Sacubitril-valsartan Versus Usual Anti-hypertensives in LVAD

NCT ID: NCT03279861

Last Updated: 2023-05-06

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-30
• Study Completion Date: 2019-11-30

Brief Summary

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.

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.

Conditions

Congestive Heart Failure; Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Entresto

First-line anti-hypertensive: sacubitril-valsartan, starting at 24-26 mg twice daily, increasing to maximum dose of 97-103 mg twice daily

Group Type: ACTIVE_COMPARATOR

Entresto

Intervention Type: DRUG

First line therapy in Entresto arm

Valsartan

Intervention Type: DRUG

First line therapy in "usual meds" arm

Usual meds

First-line anti-hypertensive: valsartan, starting at 40 mg twice daily, increasing to a maximum dose of 160 mg twice daily

Group Type: ACTIVE_COMPARATOR

Entresto

Intervention Type: DRUG

First line therapy in Entresto arm

Valsartan

Intervention Type: DRUG

First line therapy in "usual meds" arm

Interventions

Entresto

First line therapy in Entresto arm

Intervention Type: DRUG

Valsartan

First line therapy in "usual meds" arm

Intervention Type: DRUG

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medtronic

INDUSTRY

Sponsor Role: collaborator

University of Maryland, Baltimore

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Van-Khue Ton, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University of Maryland

Other Identifiers

HP-00076889

Identifier Type: -

Identifier Source: org_study_id