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

December 11, 2023 updated by: M. Rienstra, University Medical Center Groningen
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%).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

982

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

      • Alkmaar, Netherlands
        • Noordwest Ziekenhuisgroep
      • Almelo, Netherlands
        • Zorggroep Twente
      • Amersfoort, Netherlands
        • Meander Medisch Centrum
      • Amsterdam, Netherlands
        • BovenIJ Ziekenhuis
      • Apeldoorn, Netherlands
        • Gelre Ziekenhuizen
      • Arnhem, Netherlands
        • Rijnstate Ziekenhuis
      • Beverwijk, Netherlands
        • Rode Kruis Ziekenhuis
      • Blaricum, Netherlands
        • Tergooi
      • Breda, Netherlands
        • Amphia ziekenhuis
      • Capelle Aan Den IJssel, Netherlands
        • IJsselland Ziekenhuis
      • Delft, Netherlands
        • Reinier de Graaf Gasthuis
      • Den Haag, Netherlands
        • Haaglanden Medisch Centrum
      • Deventer, Netherlands
        • Deventer Ziekenhuis
      • Dirksland, Netherlands
        • Van Weel Bethesda
      • Doetinchem, Netherlands
        • Slingeland Ziekenhuis
      • Ede, Netherlands
        • Ziekenhuis Gelderse Vallei
      • Emmen, Netherlands
        • Scheper Ziekenhuis
      • Goes, Netherlands
        • Admiraal de Ruyter Ziekenhuis
      • Gorinchem, Netherlands
        • Beatrix Ziekenhuis
      • Gouda, Netherlands
        • Groene Hart Ziekenhuis
      • Groningen, Netherlands
        • Martini Ziekenhuis
      • Groningen, Netherlands
        • University Medical Center Groningen
      • Haarlem, Netherlands
        • Spaarne Gasthuis
      • Hardenberg, Netherlands
        • Saxenburgh MC
      • Harderwijk, Netherlands
        • Ziekenhuis St Jansdal
      • Heerlen, Netherlands
        • Zuyderland Medisch Centrum
      • Helmond, Netherlands
        • Elkerliek Ziekenhuis
      • Hoogeveen, Netherlands
        • Bethesda
      • Leeuwarden, Netherlands
        • Medisch Centrum Leeuwarden
      • Leiden, Netherlands
        • Alrijne Ziekenhuis
      • Maastricht, Netherlands
        • Maastricht UMC+
      • Meppel, Netherlands
        • Isala Diaconessenhuis
      • Nijmegen, Netherlands
        • Radboud University Medical Center
      • Roosendaal, Netherlands
        • Bravis Ziekenhuis
      • Rotterdam, Netherlands
        • Erasmus Medisch Centrum
      • Rotterdam, Netherlands
        • Ikazia Ziekenhuis
      • Rotterdam, Netherlands
        • Franciscus Gasthuis
      • Schiedam, Netherlands
        • Franciscus Vlietland
      • Sneek, Netherlands
        • Antonius Ziekenhuis Sneek
      • Stadskanaal, Netherlands
        • Refaja
      • Tilburg, Netherlands
        • Elisabeth-TweeSteden Ziekenhuis
      • Utrecht, Netherlands
        • Diak. Utrecht
      • Veldhoven, Netherlands
        • Maxima Medisch Centrum
      • Zaandam, Netherlands
        • Zaans Medisch Centrum

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age ≥18year
  2. Outpatients with chronic HF, New York Heart Association [NYHA] class II - ambulatory IV
  3. LVEF<50%
  4. 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.

  5. ≥14 days stable on guideline-recommended therapy (doses and number of therapies as tolerated by each patient)

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Intervention group
The intervention group will receive low-dose digoxin
Digoxin tablets will be given orally
Placebo Comparator: Placebo group
The placebo group will receive a matching placebo
Placebo tablets will be given orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Composite of repeated HF hospitalizations, urgent HF Visits, and cardiovascular death
Time Frame: Median of 3 years
Median of 3 years

Secondary Outcome Measures

Outcome Measure
Time Frame
All-cause mortality
Time Frame: Median of 3 years
Median of 3 years
Cardiovascular death
Time Frame: Median of 3 years
Median of 3 years
(Repeated) HF hospitalization
Time Frame: Median of 3 years
Median of 3 years
Cost-effectiveness assessed by the Medical Consumption Questionnaire
Time Frame: Median of 3 years
Median of 3 years
Urgent HF hospital visits
Time Frame: Median of 3 years
Median of 3 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
All-cause hospitalizations
Time Frame: Median of 3 years
Median of 3 years
Unscheduled cardiovascular hospital visits
Time Frame: Median of 3 years
Median of 3 years
Days alive out of hospital
Time Frame: Median of 3 years
Median of 3 years
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.

Median of 3 years
Heart rate in both AF and sinus rhythm
Time Frame: Median of 3 years
Median of 3 years
To assess side effects (SUSARs) associated with study medication
Time Frame: Median of 3 years
Median of 3 years
Initiation of (recurrence of) AF in patients with sinus rhythm at baseline
Time Frame: Median of 3 years
Median of 3 years
Conversion to sinus rhythm and maintenance of sinus rhythm in patients with AF at baseline
Time Frame: Median of 3 years
Median of 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • 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 record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2020

Primary Completion (Estimated)

July 1, 2025

Study Completion (Estimated)

July 1, 2025

Study Registration Dates

First Submitted

December 13, 2018

First Submitted That Met QC Criteria

December 18, 2018

First Posted (Actual)

December 21, 2018

Study Record Updates

Last Update Posted (Estimated)

December 12, 2023

Last Update Submitted That Met QC Criteria

December 11, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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