comParIson Of Sacubitril/valsartaN Versus Enalapril on Effect on ntpRo-bnp in Patients Stabilized From an Acute Heart Failure Episode
- CTRC Outpatient
- Clements University Hospital
- UT Southwestern-Other
Jennifer Thibodeau, M.D.
A Multicenter, Randomized, Double-blind, Double Dummy, Parallel Group, Active-controlled 8-week Study to Evaluate the Effect of Sacubitril/Valsartan (LCZ696) Versus Enalapril on Changes in NT-proBNP and Safety and Tolerability of In-hospital Initiation of LCZ696 Compared to Enalapril in HFrEF Patients Who Have Been Stabilized Following Hospitalization for Acute Decompensated Heart Failure (ADHF).
The purpose of this study is to assess the effect of in-hospital initiation of sacubitril/valsartan (LCZ696) vs. enalapril on time averaged proportional change in NT-proBNP in patients who have been stabilized following hospitalization for acute decompensated heart failure (ADHF) and reduced ejection fraction (left ventricular ejection fraction (LVEF) ≤ 40%).
Key Inclusion Criteria:
1. Possess the capacity to provide written informed consent which must be obtained before any assessment is performed.
2. Currently hospitalized for ADHF. Patients with a diagnosis of acute heart failure had to have symptoms and signs of fluid overload (i.e. jugular venous distention, edema or rales on auscultation or pulmonary congestion on chest x-ray) at time of hospitalization.
3. Eligible patients will be randomized no earlier than 24 hours and up to ten days after presentation while still hospitalized as long as meet the following definition of stable status:
- SBP ≥100mm Hg for the preceding 6 hours prior to randomization; no symptomatic hypotension
- No increase (intensification) in i.v. diuretic dose within last 6 hours prior to randomization
- No i.v. inotropic drugs for 24 hours prior to randomization
- No i.v. vasodilators including nitrates within last 6 hours prior to randomization
4. LVEF ≤40% within the past 6 months (including current hospitalization) using echocardiography, multi gated acquisition scan (MUGA), CT scanning, MRI or ventricular angiography, provided no subsequent study documented an EF of >40%.
5. Elevated NT-proBNP ≥ 1600pg/mL OR BNP ≥400 pg/mL during current hospitalization.
Key Exclusion Criteria:
1. Currently taking sacubitril/valsartan tablets or any use within the past 30 days.
2. Enrollment in any other clinical trial involving an investigational agent or investigational device.
3. History of hypersensitivity, known or suspected contraindications, or intolerance to any of the study drugs, including ACEIs, ARBs, or Sacubitril (NEP inhibitor).
4. Patients with a known history of angioedema related to previous ACE inhibitor or ARB therapy.
5. Requirement of treatment with both ACE inhibitor and ARB.
6. eGFR < 30 ml/min/1.73 m2 as measured by the simplified Modification of Diet in Renal Disease (MDRD) formula at screening.
7. Serum potassium > 5.2 mEq/L at screening.
8. Known hepatic impairment (as evidenced by total bilirubin > 3 mg/dL, or increased ammonia levels, if performed), or history of cirrhosis with evidence of portal hypertension such as varices
9. Acute coronary syndrome, stroke, transient ischemic attack; cardiac, carotid or other major CV surgery; percutaneous coronary intervention (PCI) or carotid angioplasty, within one month prior to Visit 1.
10. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
11. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they are using two birth control methods.