Withdrawal of neurohormonal therapy in patients with non-ischemic cardiomyopathy, no late gadolinium enhancement, and negative genetic testing, who have exhibited super-response to cardiac resynchronization therapy. DRUGLESS-CRT clinical trial.

2025-521780-12-00 Protocol DRUGLESS-CRT Phase III and Phase IV (Integrated) Authorised, recruiting

Start 16 Dec 2025 · Status Authorised, recruiting · 1 EU/EEA countries · 6 sites · Protocol DRUGLESS-CRT

Overview

Sponsor-declared trial summary

Phase Phase III and Phase IV (Integrated)
Status Authorised, recruiting
Participants planned 64
Countries 1
Sites 6

Non-ischemic cardiomyopathy

Demonstrate that the withdrawal of neurohormonal treatment is not inferior to its maintenance in terms of recurrence of left ventricular dysfunction or heart failure symptoms, in patients with non-ischemic cardiomyopathy, without significant arrhythmia, with negative genetic testing who have been super-responders to ca…

Key facts

Sponsor
Andrea Di Marco
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Cardiovascular Diseases [C14]
Trial duration
16 Dec 2025 → ongoing
Decision date (initial)
2025-10-28
Transition trial
No
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Demonstrate that the withdrawal of neurohormonal treatment is not inferior to its maintenance in terms of recurrence of left ventricular dysfunction or heart failure symptoms, in patients with non-ischemic cardiomyopathy, without significant arrhythmia, with negative genetic testing who have been super-responders to cardiac resynchronization therapy

Secondary objectives 1

  1. Demonstrate that the withdrawal of neurohormonal treatment is not inferior to its maintenance in terms of hospital admissions for heart failure, occurrence of ventricular or supraventricular arrhythmias, NT-proBNP levels, NYHA class, and quality of life.

Conditions and MedDRA coding

Non-ischemic cardiomyopathy

VersionLevelCodeTermSystem organ class
20.0 LLT 10055222 Non-ischemic cardiomyopathy 10007541

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

  1. Age >18 years
  2. Diagnosis of non-ischemic cardiomyopathy
  3. Negative genetic test (at least 50 genes evaluated)
  4. Cardiac magnetic resonance imaging without evidence of late gadolinium enhancement (RTG is accepted at the insertion points of the right ventricle).
  5. Carrier of a resynchronization device (ICD or pacemaker, biventricular stimulation or left branch area stimulation) with >95% pacing and stimulated QRS <140ms.
  6. Indication for resynchronization device: LVEF ≤35% and LBBB with QRS >150ms
  7. LVEF ≥50% and normal indexed left ventricular volumes on echocardiogram performed at least 6 months after the resynchronization device implantation.
  8. No heart failure decompensations (no hospital admissions, no emergency visits, or day care hospital visits) since the implantation of the resynchronization device.
  9. No need for loop diuretic treatment.
  10. NYHA Class I or II
  11. NT-proBNP <450 ng/L (or <1000 ng/L if atrial fibrillation or atrial flutter)
  12. Neurohormonal treatment with at least two medications

Exclusion criteria 5

  1. Severe valvulopathy
  2. History of sustained ventricular arrhythmia or treated by ICD
  3. Need to maintain beta-blocker therapy for other arrhythmias
  4. Hypertension that cannot be controlled with other medications
  5. Resynchronization devices implanted as an upgrade from previous pacemaker or ICD, where the pacing percentage before the upgrade was >20%.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Recurrence of left ventricular dysfunction or heart failure at 6 months (any of the following events): Decrease in LVEF >10% and LVEF <50% or; decrease in LVEF >10% and an increase in the left ventricular end-systolic volume >15% or; onset of heart failure symptoms accompanied by an elevation in NT-proBNP requiring initiation of treatment with oral, subcutaneous, or intravenous loop diuretic therapy.

