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

Sponsor
University Medical Center Groningen (Other)
Overall Status
Recruiting
CT.gov ID
NCT03783429
Collaborator
Disphar International B.V. (Industry), Teva Nederland BV (Other), Tiofarma BV (Other), Netherlands Heart Foundation (Other), WCN (Werkgroep Cardiologische centra Nederland) (Other)
982
Enrollment
45
Locations
2
Arms
60
Anticipated Duration (Months)
21.8
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

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%).

Condition or Disease Intervention/Treatment Phase
Phase 4

Study Design

Study Type:
Interventional
Anticipated Enrollment :
982 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
A national, multicenter, randomized, double-blind placebo controlled, clinical trial.A national, multicenter, randomized, double-blind placebo controlled, clinical trial.
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Double blind, placebo controlled
Primary Purpose:
Treatment
Official Title:
Digoxin Evaluation in Chronic Heart Failure: Investigational Study In Outpatients in the Netherlands
Actual Study Start Date :
Jul 1, 2020
Anticipated Primary Completion Date :
Jul 1, 2025
Anticipated Study Completion Date :
Jul 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Intervention group

The intervention group will receive low-dose digoxin

Drug: Digoxin
Digoxin tablets will be given orally
Placebo Comparator: Placebo group

The placebo group will receive a matching placebo

Drug: Placebos
Placebo tablets will be given orally

Outcome Measures

Primary Outcome Measures

  1. Composite of repeated HF hospitalizations, urgent HF Visits, and cardiovascular death [Median of 3 years]

Secondary Outcome Measures

  1. All-cause mortality [Median of 3 years]

  2. Cardiovascular death [Median of 3 years]

  3. (Repeated) HF hospitalization [Median of 3 years]

  4. Cost-effectiveness assessed by the Medical Consumption Questionnaire [Median of 3 years]

  5. Urgent HF hospital visits [Median of 3 years]

Other Outcome Measures

  1. All-cause hospitalizations [Median of 3 years]

  2. Unscheduled cardiovascular hospital visits [Median of 3 years]

  3. Days alive out of hospital [Median of 3 years]

  4. Quality of Life assessed by the EUROQOL-5D-5L questionnaire [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.

  5. Heart rate in both AF and sinus rhythm [Median of 3 years]

  6. To assess side effects (SUSARs) associated with study medication [Median of 3 years]

  7. Initiation of (recurrence of) AF in patients with sinus rhythm at baseline [Median of 3 years]

  8. Conversion to sinus rhythm and maintenance of sinus rhythm in patients with AF at baseline [Median of 3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

  1. ≥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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Noordwest Ziekenhuisgroep Alkmaar Netherlands
2 Zorggroep Twente Almelo Netherlands
3 Meander Medisch Centrum Amersfoort Netherlands
4 BovenIJ Ziekenhuis Amsterdam Netherlands
5 Onze Lieve Vrouwe Gasthuis Amsterdam Netherlands
6 Gelre Ziekenhuizen Apeldoorn Netherlands
7 Rijnstate Ziekenhuis Arnhem Netherlands
8 Rode Kruis Ziekenhuis Beverwijk Netherlands
9 Tergooi Blaricum Netherlands
10 Amphia Ziekenhuis Breda Netherlands
11 Ijsselland Ziekenhuis Capelle Aan Den IJssel Netherlands
12 Reinier de Graaf Gasthuis Delft Netherlands
13 Haaglanden Medisch Centrum Den Haag Netherlands
14 Deventer Ziekenhuis Deventer Netherlands
15 Van Weel Bethesda Dirksland Netherlands
16 Slingeland Ziekenhuis Doetinchem Netherlands
17 Ziekenhuis Gelderse Vallei Ede Netherlands
18 Scheper Ziekenhuis Emmen Netherlands
19 Admiraal de Ruyter Ziekenhuis Goes Netherlands
20 Beatrix Ziekenhuis Gorinchem Netherlands
21 Groene Hart Ziekenhuis Gouda Netherlands
22 Martini Ziekenhuis Groningen Netherlands
23 University Medical Center Groningen Groningen Netherlands
24 Spaarne Gasthuis Haarlem Netherlands
25 Saxenburgh MC Hardenberg Netherlands
26 Ziekenhuis St Jansdal Harderwijk Netherlands
27 Zuyderland Medisch Centrum Heerlen Netherlands
28 Elkerliek Ziekenhuis Helmond Netherlands
29 Bethesda Hoogeveen Netherlands
30 Medisch Centrum Leeuwarden Leeuwarden Netherlands
31 Alrijne Ziekenhuis Leiden Netherlands
32 Maastricht UMC+ Maastricht Netherlands
33 Isala Diaconessenhuis Meppel Netherlands
34 Radboud University Medical Center Nijmegen Netherlands
35 Bravis ziekenhuis Roosendaal Netherlands
36 Erasmus Medisch Centrum Rotterdam Netherlands
37 Franciscus Gasthuis Rotterdam Netherlands
38 Ikazia Ziekenhuis Rotterdam Netherlands
39 Franciscus Vlietland Schiedam Netherlands
40 Antonius Ziekenhuis Sneek Sneek Netherlands
41 Refaja Stadskanaal Netherlands
42 Elisabeth-Tweesteden Ziekenhuis Tilburg Netherlands
43 Diak. Utrecht Utrecht Netherlands
44 Máxima Medisch Centrum Veldhoven Netherlands
45 Zaans Medisch Centrum Zaandam Netherlands

Sponsors and Collaborators

  • University Medical Center Groningen
  • Disphar International B.V.
  • Teva Nederland BV
  • Tiofarma BV
  • Netherlands Heart Foundation
  • WCN (Werkgroep Cardiologische centra Nederland)

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 Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
M. Rienstra, Prof. Dr., University Medical Center Groningen
ClinicalTrials.gov Identifier:
NCT03783429
Other Study ID Numbers:
  • DECISION trial
First Posted:
Dec 21, 2018
Last Update Posted:
Feb 24, 2022
Last Verified:
Feb 1, 2022
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
Keywords provided by M. Rienstra, Prof. Dr., University Medical Center Groningen
Heart Failure
Digoxin
Atrial fibrillation
Additional relevant MeSH terms:
Heart Failure
Digoxin

Study Results

No Results Posted as of Feb 24, 2022