Entresto + Aprepitant for Heart Failure
Trial Summary
What is the purpose of this trial?
This is a double-blind, randomized, two x two crossover (aprepitant vs placebo) during both initiation of Entresto, LCZ696, (50 mg dose) and at steady-state of Entresto (200 mg bid dose or the highest tolerated dose).
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but it requires that you are on a stable dose of certain heart medications like ACE inhibitors, ARBs, and beta blockers for at least four weeks. If you are taking a dipeptidyl peptidase-4 inhibitor for type 2 diabetes, you will need to stop it one month before joining the trial.
What data supports the effectiveness of the drug Entresto (sacubitril/valsartan) for heart failure?
Research shows that Entresto, a combination of sacubitril and valsartan, is effective in reducing the risk of cardiovascular death and hospitalization in patients with chronic heart failure. It has been found to be superior to enalapril, another heart failure medication, in reducing these risks.12345
Is the combination of Entresto and Aprepitant safe for humans?
Entresto (sacubitril/valsartan) has been studied for heart failure and is generally safe, but it can cause side effects like low blood pressure, swelling, kidney problems, and high potassium levels. It should not be used during pregnancy, breastfeeding, or with certain other medications in people with diabetes. There is no specific safety data available for the combination with Aprepitant.12467
What makes the drug Entresto unique for treating heart failure?
Entresto is unique because it combines two actions: it blocks angiotensin II receptors and inhibits neprilysin, which helps reduce the risk of cardiovascular death and hospitalization in heart failure patients. This dual action makes it more effective than some traditional treatments like enalapril.13456
Research Team
Nancy J. Brown, MD
Principal Investigator
Yale University
Eligibility Criteria
This trial is for black and white men and women, aged 18 or older, with heart failure (NYHA Class I-III) and an ejection fraction (EF) ≤55%. Participants must have stable symptoms, no recent hospitalizations for heart failure, not be on LCZ696 currently, and if female and of childbearing potential, use reliable contraception. Excluded are those with allergies to study drugs or related chemicals, history of angioedema or certain cardiovascular events within the last six months.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Washout and Initial Dosing
Participants undergo a 48-hour washout period, followed by a single dose of 50 mg LCZ696 with either aprepitant or placebo, then a 96-hour washout and repeat dosing with the opposite study drug.
Up-titration
Participants undergo up-titration of LCZ696 over seven weeks, starting with 50 mg bid for two weeks, then 100 mg bid for three weeks, and finally 200 mg bid or the highest tolerated dose.
Steady-State Evaluation
On the 7th and 10th days of the 200 mg bid or highest tolerated dose, participants undergo two more study days three days apart, receiving either aprepitant or placebo.
Follow-up
Participants are monitored for safety and effectiveness after treatment
Treatment Details
Interventions
- Aprepitant
- LCZ 696
- Placebo
LCZ 696 is already approved in United States, European Union for the following indications:
- Heart failure with reduced ejection fraction (NYHA Class II-IV)
- Heart failure with reduced ejection fraction (NYHA Class II-IV)
Find a Clinic Near You
Who Is Running the Clinical Trial?
Yale University
Lead Sponsor