Heart FailureNCT04434170
Effects of Sacubitril/Valsartan on Exercise Capacity, Natriuretic Peptides and Ventricular Remodeling in Heart Failure
An observational study of Heart Failure, run by Centro Cardiologico Monzino at 1 site in Italy.
Trial summary
Background: Sacubitril/valsartan, a novel therapy in the treatment of heart failure with reduced ejection fraction (HFrEF), has recently proved efficacy in improving exercise tolerance and cardiac performance. Cardiopulmonary exercise test (CPET) provides functional prognostic parameters for patient with HFrEF (i.e. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Heart Failure
- What is being tested?
- Sacubitril-Valsartan
- How many people
- 112 participants
- Where
- 1 siteItaly
- Study dates
- 15 Oct 2018to 15 Dec 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: HFrEF outpatients eligible for sacubitril/valsartan according to guidelines and perform serial CPET, laboratory and echocardiographic assessments before and during the gradual titration of the treatment
Who may be able to join
- New York Heart Association Class (NYHA) II-III
- stable clinical conditions
- reduced ejection fraction (< 35%)
- capability to perform a cardiopulmonary exercise test (CPET)
Who cannot join
- moderate-severe chronic obstructive pulmonary disease
- chronic oxygen therapy
- contraindication to CPET
- planned procedures (i.e. cardiac surgery, revascularization procedures, CRT implantation) that could per se impact on CPET, echocardiography and laboratory values
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Valutazione Della capacità d'Esercizio, Della funzionalità Respiratoria e Del Rimodellamento Ventricolare Sinistro in Pazienti Affetti da Scompenso Cardiaco a Frazione d'Eiezione Ridotta Trattati Con Sacubitril/Valsartan
Background: Sacubitril/valsartan, a novel therapy in the treatment of heart failure with reduced ejection fraction (HFrEF), has recently proved efficacy in improving exercise tolerance and cardiac performance. Cardiopulmonary exercise test (CPET) provides functional prognostic parameters for patient with HFrEF (i.e. peakVO2 and ventilation/CO2 production [VE/VCO2] slope) and it is a well-recognized, valuable, accurate tool for risk stratification.
Aim of the study and methods: The aim of the study is to prospectively enroll a cohort of 100 HFrEF outpatients eligible for sacubitril/valsartan and perform serial CPET, laboratory and echocardiographic assessments before and during the gradual titration of the treatment, in order to evaluate its effects on cardiopulmonary function and left ventricular remodeling. The procedures will be repeated along the follow-up at 1, 2 and 3 months after the enrollment (titration period) and at 6 months after the reach of the maximum tolerated dose.
Read the detailed description
Given the recent introduction of the drug into the clinical routine, the evaluation of the experience "on the field" is important to refine the clinical management of patients treated with sacubitril / valsartan. Furthermore, at the moment sacubitril / valsartan has proven effective in some small preliminary studies in improving the ejection fraction and some echocardiographic parameters of ventricular remodeling on top of the concomitant optimal medical therapy, although further data are needed in this regard.
In particular, the potential benefits on exercise capacity, respiratory function parameters and left ventricular remodeling in heart failure patients treated with sacubitril / valsartan has not been studied extensively at the moment. In this regard, the cardiopulmonary exercise test (CPET) allows to obtain prognostic functional parameters in patients with chronic heart failure such as peak V02 (peak V02) and the ventilation / production of C02 slope (VE / VC02 slope). CPET is a valid, recognized and accurate tool for risk stratification in heart failure patients.
Furthermore, few data are available on lung diffusion (DLCO) and on specific markers of the alveolar-capillary membrane, such as type B surfactant proteins (SPB) in patients treated with sacubtril / valsartan. Our team has already shown how these biomarkers and DLCO are influenced by drug treatments such as Levosimendan and Ace inhibitors.
The aim of the study is to evaluate the exercise capacity, spirometry, echocardiographic parameters of left ventricular sistolic and diastolic function, Nt-proBNP dosage and quality of life and the related dose-effect correlation in a multicenter cohort of 100 patients with stable heart failure (class functional NYHA II e lII) and reduced left ventricular ejection fraction in patients eligible for sacubitril / valsartan treatment.
