Sacubitril-valsartan and Heart Failure Patients : the ENTRESTO-SAS Study
- Conditions
- Chronic Heart FailureSleep Apnea Syndrome
- Interventions
- Registration Number
- NCT02916160
- Lead Sponsor
- University Hospital, Montpellier
- Brief Summary
Chronic Heart Failure (CHF) is a frequent pathology burdened with mortality and significant morbidity. Sleep apnea syndrome (SAS) is frequently associated with CHF in 20% to 75% of cases. Treatment of SAS is however inconsistently associated with a decline in the morbidity and mortality. To date, the CHF medical treatments have been reported to be inconsistently efficient in the treatment of SAS.
SACUBITRIL-VALSARTAN (ENTRESTO®) is a new treatment of CHF recently indicated class I, level B in the recent European Society of Cardiology (ESC) guidelines 2016 on CHF. PARADIGM-HF trial demonstrated that morbidity and mortality can be improved with SACUBITRIL-VALSARTAN. In comparison to enalapril, it reduced the occurrence of cardiovascular death or hospitalisation for CHF by 20% with a 16% reduction in all-cause mortality.
The purpose of the research is the evaluation of SACUBITRIL-VALSARTAN combination in CHF patients presenting sleep apnea syndrome. A three months real life observational trial is performed. A measure of the Apnea Hypopnea Index is realised before and after 3 months of SACUBITRIL-VALSARTAN treatment. A concomitant evaluation of cardiological and quality of life parameters is realized.
- Detailed Description
The Chronic Heart Failure (CHF) is a frequent pathology burdened with mortality and significant morbidity. Chronic HF provides almost 2% of health expenditure in developed countries, it is the largest expenditure item in the USA (34.8 billion dollars). In most developed countries, including France, mortality 1 year after diagnosis of chronic HF is 40%, it is 50% at 2 years, and over 70% at 4.5 years.
Sleep apnea syndrome (SAS) is frequently associated with HF in 20% to 75% of cases. The presence of an apnea syndrome is associated with a greater morbidity and mortality. Treatment of SAS is however inconsistently associated with a decline in the morbidity and mortality. To date, the CHF medical treatments have been reported to be inconsistently efficient in the treatment of SAS : 6 studies corresponding to a total of 67 patients and 5 types of molecules reported an incomplete effect on the central component of the Apnea Hypopnea Index (AHI) for these patients.
SACUBITRIL - VALSARTAN (ENTRESTO®) is a new treatment of HF recently indicated class I, level B in the recent ESC guidelines 2016 on HF. It combines inhibitory prodrug neprilysin and valsartan. After initial failures with neprilysin inhibition alone or dual neprilysin-angiotensin converting enzyme (ACE) inhibition, the PARADIGM-HF trial demonstrated that morbidity and mortality can be improved with the SACUBITRIL - VALSARTAN combination (formerly LCZ696). In comparison to the ACE inhibitor enalapril, sacubitril/valsartan reduced the occurrence of the primary end point (cardiovascular death or hospitalisation for HF) by 20% with a 16% reduction in all-cause mortality. These findings suggest that sacubitril/valsartan should replace an ACE inhibitor or angiotensin receptor blocker as the foundation of treatment of symptomatic patients (NYHA II-IV) with HF and a reduced ejection fraction.
The purpose of the research is the evaluation of SACUBITRIL-VALSARTAN in CHF patients presenting sleep apnea syndrome. We speculate that synchronously of a beneficial effect on heart failure, the SACUBITRIL-VALSARTAN combination could improve an associated SAS and in particular the central component of the AHI index.
After an exhaustive initial pre-therapeutic evaluation, the SACUBITRIL-VALSARTAN combination treatment is initiated for 3 months.
The pre-therapeutic evaluation includes cardiological and biological exams, quality of life questionaries and nocturnal ventilatory polygraphy.
