Withdrawal of Pharmacological Treatment in Patients Responding to Cardiac Resynchronization Therapy:

Study Overview
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Brief Summary
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The purpose of this randomized trial is to investigate the effect of the complete removal of pharmacological treatment in patients responding to cardiac resynchronization therapy with recuperated LVEF in terms of imaging parameters (changes in LVEF and LV volume), as well as, clinical parameters that translate into worsening of heart failure.

Official Title
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Withdrawal of Pharmacological Treatment in Patients Responding to Cardiac Resynchronization Therapy: Open and Randomized Study

Conditions
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Heart Failure

Intervention / Treatment
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* Other: Complete removal of pharmacological treatment
* Drug: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with a CRT device for at least one year due to the presence of LBBB and LVEF <40% of non-ischemic origin Current LVEF ≥50% and normal volumes in two consecutive echocardiographic studies, separated at least 3 months, and the last one performed in the previous 6 months. Normally functioning CRT device with stimulation> 95%. NYHA functional class I-II. Absence of admissions for HF in the last year. NT-proBNP <450pg/ml in sinus rhythm and <900pg/ml in patients with atrial fibrillation, in the previous 6 months. Pharmacological treatment with beta-blockers, ACEIs/AIIRA/RNAI with or without MRA. Older than 18 years. Patients who have given their informed consent in writing. Exclusion Criteria: Previous episode of sustained ventricular tachycardia/recovered sudden death/appropriate shock (in the case of a patient with an implantable cardioverter-defibrillator associated with CRT). Uncontrolled arterial hypertension (figures> 140/90 mmHg). Need to use beta-blockers at the medical discretion for other indications such as heart rate (HR) control in atrial fibrillation (in the absence of ablation of the atrioventricular node) or to control other supra or ventricular arrhythmias. Severe valve disease. Diabetic or hypertensive with microalbuminuria or proteinuria. Renal failure with creatinine clearance <30ml/min/1.73m2. Fertile women who are neither using contraceptives nor surgically sterilized; pregnant or lactating women. Patients are currently participating in a clinical trial or have participated in the past 30 days.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>Complete removal of pharmacological treatment | Other: Complete removal of pharmacological treatment<br>* Removal of treatment<br>|
| Active Comparator: Control<br>Maintenance of pharmacological treatment | Drug: Control<br>* Maintenance of pharmacological treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. A reduction in LVEF (Left ventricular ejection fraction) of more than 10% | Number of patients with echocardiographic studies | Up to 48 weeks | 
| 2. An increase >15% in the VTSVIi (The end-systolic volume of the indexed left ventricle) to the previous one and in a range higher than the normal value | Number of patients with echocardiographic studies | Up to 48 weeks | 
| 3. Clinical evidence of HF (Heart Failure) based on a global assessment, both clinical and analytical, together with the need to increase the dose of diuretics, as adjudicated by the research team. | Number of patients with echocardiographic studies | Up to 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| total mortality, (Number ) | Total Number | Up to 48 weeks | 
| Cardiovascular mortality, | Total Number | Up to 48 weeks | 
| Unplanned hospital admission or emergency room visit for HF (Heart Failure) | Total Number | Up to 48 weeks | 
| Unplanned hospital admission or emergency room visit for sustained atrial or ventricular arrhythmias (>30 seconds). | Total Number | Up to 48 weeks | 
| Changes with respect to baseline levels of BP (Blood pressure ) |  | Up to 48 weeks | 
| Changes with respect to baseline levels of HR figures. (heart rate) |  | Up to 48 weeks | 
| Change from baseline LVEF |  | Up to 48 weeks | 
| Change from baseline left ventricular end-diastolic volume (VTDVIi) |  | Up to 48 weeks | 
| Change from baseline body surface indexed left atrium volume (VAIi) |  | Up to 48 weeks | 
| Changes from baseline in global longitudinal strain (GLS).GLS is a simple parameter that expresses longitudinal shortening as a percentage (change in length as a proportion to baseline length). |  | Up to 48 weeks | 
| Changes in the quality of life questionnaires according to The Minnesota Living with Heart Failure (MLHFQ) scales. | The response options range from 0, which indicates unaffected HRQL, to 5, which indicates the maximum impact on HRQL. | Up to 48 weeks | 
| Changes in the quality of life questionnaires according to The Kansas City Cardiomyopathy Questionnaire (KCCQ) scales. | The KCCQ is a 23-item (15 question) self-administered questionnaire designed to quantify physical limitations, symptoms (frequency, severity and recent change over time), social limitations, self-efficacy, and quality of life.As described, all KCCQ scores are scaled from 0 to 100 and frequently summarized in 25-point ranges, where scores represent health status as follows: 0 to 24: very poor to poor; 25 to 49: poor to fair; 50 to 74: fair to good; and 75 to 100: good to excellent. | Up to 48 weeks |