Sacubitril-valsartan and Heart Failure Patients : the ENTRESTO-SAS Study
Condition: Chronic Heart Failure; Sleep Apnea Syndrome
MeSH terms: Apnea; Sleep Apnea Syndromes; Heart Failure; Syndrome
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): SACUBITRIL - VALSARTAN (formerly LCZ696, ENTRESTO®)
Intervention type(s): Drug
Intervention description(s): 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.
Other intervention name(s): LCZ696, ENTRESTO®
Intervention MeSH terms: Valsartan; Sacubitril and valsartan sodium hydrate drug combination
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Chronic Heart failure; Sleep Apnea Syndrome; Continuous Positive Airways Pressure; SACUBITRIL - VALSARTAN