For those not tolerating the current dose of study drug, the dose will be down-titrated to the previous tolerated dose. For subjects not previously taking ACEI or ARB, previously taking ACEI or ARB at a low dose*, or subjects who have an eGFR 90 mmHg is required for up titration), changes in renal function (maximum serum creatinine of 2.0 mg/dL), and the absence of symptoms of hypotension.Randomized subjects will receive the first dose of study drug as follows: Study treatment will be titrated to the target dose of 200 mg LCZ696 (equivalent to Entresto™ 97/103 mg) as two 100 mg LCZ696 and 2 placebo tablets po BID or valsartan 160 mg (two 80 mg valsartan and 2 placebo tablets) po BID.* Subjects who tolerate the run-in period with LCZ696 will be randomized 1:1 to LCZ696 or valsartan. For subjects taking an ACEI, the ACEI will be withheld for ≥ 36 hours prior to first dose of LCZ696. Those who meet all entry criteria and are interested in study participation will be enrolled.Įnrolled subjects will complete baseline assessments and undergo a run-in period of 3-7 days with LCZ696 50 mg (equivalent to Entresto™ 24/26 mg) po BID (taken by mouth twice a day) prior to randomization. Willing subjects meeting entry criteria will be consented. The LV ejection fraction may have been obtained within the prior 12 months by 2-D echocardiogram, LV angiogram or radionuclide scintigraphy. Subjects will have an initial screening evaluation, including baseline laboratory tests as well as an assessment of left ventricular (LV) ejection fraction, at which time preliminary subject eligibility will be determined.
Approximately 400 subjects will be randomized into the study. Study drug will be administered in a double-dummy fashion, in which subjects take active (LCZ696 or valsartan) and placebo.
#Entresto free 30 day trial trial#
This study will be a randomized, double-blinded trial of advanced heart failure subjects with 1:1 randomization to either LCZ696 (sacubitril and valsartan) or valsartan. Accordingly, experience is needed on the use of, and outcomes with LCZ696 in patients unable to tolerate target doses of angiotensin-converting enzyme inhibitor (ACEI)/ angiotensin receptor blocker (ARB). Because the information on the effects of sacubitril/valsartan in patients with NYHA class IV heart failure is limited, the updated 2016 ACC/AHA/HFSA guidelines for the treatment of heart failure do not yet endorse the use of sacubitril/valsartan in patients with NYHA class IV heart failure.
However, limited experience with advanced heart failure patients was gained from patients enrolled in the trial.
The PARADIGM-HF trial showed that LCZ696, which consists of the neprilysin inhibitor sacubitril and the ARB valsartan, improved morbidity and mortality in patients with chronic HFrEF in comparison to enalapril. For the most advanced heart failure patients, the evidence base for medical treatment is limited with consensus guidelines recommending consideration for either cardiac transplant or ventricular assist device, or palliative care. Patients with advanced heart failure with reduced ejection fraction (HFrEF) have extremely high morbidity and mortality with 1 year outcomes of death and hospitalization of approximately 50%.