Overview
Sponsor-declared trial summary
Heart failure with preserved ejection fraction Secundary mitral valve regurgitation
The main objective of this study is to assess the hemodynamic effects of sacubitril-valsartan in patients with HFpEF and secondary / atrial functional mitral regurgitation (AFMR), using a combination of cardiopulmonary exercise testing and stress echocardiography (referred to as CPETecho). Secondary endpoints include t…
Key facts
- Sponsor
- Ziekenhuis Oost Limburg
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Cardiovascular Diseases [C14]
- Trial duration
- 29 Feb 2024 → 10 Mar 2026
- Decision date (initial)
- 2023-10-11
- Transition trial
- No
- Low-intervention
- Yes
- Rare-disease indication
- No
- Vulnerable population
- No
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
The main objective of this study is to assess the hemodynamic effects of sacubitril-valsartan in patients with HFpEF and secondary / atrial functional mitral regurgitation (AFMR), using a combination of cardiopulmonary exercise testing and stress echocardiography (referred to as CPETecho). Secondary endpoints include the changes in quantitative valve assessment (EROA), quality of life and different CPETecho parameters.
Conditions and MedDRA coding
Heart failure with preserved ejection fraction Secundary mitral valve regurgitation
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 1
- (1) Age > 18 years (2) NYHA class II to IV (3) Written informed consent (4) Left ventricular ejection fraction ≥ 50% (5) Objective evidence of cardiac structural and/or functional abnormalities consistent with the presence of LV diastolic dysfunction/raised LV filling pressures*, including raised natriuretic peptides** (6) ≥ moderate functional MR assessed by TTE within the previous year
Exclusion criteria 1
- (1) Systolic blood pressure < 100 mmHg (2) Potassium ≥ 5.2 mmol/L (3) eGFR ≤ 25 ml/min/1.73m² (4) History of angioedema or unacceptable side effects during receipt of ACE inhibitors or ARBs (5) Structural mitral valve disease and previous or planned mitral valve intervention (6) Already receiving ARNI (sacubitril-valsartan) therapy (7) Severe comorbid condition limiting life expectancy < 24 months or inability to perform a maximal CPETecho
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Change in the mPAP/CO slope between randomization and 6 months thereafter
Secondary endpoints 1
- Changes in (1) Peak VO2 (2) Mitral effective regurgitant orifice area (EROA) (3) Natriuretic peptide levels (NTproBNP) (4) Left atrial volume (Left Atrial Volume Index, LAVI) (5) Left atrial function (Peak Atrial Longitudinal Strain, PALS) (6) VE/VCO2 slope (7) Patient reported outcomes (Kansas City Cardiomyopathy Questionnaire, KCCQ-12)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 3
Entresto 49 mg/51 mg film-coated tablets
PRD3417302 · Product
- Active substance
- Valsartan
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 194 mg milligram(s)
- Max total dose
- 194 mg milligram(s)
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- C09DX04 — -
- Marketing authorisation
- EU/1/15/1058/002
- MA holder
- NOVARTIS EUROPHARM LIMITED
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Entresto 24 mg/26 mg film-coated tablets
PRD3417298 · Product
- Active substance
- Valsartan
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 194 mg milligram(s)
- Max total dose
- 194 mg milligram(s)
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- C09DX04 — -
- Marketing authorisation
- EU/1/15/1058/001
- MA holder
- NOVARTIS EUROPHARM LIMITED
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Entresto 97 mg/103 mg film-coated tablets
PRD3417299 · Product
- Active substance
- Valsartan
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 194 mg milligram(s)
- Max total dose
- 194 mg milligram(s)
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- C09DX04 — -
- Marketing authorisation
- EU/1/15/1058/005
- MA holder
- NOVARTIS EUROPHARM LIMITED
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Ziekenhuis Oost Limburg
- Sponsor organisation
- Ziekenhuis Oost Limburg
- Address
- Synaps Park 1
- City
- Genk
- Postcode
- 3600
- Country
- Belgium
Scientific contact point
- Organisation
- Ziekenhuis Oost Limburg
- Contact name
- Clinical Trial Unit
Public contact point
- Organisation
- Ziekenhuis Oost Limburg
- Contact name
- Clinical Trial Unit
Locations
1 EU/EEA country · 2 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Belgium | Ended | 110 | 2 |
| Rest of world | — | 0 | — |
Investigational sites
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 |
|---|---|---|---|---|---|
| Belgium | 2024-02-29 | 2026-03-10 | 2024-02-29 | 2025-09-24 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-07-17 | Belgium | Acceptable 2023-10-11
|
2023-10-11 |