, Samuel M, van der Meer P; DECISION Investigators and Committees. Efficacy and safety of low-dose digoxin in patients with heart failure. Rationale and design of the DECISION trial. Eur J Heart Fail. 2024 Oct;26(10):2223-2230. doi: 10.1002/ejhf.3428. Epub 2024 Aug 30.
PMID: 39212246DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Michiel Rienstra, MD, PhD
University Medical Center Groningen
- PRINCIPAL INVESTIGATOR
Peter van der Meer, MD, PhD
University Medical Center Groningen
- PRINCIPAL INVESTIGATOR
Dirk J van Veldhuisen, MD, PhD
University Medical Center Groningen
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- Double blind, placebo controlled
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Prof. Dr.
Study Record Dates
First Submitted
December 13, 2018
First Posted
December 21, 2018
Study Start
July 1, 2020
Primary Completion
November 13, 2025
Study Completion
November 13, 2025
Last Updated
April 27, 2026
Record last verified: 2026-04