Sacubitril-valsartan and Heart Failure Patients : the ENTRESTO-SAS Study (ENTRESTO696)

University Hospital Center (CHU)

Status and phase: Completed; Phase 4

Conditions: Sleep Apnea Syndrome; Chronic Heart Failure

Treatments: Drug: SACUBITRIL - VALSARTAN (formerly LCZ696, ENTRESTO®)

Study type: Interventional

Funder types: Other

Identifiers

NCT02916160

UF 9703

Details and patient eligibility

About

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.

Full 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.

Enrollment: 124 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age is greater than or equal to 18 years
• Patient with chronic heart failure (LVEF ≤ 45%).
• Written informed consent

Exclusion criteria

• 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

Trial design

Primary purpose: Other

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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124 participants in 1 patient group

SACUBITRIL - VALSARTAN

Experimental group

Description:

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.

Treatment:

Drug: SACUBITRIL - VALSARTAN (formerly LCZ696, ENTRESTO®)