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

Phase 4

Active, not recruiting

• Conditions: Heart Failure
• Interventions: Drug: Digoxin; Drug: Placebos

• Registration Number: NCT03783429
• Lead Sponsor: University Medical Center Groningen

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%).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-12-13
• Study First Submitted QC: 2018-12-18
• Study First Posted: 2018-12-21
• Study Start: 2020-07-01
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-11
• Last Update Posted: 2023-12-12
• Primary Completion: 2025-07
• Study Completion: 2025-07

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 982

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention group	Digoxin	The intervention group will receive low-dose digoxin
Placebo group	Placebos	The placebo group will receive a matching placebo

Primary Outcome Measures

Name	Time	Method
Composite of repeated HF hospitalizations, urgent HF Visits, and cardiovascular death	Median of 3 years

Secondary Outcome Measures

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

Trial Locations

Locations (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

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