Secondary endpoints 8

  1. Emergency or day care hospital visits for heart failure at 6 and 12 months
  2. Hospital admissions for heart failure at 6 and 12 months
  3. Ventricular arrhythmias at 6 and 12 months
  4. Supraventricular arrhythmias at 6 and 12 months
  5. NT-proBNP levels at 6 and 12 months
  6. NYHA class at 6 and 12 months
  7. Quality of life at 6 and 12 months
  8. Recurrence of left ventricular dysfunction or heart failure (as defined for the primary endpoint) at 12 months.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 20

Perindopril Tert-Butylamine

SCP126600 · ATC

Active substance
Perindopril Tert-Butylamine
Substance synonyms
PERINDOPRIL ERBUMINE
Route of administration
ORAL
Max daily dose
50 mg milligram(s)
Max total dose
50 mg milligram(s)
Max treatment duration
9 Week(s)
Authorisation status
Authorised
ATC code
C07AG02 — CARVEDILOL
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Nebivolol

SCP1150567 · ATC

Active substance
Nebivolol
Route of administration
ORAL
Max daily dose
10 mg milligram(s)
Max total dose
10 mg milligram(s)
Max treatment duration
9 Week(s)
Authorisation status
Authorised
ATC code
C07AB12 — NEBIVOLOL
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Cinnarizine

SCP111868187 · ATC

Active substance
Cinnarizine
Substance synonyms
CINARIZINE
Route of administration
ORAL
Max daily dose
50 mg milligram(s)
Max total dose
50 mg milligram(s)
Max treatment duration
9 Week(s)
Authorisation status
Authorised
ATC code
C03DA01 — SPIRONOLACTONE
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Altizide

SCP172422 · ATC

Active substance
Altizide
Substance synonyms
ALTHIAZIDE
Route of administration
ORAL
Max daily dose
50 mg milligram(s)
Max total dose
50 mg milligram(s)
Max treatment duration
9 Week(s)
Authorisation status
Authorised
ATC code
C03DA04 — EPLERENONE
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Dapagliflozin Propanediol

SCP100377942 · ATC

Active substance
Dapagliflozin Propanediol
Route of administration
ORAL
Max daily dose
10
Max total dose
10
Max treatment duration
9 Week(s)
Authorisation status
Authorised
ATC code
A10BK01 — DAPAGLIFLOZIN
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Captopril

SCP128193 · ATC

Active substance
Captopril
Route of administration
ORAL
Max daily dose
150 mg milligram(s)
Max total dose
150 mg milligram(s)
Max treatment duration
9 Week(s)
Authorisation status
Authorised
ATC code
C09AA01 — CAPTOPRIL
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Lisinopril Dihydrate

SCP1138921 · ATC

Active substance
Lisinopril Dihydrate
Route of administration
ORAL
Max daily dose
40 mg milligram(s)
Max total dose
40 mg milligram(s)
Max treatment duration
9 Week(s)
Authorisation status
Authorised
ATC code
C09AA03 — LISINOPRIL
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Losartan Potassium

SCP1083046 · ATC

Active substance
Losartan Potassium
Route of administration
ORAL
Max daily dose
100 mg milligram(s)
Max total dose
100 mg milligram(s)
Max treatment duration
9 Week(s)
Authorisation status
Authorised
ATC code
C09CA01 — LOSARTAN
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Valsartan

SCP121869466 · ATC

Active substance
Valsartan
Route of administration
ORAL
Max daily dose
194 mg milligram(s)
Max total dose
194 mg milligram(s)
Max treatment duration
9 Week(s)
Authorisation status
Authorised
ATC code
C09DX04 — VALSARTAN AND SACUBITRIL
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Enalapril Maleate

SCP129505 · ATC

Active substance
Enalapril Maleate
Substance synonyms
Enalapril hydrogen maleate
Route of administration
ORAL
Max daily dose
40 mg milligram(s)
Max total dose
40 mg milligram(s)
Max treatment duration
9 Week(s)
Authorisation status
Authorised
ATC code
C09AA02 — ENALAPRIL
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Hydrochlorothiazide

