Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Ongoing, recruitment ended
Participants planned
60
Countries
1
Sites
9
Heart Failure
To determine the effect of withdrawing pharmacologic treatment in patients with cardiac resynchronization therapy with recovered LVEF, in terms of both imaging parameters (changes in LVEF and LV volume) as well as clinical parameters that reflect worsening of the heart failure.
Key facts
- Sponsor
- Fundacion Para La Formacion E Investigacion Sanitaria De La Region De Murcia
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Cardiovascular Diseases [C14]
- Trial duration
- 1 Dec 2021 → ongoing
- Decision date (initial)
- 2023-04-24
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
External identifiers
- EU CT number
- 2023-504946-70-00
- EudraCT number
- 2021-001327-41
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Others
To determine the effect of withdrawing pharmacologic treatment in patients with cardiac resynchronization therapy with recovered LVEF, in terms of both imaging parameters (changes in LVEF
and LV volume) as well as clinical parameters that reflect worsening of the heart failure.
Secondary objectives 3
- To determine the safety of withdrawing drug treatment in patients undergoing cardiac resynchronization therapy with recovered LVEF, in terms of adverse events during follow-up, including total death, cardiovascular death, hospital admission or emergency room visit for HF, and sustained (>30 seconds) supraventricular or ventricular arrhythmias.
- The determination of changes in other echocardiographic measures as well as in the levels of natriuretic peptides, vital signs and scores in the quality of life tests.
- Influence of cardiomyopathy genotype on the response to medication withdrawal.
Conditions and MedDRA coding
Heart Failure
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | LLT | 10019279 | Heart failure | 10007541 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 9
- Patients who have received cardiac resynchronization therapy at least one year before for left bundle branch block and LVEF <40% of non-ischemic origin.
- Current LVEF ≥ 50% and normal volumes in two studies consecutive echocardiograms, separated by at least 3 months, with the last performed in the previous six months.
- NYHA functional class I-II
- Absence of admissions for heart failure in the last year
- NT-proBNP <450 pg/mL in patients in sinus rhythm or <900 pg/mL in patients with atrial fibrillation, in the previous 6 months.
- Pharmacological treatment with beta-blockers, ACEIs/ARA II/ARNI with or without ARM
- Normally functioning cardiac resynchronization therapy device with >95% pacing
- Older than 18 years
- Patients who have given their written informed consent.
Exclusion criteria 8
- Previous episode of sustained ventricular tachycardia/sudden death recovered/appropriate discharge (in case of being a carrier of implantable cardioverter-defibrillator associated with cardiac resynchronization therapy)
- Uncontrolled arterial hypertension (figures >140/90 mmHg).
- Need for the use of beta-blockers at the medical discretion of 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.
- Diabetics or hypertensives with microalbuminuria or proteinuria
- Renal failure with creatinine clearance < 30 ml/min/1.73m2.
- Fertile women who do not use contraception or are sterilizedsurgically; pregnant or lactating women.
- Currently participating in a clinical trial or have participated in the previous 30 days
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Relapse of cardiomyopathy at any time during the study after drug withdrawal, defined by at least one of the following: 1. A reduction in LVEF of more than 10% (as long as the overall LVEF is < 50%). 2. A reduction in LVEF of more than 10% accompanied by a >15% increase in left ventricular end-systolic volume. 3. Unplanned hospital admission or visit to the Emergency Department/day hospital due to decompensated HF requiring the administration of intravenous diuretics.
Secondary endpoints 5
- Combined total mortality, cardiovascular mortality, hospital admission or visit to the Emergency Department/unplanned day hospital for HF, and sustained atrial or ventricular arrhythmias (>30 seconds).
- Changes with respect to the basal levels of BP and HR.
- Change from baseline in LVEF, LVTVV, left atrial volume indexed by body surface area (VAIi), and changes from baseline in left ventricular (LV) longitudinal global strain (LSG).
- Quantitative changes in NT-proBNP numbers.
- Changes in the quality of life questionnaires according to The Kansas City Cardiomyopathy Questionnaire (KCCQ) and Minnesota Living With Heart Failure (MLHFQ) scale.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 10
eplerenona cinfa 50 mg comprimidos recubiertos con película EFG
PRD683637 · Product
- Active substance
- Eplerenone
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 50 mg milligram(s)
- Max total dose
- 50 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- C03DA04 — -
- Marketing authorisation
- 76.245
- MA holder
- LABORATORIOS CINFA, S.A.
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Bisoprolol Cor Aristo 2,5 mg comprimidos recubiertos con película EFG
PRD6326210 · Product
- Active substance
- Bisoprolol Fumarate
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- C07AB07 — BISOPROLOL
- Marketing authorisation
- 75.892
- MA holder
- ARISTO PHARMA GMBH (ART 57)
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Diován Cardio 40 mg comprimidos recubiertos con película
PRD476762 · Product
- Active substance
- Valsartan
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 320 mg milligram(s)
- Max total dose
- 320 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- C09CA03 — VALSARTAN
- Marketing authorisation
- 66.910
- MA holder
- NOVARTIS FARMACÉUTICA S.A.
