Clinical trial NCT02200822: Systematic Withdrawal of Neurohumoral Blocker Therapy in Optimally Responding CRT Patients
Official title: Systematic Withdrawal of Neurohumoral Blocker Therapy in Optimally Responding Patients to Cardiac Resynchronization Therapy: the STOP-CRT Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Heart Failure (HF)
Keywords: neurohumoral blocker therapy
renin-angiotensin-aldosterone system (RAAS)
RAAS-blocker
beta blocker
spironolactone
angiotensin converting enzyme inhibitor (ACE-I)
angiotensin receptor blocker (ARB)
cardiac resynchronization therapy (CRT)
heart failure
dyssynchrony
left bundle branch block
Lead sponsor: Hasselt University
Sponsor class: OTHER
Collaborators: name: Ziekenhuis Oost-Limburg
First posted: 2014-07-25
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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of cardiac resynchronization therapy, device treatment is sufficient and neurohumoral blocker therapy can safely be withdrawn


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%)

Primary outcomes:
measure: a > 15% increase in left ventricular end systolic volume
timeFrame: at 12 months
Secondary outcomes:
measure: - Incidence of HF related hospitalizations defined as admission to hospital / presentation to emergency room with need for parental therapy
timeFrame: at 12 months
measure: All cause mortality
timeFrame: at 12 months
measure: VO2 max change
timeFrame: at 12 months
Other outcomes:
measure: >15% increase in left ventricular end systolic volume
timeFrame: 6 and 24 months
measure: > 15% decrease in left ventricular ejection fraction
timeFrame: at 6, 12 and 24 months
measure: mean blood pressure change
timeFrame: at 6, 12 and 24 months
measure: HF symptoms change (dyspnea visual analogue scale (VAS), New York Heart Association (NYHA) class, questionnaire "Minnesota living with Heart Failure")
timeFrame: at 6, 12 and 24 months
measure: incidence of heart rhythm events (sustained ventricular tachycardia (VT), atrial fibrillation, ventricular fibrillation)
timeFrame: at 6, 12 and 24 months
measure: heart rate variability
timeFrame: at 6, 12 and 24 months
measure: urinary catecholamine concentration
timeFrame: at 6, 12 and 24 months
measure: change in myocardial contractility (force frequence relationship, left ventricular pre-ejection time, iso-volumetric contraction time, dP/dt)
timeFrame: at 6, 12 and 24 months
measure: change in diastolic filling pattern
timeFrame: at 6, 12 and 24 months
measure: plasma concentrations of plasma renin activity and aldosterone
timeFrame: at 6, 12 and 24 months
Locations:
city: Genk
country: Belgium
facility: Ziekenhuis Oost Limburg
state: Limburg
Study officials:
affiliation: Ziekenhuis Oost-Limburg
name: Petra Nijst, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.