Digoxin Evaluation in Chronic Heart Failure: Investigational Study In Outpatients in the Netherlands
- 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
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 982
-
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)
- 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
- Use of digoxin ≤6 months prior to inclusion
- Participation in another (intervention) clinical trial (registry studies not included)
- 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)
Gelre Ziekenhuizen
🇳🇱Apeldoorn, Netherlands
Ziekenhuis Gelderse Vallei
🇳🇱Ede, Netherlands
Groene Hart Ziekenhuis
🇳🇱Gouda, Netherlands
Elisabeth-Tweesteden Ziekenhuis
🇳🇱Tilburg, Netherlands
Zaans Medisch Centrum
🇳🇱Zaandam, Netherlands
Diak. Utrecht
🇳🇱Utrecht, Netherlands
Noordwest Ziekenhuisgroep
🇳🇱Alkmaar, Netherlands
Zorggroep Twente
🇳🇱Almelo, Netherlands
Haaglanden Medisch Centrum
🇳🇱Den Haag, Netherlands
Van Weel Bethesda
🇳🇱Dirksland, Netherlands
Slingeland Ziekenhuis
🇳🇱Doetinchem, Netherlands
Saxenburgh MC
🇳🇱Hardenberg, Netherlands
Scheper Ziekenhuis
🇳🇱Emmen, Netherlands
Beatrix Ziekenhuis
🇳🇱Gorinchem, Netherlands
Medisch Centrum Leeuwarden
🇳🇱Leeuwarden, Netherlands
Maastricht UMC+
🇳🇱Maastricht, Netherlands
Erasmus Medisch Centrum
🇳🇱Rotterdam, Netherlands
Admiraal de Ruyter Ziekenhuis
🇳🇱Goes, Netherlands
Martini Ziekenhuis
🇳🇱Groningen, Netherlands
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Bethesda
🇳🇱Hoogeveen, Netherlands
Alrijne Ziekenhuis
🇳🇱Leiden, Netherlands
Radboud University Medical Center
🇳🇱Nijmegen, Netherlands
Bravis ziekenhuis
🇳🇱Roosendaal, Netherlands
Ikazia Ziekenhuis
🇳🇱Rotterdam, Netherlands
Franciscus Vlietland
🇳🇱Schiedam, Netherlands
Antonius Ziekenhuis Sneek
🇳🇱Sneek, Netherlands
Máxima Medisch Centrum
🇳🇱Veldhoven, Netherlands
Refaja
🇳🇱Stadskanaal, Netherlands
Tergooi
🇳🇱Blaricum, Netherlands
Meander Medisch Centrum
🇳🇱Amersfoort, Netherlands
BovenIJ Ziekenhuis
🇳🇱Amsterdam, Netherlands
Rijnstate Ziekenhuis
🇳🇱Arnhem, Netherlands
Rode Kruis Ziekenhuis
🇳🇱Beverwijk, Netherlands
Amphia Ziekenhuis
🇳🇱Breda, Netherlands
Ijsselland Ziekenhuis
🇳🇱Capelle Aan Den IJssel, Netherlands
Reinier de Graaf Gasthuis
🇳🇱Delft, Netherlands
Deventer Ziekenhuis
🇳🇱Deventer, Netherlands
Spaarne Gasthuis
🇳🇱Haarlem, Netherlands
Ziekenhuis St Jansdal
🇳🇱Harderwijk, Netherlands
Zuyderland Medisch Centrum
🇳🇱Heerlen, Netherlands
Elkerliek Ziekenhuis
🇳🇱Helmond, Netherlands
Isala Diaconessenhuis
🇳🇱Meppel, Netherlands
Franciscus Gasthuis
🇳🇱Rotterdam, Netherlands