SCP10361725 · ATC

Active substance
Hydrochlorothiazide
Route of administration
ORAL
Max daily dose
10 mg milligram(s)
Max total dose
10 mg milligram(s)
Max treatment duration
9 Week(s)
Authorisation status
Authorised
ATC code
C09AA05 — RAMIPRIL
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Candesartan

SCP128457 · ATC

Active substance
Candesartan
Route of administration
ORAL
Max daily dose
32 mg milligram(s)
Max total dose
32 mg milligram(s)
Max treatment duration
9 Week(s)
Authorisation status
Authorised
ATC code
C09CA06 — CANDESARTAN
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Atenolol

SCP1160479 · ATC

Active substance
Atenolol
Substance synonyms
2-[4-[2-HYDROXY-3-(PROPAN-2-YLAMINO)PROPOXY]PHENYL]ACETAMIDE
Route of administration
ORAL
Max daily dose
100 mg milligram(s)
Max total dose
100 mg milligram(s)
Max treatment duration
9 Week(s)
Authorisation status
Authorised
ATC code
C07AB03 — ATENOLOL
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Propranolol Hydrochloride

SCP129860 · ATC

Active substance
Propranolol Hydrochloride
Substance synonyms
PROPRANOLOLI HYDROCHLORIDUM, PROPRANOLOL HYDROCHLORIIDE, 1-NAPHTHALEN-1-YLOXY-3-(PROPAN-2-YLAMINO)PROPAN-2-OL HYDROCHLORIDE
Route of administration
ORAL USE
Max daily dose
160 mg milligram(s)
Max total dose
160 mg milligram(s)
Max treatment duration
9 Week(s)
Authorisation status
Authorised
ATC code
C07AA05 — PROPRANOLOL
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Metoprolol Succinate

SCP1159601 · ATC

Active substance
Metoprolol Succinate
Substance synonyms
BUTANEDIOIC ACID, 1-[4-(2-METHOXYETHYL)PHENOXY]-3-(PROPAN-2-YLAMINO)PROPAN-2-OL
Route of administration
ORAL
Max daily dose
20 mg milligram(s)
Max total dose
20 mg milligram(s)
Max treatment duration
9 Week(s)
Authorisation status
Authorised
ATC code
C07AB02 — METOPROLOL
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Bisoprolol Fumarate

SCP109534428 · ATC

Active substance
Bisoprolol Fumarate
Route of administration
ORAL
Max daily dose
10 mg milligram(s)
Max total dose
10 mg milligram(s)
Max treatment duration
9 Week(s)
Authorisation status
Authorised
ATC code
C07AB07 — BISOPROLOL
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Valsartan

SCP1000156 · ATC

Active substance
Valsartan
Route of administration
ORAL
Max daily dose
320 mg milligram(s)
Max total dose
320 mg milligram(s)
Max treatment duration
9 Week(s)
Authorisation status
Authorised
ATC code
C09CA03 — VALSARTAN
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Hydrochlorothiazide

SCP136623 · ATC

Active substance
Hydrochlorothiazide
Route of administration
ORAL
Max daily dose
80 mg milligram(s)
Max total dose
80 mg milligram(s)
Max treatment duration
9 Week(s)
Authorisation status
Authorised
ATC code
C09CA07 — TELMISARTAN
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Valsartan

SCP131775 · ATC

Active substance
Valsartan
Route of administration
ORAL
Max daily dose
300 mg milligram(s)
Max total dose
300 mg milligram(s)
Max treatment duration
9 Week(s)
Authorisation status
Authorised
ATC code
C09CA04 — IRBESARTAN
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Empagliflozin

