Systematic Withdrawal of Neurohumoral Blocker Therapy in Optimally Responding CRT Patients

NCT ID: NCT02200822

Last Updated: 2019-08-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-31
• Study Completion Date: 2019-02-28

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of cardiac resynchronization therapy, device treatment is sufficient and neurohumoral blocker therapy can safely be withdrawn

Conditions

Heart Failure (HF)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

non-intervention arm

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)

Group Type: NO_INTERVENTION

No interventions assigned to this group

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

Group Type: ACTIVE_COMPARATOR

beta blockers

Intervention Type: 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

Group Type: ACTIVE_COMPARATOR

RAAS blockers

Intervention Type: DRUG

RAAS blockers (combination of ACE-I/ARB and a mineralocorticoid receptor antagonist)

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

Group Type: ACTIVE_COMPARATOR

beta blockers

Intervention Type: DRUG

RAAS blockers

Intervention Type: DRUG

RAAS blockers (combination of ACE-I/ARB and a mineralocorticoid receptor antagonist)

Interventions

beta blockers

Intervention Type: DRUG

RAAS blockers

RAAS blockers (combination of ACE-I/ARB and a mineralocorticoid receptor antagonist)

Intervention Type: DRUG

Eligibility Criteria

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%)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ziekenhuis Oost-Limburg

OTHER

Sponsor Role: collaborator

Hasselt University

OTHER

Sponsor Role: lead

Responsible Party

Wilfried Mullens, MD PhD

MD PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Petra Nijst, MD

Role: PRINCIPAL_INVESTIGATOR

Ziekenhuis Oost-Limburg

Locations

Ziekenhuis Oost Limburg

Genk, Limburg, Belgium

Countries

Belgium

References

Nijst P, Martens P, Dauw J, Tang WHW, Bertrand PB, Penders J, Bruckers L, Voros G, Willems R, Vandervoort PM, Dupont M, Mullens W. Withdrawal of Neurohumoral Blockade After Cardiac Resynchronization Therapy. J Am Coll Cardiol. 2020 Mar 31;75(12):1426-1438. doi: 10.1016/j.jacc.2020.01.040.

Reference Type: DERIVED

PMID: 32216911 (View on PubMed)

Other Identifiers

ZOL-STOP-CRT

Identifier Type: -

Identifier Source: org_study_id