Systematic Withdrawal of Neurohumoral Blocker Therapy in Optimally Responding CRT Patients (STOP-CRT)

Hasselt University

Status and phase: Completed; Phase 4

Conditions: Heart Failure (HF)

Treatments: Drug: beta blockers; Drug: RAAS blockers

Study type: Interventional

Funder types: Other

Identifiers

NCT02200822

ZOL-STOP-CRT

Details and patient eligibility

About

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of cardiac resynchronization therapy, device treatment is sufficient and neurohumoral blocker therapy can safely be withdrawn

Enrollment: 80 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• ≥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

Exclusion criteria

• 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%)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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80 participants in 4 patient groups

non-intervention arm

No Intervention group

Description:

continuation of neurohumoral blocker therapy based on maximum tolerated guideline recommended dose (this group is the control arm for as well withdrawal of beta blocker therapy as withdrawal of RAAS blocker therapy)

withdrawal of beta blockers

Active Comparator group

Description:

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

Treatment:

Drug: beta blockers

withdrawal of RAAS blockers

Active Comparator group

Description:

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

Treatment:

Drug: RAAS blockers

withdrawal of RAAS - and beta blockers

Active Comparator group

Description:

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

Treatment:

Drug: beta blockers

Drug: RAAS blockers