SCP274024 · ATC

Active substance
Empagliflozin
Route of administration
ORAL
Max daily dose
25
Max total dose
25
Max treatment duration
9 Week(s)
Authorisation status
Authorised
ATC code
A10BK03 — EMPAGLIFLOZIN
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Andrea Di Marco

Sponsor organisation
Andrea Di Marco
Address
Carrer De La Feixa Llarga S/n, L Hospitalet De Llobregat L Hospitalet De Llobregat
City
Barcelona
Postcode
08907
Country
Spain

Scientific contact point

Organisation
Andrea Di Marco
Contact name
Andrea Di Marco

Public contact point

Organisation
Andrea Di Marco
Contact name
Andrea Di Marco

Third parties 1

OrganisationCity, countryDuties
Galaxia Empirica S.L.
ORG-100047280
 Moana, Spain Code 12

Locations

1 EU/EEA country · 6 investigational sites

By country

CountryMS statusPlanned subjectsSites
Spain Authorised, recruiting 64 6
Rest of world — 0 —

Investigational sites

Spain

6 sites · Authorised, recruiting
Hospital Universitari Vall D Hebron
Cardiology, Passeig De La Vall D'Hebron 119-129, 08035, Barcelona
Hospital Universitario Virgen De Las Nieves
Cardiology, Avenida De Las Fuerzas Armadas 2, 18014, Granada
Hospital Universitario La Paz
Cardiology, Paseo De La Castellana 261, 28046, Madrid
Hospital Universitari De Girona Doctor Josep Trueta
Cardiology, Avinguda De Franca S/n, 17007, Girona
Hospital De La Santa Creu I Sant Pau
Cardiology, Calle De San Antonio Maria Claret 167, 08025, Barcelona
Bellvitge University Hospital
Cardiology, Carrer De La Feixa Llarga S/N, 08907, L'Hospitalet De Llobregat

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Spain 2025-12-16

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 24 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) DRUGLESS CRT V1 1 1.1
Protocol (for publication) DRUGLESS CRT V1 2 1.2
Recruitment arrangements (for publication) K1_Recruitment arrangements 1
Subject information and informed consent form (for publication) L1_SIS and ICF general 1
Summary of Product Characteristics (SmPC) (for publication) Atenolol 1
Summary of Product Characteristics (SmPC) (for publication) Bisoprolol 1
Summary of Product Characteristics (SmPC) (for publication) Candesartan 1
Summary of Product Characteristics (SmPC) (for publication) Captopril 1
Summary of Product Characteristics (SmPC) (for publication) Carvedilol 1
Summary of Product Characteristics (SmPC) (for publication) Dapagliflozina 1
Summary of Product Characteristics (SmPC) (for publication) Empagliflozina 1
Summary of Product Characteristics (SmPC) (for publication) Enalapril 1
Summary of Product Characteristics (SmPC) (for publication) Eplerenona 1
Summary of Product Characteristics (SmPC) (for publication) Espironolactona 1
Summary of Product Characteristics (SmPC) (for publication) Irbesartan 1
Summary of Product Characteristics (SmPC) (for publication) Lisinopril 1
Summary of Product Characteristics (SmPC) (for publication) Losartan 1
Summary of Product Characteristics (SmPC) (for publication) Metoprolol 1
Summary of Product Characteristics (SmPC) (for publication) Nebivolol 1
Summary of Product Characteristics (SmPC) (for publication) Propanolol 1
Summary of Product Characteristics (SmPC) (for publication) Ramipril 1
Summary of Product Characteristics (SmPC) (for publication) SacubitrilValsartan 1
Summary of Product Characteristics (SmPC) (for publication) Telmisartan 1
Summary of Product Characteristics (SmPC) (for publication) Valsartan 1

Application history

2 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2025-05-13 Spain Acceptable with conditions
2025-08-11
 2025-10-28
2 SUBSTANTIAL MODIFICATION SM-1 2025-10-28 Spain Acceptable
2025-12-03
 2025-12-05

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