Sacubitril-valsartan Versus Usual Anti-hypertensives in LVAD

Sponsor

University of Maryland (Other)

Overall Status

Withdrawn

CT.gov ID

NCT03279861

Collaborator

Medtronic (Industry)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Congestive Heart Failure Hypertension	Drug: Entresto Drug: Valsartan	Phase 4

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Nov 1, 2017

Anticipated Primary Completion Date :

Nov 1, 2018

Anticipated Study Completion Date :

Nov 1, 2019

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Time spent with MAP < 85 mmHg [2 months]
Daily mean arterial pressure (MAP) < 85 mmHg

Secondary Outcome Measures

Number of drugs [2 months]
Number of anti-hypertensive drugs needed to achieve MAP < 85 mmHg
Pump flow [2 months]
Correlation of pump flow with daily MAP

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

University of Maryland
Medtronic

Investigators

Principal Investigator: Van-Khue Ton, MD PhD, University of Maryland

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Van-Khue Ton, Assistant Professor of Medicine, University of Maryland

ClinicalTrials.gov Identifier:

NCT03279861

Other Study ID Numbers:

HP-00076889

First Posted:

Sep 12, 2017

Last Update Posted:

Feb 5, 2018

Last Verified:

Feb 1, 2018

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Heart Failure

Valsartan

Sacubitril and valsartan sodium hydrate drug combination

Study Results

No Results Posted as of Feb 5, 2018