Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes.
Condition: Heart Failure
MeSH terms: Heart Failure
Intervention: LCZ696 (sacubitril/valsartan)
Intervention description: LCZ696 (sacubitril/valsartan) was supplied as unscored, ovaloid, film-coated oral tablets in the strengths of 24/26 mg, 49/51 mg, 97/103 mg to be taken twice daily (bid)
Intervention MeSH terms: Valsartan; Sacubitril and valsartan sodium hydrate drug combination
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 794.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Heart failure; Reduced left ventricular ejection fraction; HFrEF; NT-proBNP; Cardiac remodeling; sacubitril/valsartan; KCCQ; biomarkers

Summary:

      This study was to determine early and more chronic changes in concentrations of biomarkers
      related to mechanisms of action (MOA) and effects of sacubitril/valsartan therapy over a
      period of 12 months, and correlated these biomarker changes with cardiac remodeling
      parameters, patient-reported outcomes and cardiovascular outcomes.
    

Eligibility criteria:

        Inclusion Criteria:

        Based on the USPI for sacubitril/valsartan, subjects eligible for inclusion in this study
        must fulfill all of the following criteria at screening and baseline:

          1. Written informed consent must be obtained before any assessment is performed.

          2. Men and women ≥ 18 years of age.

          3. LVEF ≤ 40% subjects who are candidates for on-label sacubitril/valsartan treatment per
             standard of care.

          4. New York Heart Association (NYHA) Functional class II-IV.

          5. LVEF ≤40% via any local measurement within the past 6 months using echocardiography,
             multi gated acquisition scan (MUGA), CT scanning, MRI or ventricular angiography
             provided no subsequent study documenting an EF of >40%. If the EF measurement is
             expressed as a value range, the average of the range endpoint values should be used as
             the EF.

          6. If a subject is on a loop diuretic, they must be on a stable dose for 2 weeks prior to
             baseline.

        Key Exclusion Criteria:

        Subjects fulfilling any of the following criteria, at screening and prior to dispensing of
        study drug, are not eligible for inclusion in this study. No additional exclusions may be
        applied by the investigator, in order to ensure that the study population will be
        representative of all eligible subjects/subjects.

          1. pregnant or nursing women

          2. women of child bearing potential not using highly effective method of contraception
             during dosing and for 7 days after stopping study medication

          3. History of hypersensitivity to any of the study drugs, including history of
             hypersensitivity to drugs of similar chemical classes, or allergy to angiotensin
             converting enzyme inhibitor (ACEIs), Angiotensin II Receptor Blockers (ARBs), or
             Neutral endopeptidase (NEP) inhibitors as well as known or suspected contraindications
             to the study drugs.

          4. History of angioedema drug related or otherwise.

          5. Requirement of treatment with either ACE inhibitor and/or ARB.

          6. Subjects with a heart transplant or ventricular assistance device (VAD) or intent to
             transplant (on transplant list) or implant a VAD.

          7. Subjects with a cardio resynchronization therapy devices (CRT/CRT-D) implanted within
             6 months of screening visit.

          8. Subjects who are currently taking inotropic agents.

          9. Current or prior treatment with sacubitril/valsartan.

         10. Subjects taking medications prohibited by the protocol.

         11. Subjects with diabetes mellitus who are taking aliskiren.

         12. Use of other investigational drugs within 5 half-lives of enrollment, or within 30
             days until the expected pharmacodynamic effect has returned to baseline, whichever is
             longer.

         13. Concomitant use of nesiritide.

         14. Bile acid sequestering agents such as cholestyramine or colestipol are prohibited to
             avoid interference with study drug absorption.

         15. Any hospital admission/discharge related to heart failure within 2 weeks prior to
             baseline.

         16. The use of outpatient or inpatient i.v. diuretic therapy within 2 weeks prior to
             baseline.

         17. Enrollment in another clinical trial within 30 days of screening.

         18. Potassium > 5.2 mEq/L at screening.

         19. History of malignancy of any organ system (other than localized basal cell carcinoma
             of the skin), treated or untreated, within one year.