Systematic Withdrawal of Neurohumoral Blocker Therapy in Optimally Responding CRT Patients

Phase 4

Completed

• Conditions: Heart Failure (HF)
• Interventions: Drug: beta blockers; Drug: RAAS blockers

• Registration Number: NCT02200822
• Lead Sponsor: Hasselt University

Brief Summary

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of cardiac resynchronization therapy, device treatment is sufficient and neurohumoral blocker therapy can safely be withdrawn

Detailed Description

Not available

Study Timeline

• Study Start: 2014-07
• Study First Submitted: 2014-07-24
• Study First Submitted QC: 2014-07-24
• Study First Posted: 2014-07-25
• Primary Completion: 2019-02
• Study Completion: 2019-02
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-30
• Last Update Posted: 2019-08-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 80

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%)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
withdrawal of beta blockers	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
withdrawal of RAAS blockers	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
withdrawal of RAAS - and beta blockers	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
withdrawal of RAAS - and beta blockers	RAAS 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

Primary Outcome Measures

Name	Time	Method
a > 15% increase in left ventricular end systolic volume	at 12 months

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Ziekenhuis Oost Limburg; 🇧🇪 Genk, Limburg, Belgium