NCT02788656

Pulmonary Artery Pressure Reduction With ENTresto (Sacubitril/Valsartan)

PARENT Trial Pilot Pulmonary Artery Pressure Reduction With ENTresto (Sacubitril/Valsartan)

• Status: Terminated
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 4 (actual)
• Sponsor: Brigham and Women's Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This pilot study will assess the impact of sacubitril/valsartan (trade name Entresto) on the elevated pulmonary artery pressures in patients with heart failure with reduced ejection fraction, measured using a previously implanted hemodynamic monitoring device (CardioMEMS).

Detailed description

Angiotensin-converting enzyme inhibitors (ACEi) have been a cornerstone treatment for patients with heart failure and reduced ejection fraction (HFrEF) for over 25 years. They are included in every major set of guidelines for HFrEF management. Angiotensin receptor blockers (ARB's, such as valsartan) have similarly been shown to decrease the mortality rate of patients with HFrEF for patients who are unable to tolerate ACEi therapy. The newest neurohormonal therapy approved for heart failure (August 2015) is sacubitril/valsartan (trade name Entresto). This medication is the first of a new family of agents (ARNI = angiotensin receptor antagonist with neprilysin inhibitor), combining the approved angiotensin receptor blocker valsartan with sacubitril, an inhibitor of neprilysin, which is a neutral endopeptidase that degrades endogenous vasoactive peptides. Treatment with sacubitril increases circulating levels of natriuretic peptides, which have been shown to facilitate natriuresis and vasodilation. Although the precise mechanisms responsible for benefit in heart failure remain unclear, sacubitril/valsartan may reduce the fluid retention and vasoconstriction that contribute to heart failure symptoms, and may also decrease apoptosis and remodeling that lead to disease progression. There is limited data about the incremental acute and long-term hemodynamic effects of composite neprilysin/angiotensin-receptor inhibitors over enalapril, and these data may provide important mechanistic insights. Progress in HF management outside the hospital has included validation of a strategy of ongoing monitoring of pulmonary artery pressures every day from home via a monitor implanted in a distal pulmonary artery, the CardioMEMS device. The information is transmitted to a website where it is reviewed by the HF team, who can intervene to adjust diuretics and other medications by phone to avert decompensation and re-hospitalization. The device received FDA approval in mid 2014, and is now being implanted in many cardiac catheterization laboratories, including at Brigham and Women's Hospital. The pressure information is reviewed regularly by the HF management team who are in regular contact with the patient to aid in management decisions. In summary, this pilot study will assess the impact of sacubitril/valsartan, an approved drug for heart failure with reduced ejection fraction (HFrEF) on the elevated pulmonary artery pressures measured using an implanted monitoring device that is also approved for such patients. Both the medication and the device will be used according to approved indications.

Conditions

• Congestive Heart Failure

Interventions

Type	Name	Description
DEVICE	Implantable Hemodynamic Monitor	The CardioMEMS device is an implantable pulmonary artery pressure monitor that is FDA-approved for use in patients with symptomatic heart failure and previous heart failure hospitalization. Patients eligible for this study are those with an already implanted CardioMEMS device.
DRUG	Angiotensin-Converting Enzyme Inhibitor	Conventional, guideline-directed therapy for heart failure and reduced ejection fraction
DRUG	Angiotensin II Type 1 Receptor Blocker	Conventional, guideline-directed therapy for heart failure and reduced ejection fraction in ACE-inhibitor intolerant patients
DRUG	sacubitril/valsartan	Angiotensin-neprilysin inhibitor that is now FDA-approved and guideline-directed therapy for patients with symptomatic heart failure and reduced ejection fraction despite treatment with an ACE-inhibitor/Angiotensin-Receptor Blocker

Timeline

• Start date: 2016-09-01
• Primary completion: 2018-11-09
• Completion: 2018-11-09
• First posted: 2016-06-02
• Last updated: 2020-02-17
• Results posted: 2020-02-17

Locations

1 site across 1 country: United States