Systematic Withdrawal of Neurohumoral Blocker Therapy in Optimally Responding Patients to Cardiac Resynchronization Therapy: the STOP-CRT Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- a > 15% increase in left ventricular end systolic volume
研究概览
简要总结
The primary objective of this study is to demonstrate that in patients with recuperated/normalized left ventricular function, defined as an ejection fraction (EF) ≥ 50%, after implantation of cardiac resynchronization therapy, device treatment is sufficient and neurohumoral blocker therapy can safely be withdrawn
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- None
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
- •≥18 years
- •CRT implantation
- •based on class I recommendations of ESC (European society of CArdiology) guidelines:
- •Left bundle branch block (LBBB) with QRS duration >150 ms and left ventricular ejection fraction (LVEF) ≤35% who remained NYHA functional class II, III and ambulatory IV despite adequate medical treatment
- •LBBB with QRS duration 120-150 ms and LVEF ≤ 35% who remain in NYHA functional class II, III and ambulatory IV despite adequate medical treatment
- •At the moment of inclusion: ≥ 6 months after implantation
- •At the moment of inclusion: normalised LVEF (≥ 50%), LVIDD/BSA (left ventricular internal diastolic diameter indexed to body surface area) ≤3.2 cm/m²(woman) en ≤3.1 cm/m² (men) or LVDV/BSA (left ventricular diastolic volume indexed to body surface area) ≤75 ml/m² (women) or ≤75 ml/m² (men)
- •euvolemic clinical state and functioning in NYHA class I
排除标准
- •contraindication for withdrawal of ACE-I/ARB such as diabetic nephropathy and proteinuria > 1g / 24 h
- •severe ventricular arrythmia (sustained VT or ventricular fibrillation) occuring at the time LV function was normalized
- •ischemic cardiomyopathy with evidence of scarring (scarring on MRI or severe hypokinesia/akinesia in >1 LV wall segment on echocardiography)
- •known severe coronary atherosclerosis (stenosis ≥ 80%)
研究组 & 干预措施
withdrawal of beta blockers
Intervention arm with systematic withdrawal of beta blocker therapy at a reverse sequence of guideline recommended uptitration.
(this group is the experimental arm for beta blocker withdrawal. This group receives no intervention with regards to the withdrawal of RAAS blockade). Per 2 weeks:
- bisoprolol: 10mg/d → 5 mg/d → 2,5 mg/d → 1,25 mg/d stop
- metoprolol: 200 mg/d → 100 mg/d → 50 mg/d → 25 mg/d → stop
- nebivolol: 10mg/d → 5 mg/d → 2,5 mg/d → 1,25 mg/d stop
- carvedilol: 50 mg bid → 25 mg bid → 12,5 mg bid → 6,25 mg bid → stop
干预措施: beta blockers (Drug)
withdrawal of RAAS blockers
intervention arm with systematic withdrawal of spironolactone followed by withdrawal of ACE-I/ARB at a reverse sequence of guideline recommended uptitration (this group receives no intervention regarding the withdrawal of beta blockers. This group is the experimental arm for withdrawal of RAAS blockers)
-
first spironolactone/eplerenone: per two weeks: 25 mg/d→12,5 mg/d → stop
-
after 2 weeks stop spironolactone/eplerenone start withdrawal of ACE-I/ARB per two weeks:
-
captopril: 50 mg tid→25 mg tid→12,5 mg tid→6,25 mg tid→stop
-
enalapril: 10 mg bid→5 mg bid→2,5 mg bid→1,25 mg bid→stop
-
lisinopril: 20 mg/d→10 mg/d→5 mg/d→2,5 mg/d→stop
-
ramipril: 10 mg/d→5 mg/d→2,5 mg/d→1,25 mg/d→stop
-
candesartan: 32 mg/d→16 mg/d→8 mg/d→4 m/d→stop
-
valsartan: 160 mg bid→80 mg bid→40 mg bid→20 mg bid→stop
干预措施: RAAS blockers (Drug)
withdrawal of RAAS - and beta blockers
intervention arm with systematic withdrawal of spironolactone, secondly ACE-I/ARB and finally beta blockers. (this group is the experimental group for both study interventions (withdrawal of beta blockers and RAAS blockers)
- First: spironolactone/eplerenone cfr reduction schedule supra
- After 2 weeks of stop spironolactone withdrawal of ACE-I or ARB cfr reduction schedule supra
- After 2 weeks of stop ACE-I/ARB withdrawal of beta blocker cfr reduction schedule supra
干预措施: beta blockers (Drug)
withdrawal of RAAS - and beta blockers
intervention arm with systematic withdrawal of spironolactone, secondly ACE-I/ARB and finally beta blockers. (this group is the experimental group for both study interventions (withdrawal of beta blockers and RAAS blockers)
- First: spironolactone/eplerenone cfr reduction schedule supra
- After 2 weeks of stop spironolactone withdrawal of ACE-I or ARB cfr reduction schedule supra
- After 2 weeks of stop ACE-I/ARB withdrawal of beta blocker cfr reduction schedule supra
干预措施: RAAS blockers (Drug)
结局指标
主要结局
a > 15% increase in left ventricular end systolic volume
时间窗: at 12 months
次要结局
- VO2 max change(at 12 months)
- - Incidence of HF related hospitalizations defined as admission to hospital / presentation to emergency room with need for parental therapy(at 12 months)
- All cause mortality(at 12 months)
研究者
Wilfried Mullens, MD PhD
MD PhD
Hasselt University