Digoxin Evaluation in Chronic heart failure: Investigational Study In Outpatients in the Netherlands: DECISION
Project: AF RISK, BIOSTAT-CHF, DECISION, OUTREACH, RACE V, SHE-PREDICTS HF Research line: Atrial Fibrillation, Heart FailureMore about this vacancy
Digoxin is the oldest drug for heart failure (HF), and very cheap. A large trial with digoxin, the DIG trial (NEJM 1997), 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 reduce HF hospitalizations but also decrease mortality in patients with chronic HF. To confirm this and to establish the position of digoxin in the treatment of HF, both in sinus rhythm(SR) and in atrial fibrillation (AF) a randomized, placebo-controlled trial is necessary . We will investigate whether low-level digoxin, aiming for serum concentrations 0.5-0.9 ng/mL, is beneficial in a wide spectrum of patients with HF (LVEF <50%).
Objective: The primary objective is to study whether in chronic HF compared to placebo, low-level digoxin reduces (repeated) HF hospitalizations and cardiovascular mortality, on top of guideline-recommended therapies.
Study design: The proposed trial will be a national, multicenter, randomized, double-blind placebo controlled, clinical trial. We will include an estimated 982 chronic HF patients with LVEF <50%, with at least 1/3 of patients with AF, and 1/3 women, to ensure a sample of the real life HF population. First patient is expected to be enrolled in May 2020.
Study population: Patients aged >18 years, with chronic HF NYHA II to ambulatory IV, LVEF <50%, stable on heart failure medication and serum NT-proBNP concentrations >400pg/mL if SR; >800pg/mL if AF,
Intervention: Patients will be randomized to low-level digoxin or placebo in a double-blinded fashion. Digoxin will be given orally starting at doses of 0.2mg, or 0.1mg, based on age and renal function. No loading dose is given. After 4 weeks serum digoxin concentrations will be measured and dose adjustments will be made if necessary to reach the target range of 0.5-0.9 ng/mL.
Main study endpoint: The primary endpoint is the composite of (repeated) HF hospitalizations and cardiovascular death.
Impact of study: This is the first randomized clinical trial (RCT) with digoxin in HF patients with sinus rhythm in 25 years, and the first RCT ever in HF patients with AF. The results of DECISION will impact HF Guidelines.