A subgroup of patients will be also analyzed for data relating to the effect of sacubitril / valsartan on DLCO and blood levels of Surfactant Bindig protein (SPB).
Sacubitril / Valsartan will be prescribed according to guidelines, initially at the lowest dosage of 24/26 mg b.i.d. to verify its tolerability with the prospect of gradually increasing the dosage during subsequent follow-up visits. The re-evaluation of the treatment and the titration of the sacubitril / valsartan dose will take place every 4 weeks until the maximum tolerated dose is reached. The dose under study will be the maximum tolerated by the patient (however not higher than 97 mg / 103mg bd).
Cardiological examination with ECG, spirometry, CPET, the Kansas City Cardiomyopathy Questionnaire, blood count, creatinine, nitrogen, sodium, potassium, chlorine and NTproBNP will be performed at each visit (from Baseline to 6 months). The colordoppler echocardiogram will instead be performed only at the baseline and after 6 months.
A subset of patients will also be subjected to analysis of the blood levels of SPB and DLCO at baseline and 6 months after reaching the maximum tolerated dose.
- Conditions
- Heart Failure
- Being tested
- Sacubitril-Valsartan
- Keywords
- sacubitril/valsartan, exercise, cardiopulmonary exercise test, left ventricular remodeling
- Medical subject headings
- Heart Failure, Motor Activity, Ventricular Remodeling
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sacubitril-ValsartanDrug
outpatients who start treatment with sacubitril/valsartan according to guidelines will andergo cardiopulmonary exercise testing evaluation
| Study group | Role | What they receive |
|---|---|---|
| Heart failure | outpatients with heart failure with reduced ejection fraction in treatment with sacubitril/valsartan according to guidelines Receives: Drug: Sacubitril-Valsartan |
What is being measured
The primary outcome is the main question the study is designed to answer.
VO2 evaluation after treatment
changes in peak VO2 at cardiopulmonary exercise test
Measured: 1 month after start of treatment with sacubitril/valsartan
VO2 evaluation after treatment
changes in peak VO2 at cardiopulmonary exercise test
Measured: 2 months after start of treatment with sacubitril/valsartan
VO2 evaluation after treatment
changes in peak VO2 at cardiopulmonary exercise test
Measured: 3 months after start of treatment with sacubitril/valsartan
VO2 evaluation after treatment
changes in peak VO2 at cardiopulmonary exercise test
Measured: 9 months after start of treatment with sacubitril/valsartan
Secondary outcomes (14)
lung function evaluation after treatment
changes in FVC, FEV1, PEF and FEV1%, by spirometry
Measured: 1 month after start of treatment with sacubitril/valsartan
lung function evaluation after treatment
changes in FVC, FEV1, PEF and FEV1%, by spirometry
Measured: 2 months after start of treatment with sacubitril/valsartan
lung function evaluation after treatment
changes in FVC, FEV1, PEF and FEV1%, by spirometry
Measured: 3 months after start of treatment with sacubitril/valsartan
lung function evaluation after treatment
changes in FVC, FEV1, PEF and FEV1%, by spirometry
Measured: 9 months after start of treatment with sacubitril/valsartan
DLCO
DLCO evaluation
Measured: 1 month after start of treatment with sacubitril/valsartan
DLCO
DLCO evaluation
Measured: 9 months after start of treatment with sacubitril/valsartan
Surfactant B-type protein after treatment
SPB quantification
Measured: 1 month after start of treatment with sacubitril/valsartan
Surfactant B-type protein after treatment
SPB quantification
Measured: 9 months after start of treatment with sacubitril/valsartan
left ventricular remodeling
ejection fraction
Measured: 1 month after start of treatment with sacubitril/valsartan
left ventricular remodeling
ejection fraction
Measured: 2 months after start of treatment with sacubitril/valsartan
left ventricular remodeling
ejection fraction
Measured: 9 months after start of treatment with sacubitril/valsartan
left ventricular remodeling
End-diastolic and end-systolic left ventricular volumes
Measured: 1 month after start of treatment with sacubitril/valsartan
left ventricular remodeling
End-diastolic and end-systolic left ventricular volumes
Measured: 2 months after start of treatment with sacubitril/valsartan
left ventricular remodeling
End-diastolic and end-systolic left ventricular volumes
Measured: 9 months after start of treatment with sacubitril/valsartan
