Sacubitril-valsartan Versus Usual Anti-hypertensives in LVAD

Sacubitril-valsartan (Entresto) Versus Standard Anti-hypertensive Therapy in LVAD Patients - A Feasibility Pilot Study

This pilot, feasibility study evaluates the efficacy of sacubitril-valsartan (Entresto) versus usual anti-hypertensive medications in patients with left ventricular assist devices (LVAD). It also measures diurnal blood pressure variations in the context of continuous flow physiology.

Study Overview

• Status: Withdrawn
• Conditions: Hypertension; Congestive Heart Failure
• Intervention / Treatment: Drug: Entresto; Drug: Valsartan

Detailed Description

Left ventricular assist devices (LVAD) have become a life-saving therapy for patients with ACC/AHA stage D congestive heart failure (CHF). Despite longevity and improved quality of life, LVAD-supported patients are plagued with adverse events, the most debilitating of all is stroke. Ischemic and hemorrhagic strokes have been associated with hypertension (mean arterial pressure, or MAP > 90 mmHg) in addition to out-of-range INR and aspirin doses. Strict blood pressure control has been shown in a recent randomized trial to confer a significant decline in stroke rates of patients implanted with the Heartware LVAD. Patients with poorly controlled hypertension are also at risk for inadequate left-ventricular unloading and worsening CHF due to the exquisite sensitivity to afterload of the continuous flow LVAD.

There are no guidelines for the use of anti-hypertensives in LVAD patients. Most are started on standard CHF therapies, though this practice varies greatly across LVAD centers. The angiotensin receptor blocker-neprilysin inhibitor sacubitril-valsartan (Entresto) is a potent anti-hypertensive mediation that was recently approved by the Food and Drug Administration for the treatment of patients with heart failure and low ejection fraction. We aim to randomly assign patients to receive Entresto or usual anti-hypertensive therapy for blood pressure control, then crossover to the other arm after 30 days. Daily blood pressure measurements will be performed and correlated with LVAD pump flows and waveform analysis.

• Study Type: Interventional
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• More than 30 days after LVAD implant
• Ambulatory
• MAP > 85 mmHg requiring initiation of anti-hypertensive medications

Exclusion Criteria:

• Allergy to ACEI or ARB
• eGFR < 30 mL/min/1.73m2
• K > 5.4 mmol/L
• MAP < 60
• Inability to check blood pressure at home
• Lack of prescription coverage
• Frequent hospitalizations (monthly)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Entresto; First-line anti-hypertensive: sacubitril-valsartan, starting at 24-26 mg twice daily, increasing to maximum dose of 97-103 mg twice daily	Drug: Entresto; First line therapy in Entresto arm; Drug: Valsartan; First line therapy in "usual meds" arm
Active Comparator: Usual meds; First-line anti-hypertensive: valsartan, starting at 40 mg twice daily, increasing to a maximum dose of 160 mg twice daily	Drug: Entresto; First line therapy in Entresto arm; Drug: Valsartan; First line therapy in "usual meds" arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time spent with MAP < 85 mmHg	Daily mean arterial pressure (MAP) < 85 mmHg	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of drugs	Number of anti-hypertensive drugs needed to achieve MAP < 85 mmHg	2 months
Pump flow	Correlation of pump flow with daily MAP	2 months

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Collaborators: Medtronic
• Investigators: Principal Investigator: Van-Khue Ton, MD PhD, University of Maryland

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2017
• Primary Completion (Anticipated): November 1, 2018
• Study Completion (Anticipated): November 1, 2019

Study Registration Dates

• First Submitted: September 8, 2017
• First Submitted That Met QC Criteria: September 11, 2017
• First Posted (Actual): September 12, 2017

Study Record Updates

• Last Update Posted (Estimate): May 5, 2023
• Last Update Submitted That Met QC Criteria: May 4, 2023
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Valsartan; Sacubitril and valsartan sodium hydrate drug combination
• Other Study ID Numbers: HP-00076889

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No