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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure
• Intervention / Treatment: Other: Complete removal of pharmacological treatment; Drug: Control

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Francisco José Pastor Pérez, MD; Phone Number: 968369500; Email: franpastor79@hotmail.com
• Study Contact Backup: Name: Lola Serna Guirao; Email: lola.serna@carm.es

Study Locations

• Spain
  • Murcia, Spain, 30120
    • Recruiting
    • Hospital Clínico Universitario Virgen de la Arrixaca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient with a CRT device for at least one year due to the presence of LBBB and LVEF <40% of non-ischemic origin
2. 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.
3. Normally functioning CRT device with stimulation> 95%.
4. NYHA functional class I-II.
5. Absence of admissions for HF in the last year.
6. NT-proBNP <450pg/ml in sinus rhythm and <900pg/ml in patients with atrial fibrillation, in the previous 6 months.
7. Pharmacological treatment with beta-blockers, ACEIs/AIIRA/RNAI with or without MRA.
8. Older than 18 years.
9. Patients who have given their informed consent in writing.

Exclusion Criteria:

1. 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).
2. Uncontrolled arterial hypertension (figures> 140/90 mmHg).
3. 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.
4. Severe valve disease.
5. Diabetic or hypertensive with microalbuminuria or proteinuria.
6. Renal failure with creatinine clearance <30ml/min/1.73m2.
7. Fertile women who are neither using contraceptives nor surgically sterilized; pregnant or lactating women.
8. Patients are currently participating in a clinical trial or have participated in the past 30 days.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; Complete removal of pharmacological treatment	Other: Complete removal of pharmacological treatment; Removal of treatment
Active Comparator: Control; Maintenance of pharmacological treatment	Drug: Control; Maintenance of pharmacological treatment

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia
• Investigators: Principal Investigator: Francisco José Pastor Pérez, MD, HCUVA

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2021
• Primary Completion (Anticipated): November 15, 2022
• Study Completion (Anticipated): May 15, 2023

Study Registration Dates

• First Submitted: November 12, 2021
• First Submitted That Met QC Criteria: November 26, 2021
• First Posted (Actual): December 9, 2021

Study Record Updates

• Last Update Posted (Actual): December 30, 2021
• Last Update Submitted That Met QC Criteria: December 9, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: IMIB-RMV-2021-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No