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2020
- Study start15 Oct 2018
- Primary completion30 Nov 2020
- Study completion15 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 112 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centro Cardiologico Monzino
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Piergiuseppe Agostoni, Centro Cardiologico Monzino
- Investigators
- Piergiuseppe Agostoni, MD, Principal investigator, Centro Cardiologico Monzino
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04434170
- Sponsor's protocol ID
- Entresto CPET
- Status last verified
- Feb 2024
- First submitted
- 4 Jun 2020
- Last updated
- 7 Feb 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Valutazione Della capacità d'Esercizio, Della funzionalità Respiratoria e Del Rimodellamento Ventricolare Sinistro in Pazienti Affetti da Scompenso Cardiaco a Frazione d'Eiezione Ridotta Trattati Con Sacubitril/Valsartan
- ClinicalTrials.gov ID
- NCT04434170
- Acronym / sponsor ID
- Entresto CPET
- Conditions
- Heart Failure
- Keywords
- sacubitril/valsartan, exercise, cardiopulmonary exercise test, left ventricular remodeling
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 112 participants (actual)
- Lead sponsor
- Centro Cardiologico MonzinoUniversity, hospital or other
- Study start
- 15 Oct 2018 (actual)
- Primary completion
- 30 Nov 2020 (actual)
- Study completion
- 15 Dec 2021 (actual)
- First posted
- 16 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background: Sacubitril/valsartan, a novel therapy in the treatment of heart failure with reduced ejection fraction (HFrEF), has recently proved efficacy in improving exercise tolerance and cardiac performance. Cardiopulmonary exercise test (CPET) provides functional prognostic parameters for patient with HFrEF (i.e. peakVO2 and ventilation/CO2 production [VE/VCO2] slope) and it is a well-recognized, valuable, accurate tool for risk stratification.
Aim of the study and methods: The aim of the study is to prospectively enroll a cohort of 100 HFrEF outpatients eligible for sacubitril/valsartan and perform serial CPET, laboratory and echocardiographic assessments before and during the gradual titration of the treatment, in order to evaluate its effects on cardiopulmonary function and left ventricular remodeling. The procedures will be repeated along the follow-up at 1, 2 and 3 months after the enrollment (titration period) and at 6 months after the reach of the maximum tolerated dose.
Detailed description
Given the recent introduction of the drug into the clinical routine, the evaluation of the experience "on the field" is important to refine the clinical management of patients treated with sacubitril / valsartan. Furthermore, at the moment sacubitril / valsartan has proven effective in some small preliminary studies in improving the ejection fraction and some echocardiographic parameters of ventricular remodeling on top of the concomitant optimal medical therapy, although further data are needed in this regard.
In particular, the potential benefits on exercise capacity, respiratory function parameters and left ventricular remodeling in heart failure patients treated with sacubitril / valsartan has not been studied extensively at the moment. In this regard, the cardiopulmonary exercise test (CPET) allows to obtain prognostic functional parameters in patients with chronic heart failure such as peak V02 (peak V02) and the ventilation / production of C02 slope (VE / VC02 slope). CPET is a valid, recognized and accurate tool for risk stratification in heart failure patients.
Furthermore, few data are available on lung diffusion (DLCO) and on specific markers of the alveolar-capillary membrane, such as type B surfactant proteins (SPB) in patients treated with sacubtril / valsartan. Our team has already shown how these biomarkers and DLCO are influenced by drug treatments such as Levosimendan and Ace inhibitors.
The aim of the study is to evaluate the exercise capacity, spirometry, echocardiographic parameters of left ventricular sistolic and diastolic function, Nt-proBNP dosage and quality of life and the related dose-effect correlation in a multicenter cohort of 100 patients with stable heart failure (class functional NYHA II e lII) and reduced left ventricular ejection fraction in patients eligible for sacubitril / valsartan treatment.
A subgroup of patients will be also analyzed for data relating to the effect of sacubitril / valsartan on DLCO and blood levels of Surfactant Bindig protein (SPB).
