Clinical trial NCT03279861: Sacubitril-valsartan Versus Usual Anti-hypertensives in LVAD
Official title: Sacubitril-valsartan (Entresto) Versus Standard Anti-hypertensive Therapy in LVAD Patients - A Feasibility Pilot Study
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Congestive Heart Failure
Hypertension
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: Medtronic
First posted: 2017-09-12
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Time spent with MAP < 85 mmHg
timeFrame: 2 months
Secondary outcomes:
measure: Number of drugs
timeFrame: 2 months
measure: Pump flow
timeFrame: 2 months
Other outcomes:
Locations:
Study officials:
affiliation: University of Maryland
name: Van-Khue Ton, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: