Withdrawal of Heart Failure Treatment Patients With Non-ischemic Cardiomyopathy Who Have Been Super-responders to Cardiac Resynchronization Therapy. (DRUGLESS-CRT)

Withdrawal of Heart Failure Treatment in Patients With Non-ischemic Cardiomyopathy, Without Late Gadolinium Enhancement and With a Negative Genetic Test, Who Have Been Super-responders to Cardiac Resynchronization Therapy.

Multicenter, prospective, non-inferiority, randomized, single-blind (primary endpoint evaluators blinded, patients not blinded) clinical trial.

We aim to evaluate if the withdrawal of heart failure treatment is safe in patients with non-ischemic cardiomyopathy, negative genetic test, no evidence of late gadolinium enhancement on cardiac MRI, who have been super-responders to cardiac resynchronization therapy and remain free of heart failure events for at least 6 months after device implantation.

Study Overview

• Status: Recruiting
• Conditions: Non-ischemic Cardiomyopathy; Cardiac Resynchronisation Therapy (CRT)
• Intervention / Treatment: Drug: Withdrawal of Heart failure medications

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Andrea Di Marco, MD, PhD; Phone Number: +34932607686; Email: adimarco@bellvitgehospital.cat

Study Locations

• Spain
  • Barcelona, Spain
    • Recruiting
    • Hospital Vall d'Hebron
    • Contact: Jaume Francisco Pascual; Phone Number: +34932607686; Email: adimarco@bellvitgehospital.cat
  • Girona, Spain
    • Recruiting
    • Hospital Trueta
    • Contact: Carles Moliner; Phone Number: +34932607686; Email: adimarco@bellvitgehospital.cat
  • Granada, Spain
    • Recruiting
    • Hospital Virgen de las Nieves
    • Contact: Laura Jordan; Phone Number: +34932607686; Email: adimarco@bellvitgehospital.cat
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Recruiting
      • Hospital Universitari de Bellvitge
      • Contact: Andrea Di Marco; Phone Number: +34932607686; Email: adimarco@bellvitgehospital.cat

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:

• Diagnosis of non-ischemic cardiomyopathy
• LBBB already present at the time of first diagnosis of LV dysfunction
• Negative genetic test
• Cardiac MRI with no evidence of late gadolinium enhancement (LGE at RV insertion points is acceptable)
• Carrier of a resynchronization device (ICD or pacemaker, with LV epicardial pacing form a cardiac vein or left bundle area pacing), pacing percentage >95% and paced QRS <140 ms
• Device indication: LVEF ≤35% and LBBB with QRS >150 ms
• LVEF ≥50% and normal indexed LV volumes on echocardiogram performed at least 6 months after CRT implantation
• No heart failure decompensations (no hospitalizations or urgent/day hospital visits) since CRT implantation
• No need for loop diuretic treatment
• NYHA class I or II
• NT-proBNP <450 ng/L (or <1000 ng/L in atrial fibrillation/flutter)
• On neurohormonal therapy with at least two drugs

Exclusion Criteria:

• Family history of non-ischemic cardiomyopathy with LVEF <50% in at least one first-degree relative
• Severe valvular heart disease
• History of sustained ventricular arrhythmia or treated by ICD
• Need to maintain beta-blocker therapy for other arrhythmias
• Hypertension not controlled with other medications
• CRT devices implanted as an upgrade from prior pacemaker or ICD, where prior pacing percentage was >20%
• Clinical indication other than heart failure to maintain any of the neurohormonal treatment drugs (class I recommendation in ESC or ACC/AHA guidelines)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control Group; Continue heart failure medical tretment without changes
Active Comparator: Drugs withdrawal group; Heart failure medications are progressively withdrawn, in a máximum period of 9 weeks, always with the same protocol in every patient.	Drug: Withdrawal of Heart failure medications; Heart failure drugs will be withdrawn progressively over a maximum of 9 weeks, discontinuing drugs one by one following a predefined sequence

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence of left ventricular dysfunction or heart failure symptoms at 6 months	Any of the following events: Decrease in LVEF >10% and final LVEF <50%; Decrease in LVEF >10% and increase in LV end-systolic volume >15%; Appearance of heart failure symptoms accompanied by elevated NT-proBNP requiring initiation of oral, subcutaneous, or intravenous loop diuretic treatment.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Emergency room or day hospital visits for heart failure		6 and 12 months
Hospitalizations due to heart failure		6 and 12 months
Ventricular arrhythmias	Sustained ventricular tachycardia, sudden cardiac death, appropriate ICD therapy	6 and 12 months
Supraventricular arrhythmias	Sustained supraventricular arrhythmia, including sustained atrial fibrillation, sustained atrial flutter and sustained atrial tachycardia	6 and 12 months
NYHA class	New York Heart Association functional class, limits I-IV, higher scores means worse outcome	6 and 12 months
NtproBNP	levels of NTproBNP, as measured in blood sample	6 and 12 months
Quality of life, assessed with KCCQ	KCCQ: Kansas City Cardiomyopathy Questionnaire, minimum and maximum values 0-100, higher scores indicate better outcome	6 and 12 months
Quality of life as evaluated with the EQ-5D-5L, EQ VAS	EuroQol five-dimension, five-level questionnaire - visual analogue scale, minimum and maximum value 0-100, higher score indicates better outcome	6 months and 12 months
Quality of life evaluated with the EQ-5D-5L-index value	EuroQol five-dimension, five-level questionnaire - index value, minimum and maximum value 0-1, higher score indicates better outcome	6 months and 12 months

Collaborators and Investigators

• Sponsor: Institut d'Investigació Biomèdica de Bellvitge
• Collaborators: Hospital Universitari de Bellvitge; Hospital Universitario La Paz; Hospital Vall d'Hebron; Hospital de Sant Pau; University Hospital Virgen de las Nieves

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2026
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: February 4, 2026
• First Submitted That Met QC Criteria: September 25, 2026
• First Posted (Actual): October 1, 2026

Study Record Updates

• Last Update Posted (Actual): October 1, 2026
• Last Update Submitted That Met QC Criteria: September 25, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Cardiac resynchronization therapy; Non-ischemic cardiomyopathy; Late gadolinium enhancement; Cardiogenetic; Heart failure medical treatment
• Other Study ID Numbers: DRUGLESS-CRT; 2025 (U.S. NIH Grant/Contract); 2025-521780-12-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No