Sacubitril / Valsartan will be prescribed according to guidelines, initially at the lowest dosage of 24/26 mg b.i.d. to verify its tolerability with the prospect of gradually increasing the dosage during subsequent follow-up visits. The re-evaluation of the treatment and the titration of the sacubitril / valsartan dose will take place every 4 weeks until the maximum tolerated dose is reached. The dose under study will be the maximum tolerated by the patient (however not higher than 97 mg / 103mg bd).
Cardiological examination with ECG, spirometry, CPET, the Kansas City Cardiomyopathy Questionnaire, blood count, creatinine, nitrogen, sodium, potassium, chlorine and NTproBNP will be performed at each visit (from Baseline to 6 months). The colordoppler echocardiogram will instead be performed only at the baseline and after 6 months.
A subset of patients will also be subjected to analysis of the blood levels of SPB and DLCO at baseline and 6 months after reaching the maximum tolerated dose.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Heart failure | – | Drug: Sacubitril-Valsartanoutpatients with heart failure with reduced ejection fraction in treatment with sacubitril/valsartan according to guidelines |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- HFrEF outpatients eligible for sacubitril/valsartan according to guidelines and perform serial CPET, laboratory and echocardiographic assessments before and during the gradual titration of the treatment
Key inclusion criteria (4 listed)
- New York Heart Association Class (NYHA) II-III
- stable clinical conditions
- reduced ejection fraction (< 35%)
- capability to perform a cardiopulmonary exercise test (CPET)
Key exclusion criteria (4 listed)
- moderate-severe chronic obstructive pulmonary disease
- chronic oxygen therapy
- contraindication to CPET
- planned procedures (i.e. cardiac surgery, revascularization procedures, CRT implantation) that could per se impact on CPET, echocardiography and laboratory values
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sacubitril-Valsartanoutpatients who start treatment with sacubitril/valsartan according to guidelines will andergo cardiopulmonary exercise testing evaluation | Drug | Heart failure |
Primary outcome
VO2 evaluation after treatment
Time frame: 1 month after start of treatment with sacubitril/valsartan
changes in peak VO2 at cardiopulmonary exercise test
VO2 evaluation after treatment
Time frame: 2 months after start of treatment with sacubitril/valsartan
changes in peak VO2 at cardiopulmonary exercise test
VO2 evaluation after treatment
Time frame: 3 months after start of treatment with sacubitril/valsartan
changes in peak VO2 at cardiopulmonary exercise test
VO2 evaluation after treatment
Time frame: 9 months after start of treatment with sacubitril/valsartan
changes in peak VO2 at cardiopulmonary exercise test
14 secondary outcomes
lung function evaluation after treatment
Time frame: 1 month after start of treatment with sacubitril/valsartan
lung function evaluation after treatment
Time frame: 2 months after start of treatment with sacubitril/valsartan
lung function evaluation after treatment
Time frame: 3 months after start of treatment with sacubitril/valsartan
lung function evaluation after treatment
Time frame: 9 months after start of treatment with sacubitril/valsartan
DLCO
Time frame: 1 month after start of treatment with sacubitril/valsartan
DLCO
Time frame: 9 months after start of treatment with sacubitril/valsartan
Surfactant B-type protein after treatment
Time frame: 1 month after start of treatment with sacubitril/valsartan
Surfactant B-type protein after treatment
Time frame: 9 months after start of treatment with sacubitril/valsartan
left ventricular remodeling
Time frame: 1 month after start of treatment with sacubitril/valsartan
left ventricular remodeling
Time frame: 2 months after start of treatment with sacubitril/valsartan
left ventricular remodeling
Time frame: 9 months after start of treatment with sacubitril/valsartan
left ventricular remodeling
Time frame: 1 month after start of treatment with sacubitril/valsartan
left ventricular remodeling
Time frame: 2 months after start of treatment with sacubitril/valsartan
left ventricular remodeling
Time frame: 9 months after start of treatment with sacubitril/valsartan
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2024.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Piergiuseppe Agostoni, MD principal investigator
Centro Cardiologico Monzino
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Heart Failure, run by Centro Cardiologico Monzino at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
VO2 evaluation after treatment (time frame: 1 month after start of treatment with sacubitril/valsartan). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2024.