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

Heart Failure Clinical Trial

— DECISION  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03783429
• Other study ID #: DECISION trial
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: July 1, 2020
• Est. completion date: July 2025

Study information

• Verified date: December 2023
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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%).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 982
• Est. completion date: July 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure

Intervention

Drug:
• Digoxin
Digoxin tablets will be given orally
• Placebos
Placebo tablets will be given orally

Locations

Country	Name	City	State
Netherlands	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	Haaglanden Medisch Centrum	Den Haag
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	Elisabeth-Tweesteden Ziekenhuis	Tilburg
Netherlands	Diak. Utrecht	Utrecht
Netherlands	Máxima Medisch Centrum	Veldhoven
Netherlands	Zaans Medisch Centrum	Zaandam

Sponsors (6)

Lead Sponsor	Collaborator
University Medical Center Groningen	Disphar International B.V., Netherlands Heart Foundation, Teva Nederland BV, Tiofarma BV, Werkgroep Cardiologische centra Nederland

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	All-cause hospitalizations		Median of 3 years
Other	Unscheduled cardiovascular hospital visits		Median of 3 years
Other	Days alive out of hospital		Median of 3 years
Other	Quality of Life assessed by the EUROQOL-5D-5L questionnaire	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
Other	Heart rate in both AF and sinus rhythm		Median of 3 years
Other	To assess side effects (SUSARs) associated with study medication		Median of 3 years
Other	Initiation of (recurrence of) AF in patients with sinus rhythm at baseline		Median of 3 years
Other	Conversion to sinus rhythm and maintenance of sinus rhythm in patients with AF at baseline		Median of 3 years
Primary	Composite of repeated HF hospitalizations, urgent HF Visits, and cardiovascular death		Median of 3 years
Secondary	All-cause mortality		Median of 3 years
Secondary	Cardiovascular death		Median of 3 years
Secondary	(Repeated) HF hospitalization		Median of 3 years
Secondary	Cost-effectiveness assessed by the Medical Consumption Questionnaire		Median of 3 years
Secondary	Urgent HF hospital visits		Median of 3 years