Sacubitril-valsartan Versus Usual Anti-hypertensives in LVAD

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03279861
Recruitment Status : Withdrawn (protocol change)
First Posted : September 12, 2017
Last Update Posted : February 5, 2018
Information provided by (Responsible Party):
Van-Khue Ton, University of Maryland

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 Type : Interventional  (Clinical Trial)
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
Estimated Study Start Date : November 2017
Estimated Primary Completion Date : November 2018
Estimated Study Completion Date : November 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Valsartan

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

Primary Outcome Measures :
  1. Time spent with MAP < 85 mmHg [ Time Frame: 2 months ]
    Daily mean arterial pressure (MAP) < 85 mmHg

Secondary Outcome Measures :
  1. Number of drugs [ Time Frame: 2 months ]
    Number of anti-hypertensive drugs needed to achieve MAP < 85 mmHg

  2. Pump flow [ Time Frame: 2 months ]
    Correlation of pump flow with daily MAP

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03279861

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

Responsible Party: Van-Khue Ton, Assistant Professor of Medicine, University of Maryland Identifier: NCT03279861     History of Changes
Other Study ID Numbers: HP-00076889
First Posted: September 12, 2017    Key Record Dates
Last Update Posted: February 5, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Antihypertensive Agents
LCZ 696
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action