Digoxin Evaluation in Chronic Heart Failure: Investigational Study In Outpatients in the Netherlands
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 982
- 试验地点
- 46
- 主要终点
- Composite of repeated HF hospitalizations, urgent HF Visits, and cardiovascular death
研究概览
简要总结
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%).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double blind, placebo controlled
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18year
- •Outpatients with chronic HF, New York Heart Association [NYHA] class II - ambulatory IV
- •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)
排除标准
- •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
研究组 & 干预措施
Placebo group
The placebo group will receive a matching placebo
干预措施: Placebos (Drug)
Intervention group
The intervention group will receive low-dose digoxin
干预措施: Digoxin (Drug)
结局指标
主要结局
Composite of repeated HF hospitalizations, urgent HF Visits, and cardiovascular death
时间窗: Median of 3 years
To demonstrate whether low-dose digoxin compared to placebo reduces the rate of the composite CV outcome
时间窗: Median of 3 years
The composite of total worsening heart failure events (with an event defined as a first or recurrent unplanned hospitalization or urgent visit for heart failure) and death from cardiovascular causes (amount of events)
次要结局
- 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)
- To determine whether low-dose digoxin compared to placebo reduces the rate of the ranked clinical outcomes: composite of all repeated HF hospitalizations and repeated urgent HF visits(Median of 3 years)
- To determine whether low-dose digoxin compared to placebo reduces the rate of the ranked clinical outcomes: composite of all repeated CV hospitalizations and repeated urgent CV hospital visits(Median of 3 years)
- To determine whether low-dose digoxin compared to placebo reduces the rate of the ranked clinical outcomes: first-time occurrence of any of the composite of CV-mortality, HF hospitalization or urgent HF hospital visit(Median of 3 years)
- To determine whether low-dose digoxin compared to placebo reduces the rate of the ranked clinical outcomes: first-time occurrence of any of the composite of all-cause mortality, HF hospitalization or urgent HF hospital visit(Median of 3 years)
- To determine whether low-dose digoxin compared to placebo reduces the rate of the ranked clinical outcomes: first-time occurrence of any of the composite of HF hospitalization or urgent HF hospital visit(Median of 3 years)
- To determine whether low-dose digoxin compared to placebo reduces the rate of the ranked clinical outcomes: first time event to CV mortality(Median of 3 years)
- To determine whether low-dose digoxin compared to placebo reduces the rate of the ranked clinical outcomes: first-time event to all-cause mortality(Median of 3 years)
研究者
M. Rienstra
Prof. Dr.
University Medical Center Groningen