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Furosemida KERN PHARMA 40 mg comprimidos EFG
PRD375645 · Product
- Active substance
- Furosemide
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 80 mg milligram(s)
- Max total dose
- 80 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- C03CA01 — FUROSEMIDE
- Marketing authorisation
- 69.620
- MA holder
- KERN PHARMA, S.L.
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Diován 80 mg comprimidos recubiertos con película
PRD476744 · Product
- Active substance
- Valsartan
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 320 mg milligram(s)
- Max total dose
- 320 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- C09CA03 — VALSARTAN
- Marketing authorisation
- 64.454
- MA holder
- NOVARTIS FARMACÉUTICA S.A.
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Bisoprolol Cor Aristo 5 mg comprimidos recubiertos con película EFG
PRD6326211 · Product
- Active substance
- Bisoprolol Fumarate
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- C07AB07 — BISOPROLOL
- Marketing authorisation
- 75.893
- MA holder
- ARISTO PHARMA GMBH (ART 57)
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Bisoprolol Cor Aristo 10 mg comprimidos recubiertos con película EFG
PRD6326212 · Product
- Active substance
- Bisoprolol Fumarate
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- C07AB07 — BISOPROLOL
- Marketing authorisation
- 75.894
- MA holder
- ARISTO PHARMA GMBH (ART 57)
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Diován 320 mg comprimidos recubiertos con película
PRD476722 · Product
- Active substance
- Valsartan
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 320 mg milligram(s)
- Max total dose
- 320 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- C09CA03 — VALSARTAN
- Marketing authorisation
- 68.817
- MA holder
- NOVARTIS FARMACÉUTICA S.A.
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
eplerenona cinfa 25 mg comprimidos recubiertos con película EFG
PRD683638 · Product
- Active substance
- Eplerenone
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 50 mg milligram(s)
- Max total dose
- 50 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- C03DA04 — -
- Marketing authorisation
- 76.240
- MA holder
- LABORATORIOS CINFA, S.A.
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Diován 160 mg comprimidos recubiertos con película
PRD476699 · Product
- Active substance
- Valsartan
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 320 mg milligram(s)
- Max total dose
- 320 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- C09CA03 — VALSARTAN
- Marketing authorisation
- 64.473
- MA holder
- NOVARTIS FARMACÉUTICA S.A.
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Fundacion Para La Formacion E Investigacion Sanitaria De La Region De Murcia
- Sponsor organisation
- Fundacion Para La Formacion E Investigacion Sanitaria De La Region De Murcia
- Address
- Carretera De Cartagena S/n, El Palmar El Palmar
- City
- Murcia
- Postcode
- 30120
- Country
- Spain
Scientific contact point
- Organisation
- Fundacion Para La Formacion E Investigacion Sanitaria De La Region De Murcia
- Contact name
- Maria
Public contact point
- Organisation
- Fundacion Para La Formacion E Investigacion Sanitaria De La Region De Murcia
- Contact name
- Maria
Locations
1 EU/EEA country · 9 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Spain | Ongoing, recruitment ended | 60 | 9 |
| Rest of world | — | 0 | — |
Investigational sites
Hospital Universitario Severo Ochoa
Cardiología, Avenida Orellana S/n, 28911, Leganes
Hospital Universitario Fundacion Jimenez Diaz
Cardiology Department, Avenida De Los Reyes Catolicos 2, 28040, Madrid
Complexo Hospitalario Universitario De Santiago
Cardiology Department, Calle Choupana Da S/n, 15706, Santiago De Compostela
Hospital Universitari Germans Trias I Pujol
Cardiology Department, Carretera Canyet 1a Planta, 08916, Badalona
Hospital Universitario Y Politecnico La Fe
Cardiology Department, Avenida De Fernando Abril Martorell 106, 46026, Valencia
Hospital Universitario Virgen De La Victoria
Cardiology Department, Calle Del Arroyo Teatinos S N, 29010, Malaga
Hospital Alvaro Cunqueiro
Cardiology Department, Estrada Clara Campoamor No 341, 36312, Vigo
University Clinical Hospital Virgen De La Arrixaca
Cardiology Department, Carretera De Cartagena S/n, El Palmar, Murcia
Hospital Universitario Puerta De Hierro De Majadahonda
Cardiology Department, Calle De Manuel De Falla 1, 28222, Majadahonda
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Spain | 2021-12-01 | 2021-12-03 | 2025-04-15 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-04-10 | Spain | Acceptable 2023-04-24
|
2023-04-24 |
| 2 | SUBSTANTIAL MODIFICATION | SM-2 | 2023-10-09 | Spain | Acceptable | 2023-11-15 |
| 3 | SUBSTANTIAL MODIFICATION | SM-3 | 2024-05-07 | Spain | Acceptable | 2024-05-20 |