Considering the results of the polygraphy, three groups of patients are identified:
* group 1 patients, characterized by a central AHI ≥5 / h and an obstructive AHI \<15 / h,
* group 2 patients, characterized by an obstructive AHI ≥15 / h whatever is the central component. In this group of patient, a ventilator treatment with constant positive airway pressure or auto-servoventilation is started.
* group 3 patients, characterized by a central AHI \< 5 / h and an obstructive AHI \<15 / h.
After three months of treatment, the final evaluation includes cardiological and biological exams, quality of life questionaries for all the patient included in the trial. A nocturnal polygraphy is performed only in group 1 and 2 patients. For group 2 patients treated with a device, the observance to the device, the residual AHI device and the pressure device is measured.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 124
- Age is greater than or equal to 18 years
- Patient with chronic heart failure (LVEF ≤ 45%).
- Written informed consent
- Renal insufficiency (GF<30 milliliters/min)
- Pregnancy
- Allergy to one compound
- Personal history of angiooedema
- Hemodynamical instability
- Severe hepatopathy
- Current and not treated hyperkaliemia
- Prognosis < 6months
- Current CPAP or ASV treatment for Sleep Apnea Syndrome
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description SACUBITRIL - VALSARTAN SACUBITRIL - VALSARTAN (formerly LCZ696, ENTRESTO®) SACUBITRIL - VALSARTAN (formerly LCZ696, ENTRESTO®) is a new treatment of HF recently indicated class I, level B in the recent ESC guidelines 2016 on HF. It combines inhibitory prodrug neprilysin and valsartan.
- Primary Outcome Measures
Name Time Method Changes in Apnea-Hypopnea Index as compared to baseline 0 month to 3 months Changes in AHI as compared to baseline Measure of the apnea hypopnea index by a polygraphy performed before and after 3 months of treatment. The 2012 American Academy of Sleep Medicine recommendations are utilized in order to characterized apnea and hypopnea events, the central or obstructive or mixed phenotype
- Secondary Outcome Measures
Name Time Method Subject Global Assessment 0 month to 3 months NYHA Functional Class 0 month to 3 months Heart Rhythm 0 month to 3 months physiological parameter
Systolic and diastolic Blood Pressure 0 month to 3 months physiological parameter
Renal function as compared to baseline (Estimated GFR (eGFR) will be calculated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula 0 month to 3 months CKD-EPI formula
BNP (B-type Natriuretic Peptide) rates 0 month to 3 months Biological parameter
Subject medications 0 month to 3 months Quality of life as measured by Minnesota Living with Heart Failure Questionary 0 month to 3 months Questionaries
Quality of life as measured by EQ-5D-3L Questionary 0 month to 3 months Questionaries
Epworth Sleepiness Scale 0 month to 3 months Questionary
Pichot Fatigue Scale 0 month to 3 months Questionary
Type of device used in group 2 patients 0 month to 3 months CPAP or ASV device CPAP/ASV : continuous positive airway pressure / adaptive servo ventilation
CPAP/ASV compliance in group 2 patients 0 month to 3 months CPAP/ASV compliance. Unit : number of hour per day using CPAP/ASV device
Historical of CPAP/ASV compliance in group 2 patients 0 month to 3 months CPAP/ASV compliance. Unit : number of day with ≥3 hours in the past 6 months
Settings of CPAP/ASV device used in group 2 patients 0 month to 3 months Settings of device
Type of mask used in group 2 patients 0 month to 3 months Type of mask
Historical use of mask in group 2 patients 0 month to 3 months Historical use of mask
Changes in AHI compared to Baseline in group 2 patients 0 month to 3 months Changes in AHI compared to Baseline
Trial Locations
- Locations (6)
CHU Nimes
🇫🇷Nimes, France
CHU Bordeaux
🇫🇷Bordeaux, Pessac, France
Centre Hospitalier Universitaire de Montpellier
🇫🇷Montpellier, France
CHU Béziers
🇫🇷Béziers, France
Pôle médical spécialisé MSP
🇫🇷Béziers, France
CHU Toulouse
🇫🇷Toulouse, France