Clinical trial NCT04191681: Safety and Efficacy of ARNI After LVAD ImplanT (SEAL-IT) Study
Official title: Safety and Efficacy of Angiotensin Receptor-neprilysin Inhibitor After Left Ventricular Assist Device ImplanT (SEAL-IT) Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Stage D Heart Failure
Keywords: continuous flow left ventricular assist device
sacubitril-valsartan
oral vasodilator
Heart failure
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
First posted: 2019-12-10
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate how well tolerated and effective an angiotensin receptor-neprilysin inhibitor (sacubitril-valsartan) is in patients with contemporary durable continuous flow left ventricular assist device (CF-LVAD) implantation compared to usual care oral vasodilator therapy.

Detailed description: The aim of this pilot study is to prospectively determine the short-term (at 3 months) and long-term (at 6 and 12 months) safety and efficacy of an angiotensin receptor-neprilysin inhibitor (sacubitril-valsartan) in patients with contemporary durable continuous flow left ventricular assist device (CF-LVAD) implantation compared to standard-of-care (usual care) oral vasodilator therapy.

Eligibility criteria: Inclusion Criteria:

1. Adults (age ≥ 18 years)
2. Durable CF-LVAD for any indication
3. NYHA II to IV classification
4. LVEF \< 40%
5. Written informed consent

Exclusion Criteria:

1. Inability to comply with the conditions of the protocol
2. Any patient with durable CF-LVAD who has any one of the following:

   i. symptomatic hypotension or MAP \< 60 mm Hg at randomization,

   ii. eGFR \< 30 mL/min/1.73 m2 at randomization,

   iii. potassium \> 5.4 mM at randomization,

   iv. history of angioedema at randomization,

   v. history of unacceptable side effects with ACE inhibitor, ARB, or sacubitril-valsartan therapy at randomization,

   vi. use of vasoactive agents (e.g., dobutamine, dopamine, epinephrine, norepinephrine, phenylephrine, vasopressin, nitroglycerin, nitroprusside, epoprostenol) or parenteral diuretics in 24 hours preceding randomization.

Primary outcomes:
measure: Incidence of drug discontinuation from drug-related adverse events due to sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 3 months
timeFrame: 3 months
measure: Time-averaged proportional change in NT-proBNP concentration (pg/mL) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 3 months
timeFrame: 3 months
Secondary outcomes:
measure: Time-averaged proportional change in NT-proBNP concentration (pg/mL) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 and 12 months
timeFrame: 6 and 12 months
measure: Proportion of patients (%) with effective MAP control (65 to 85 mm Hg) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 3, 6 and 12 months
timeFrame: 3, 6 and 12 months
measure: Proportion of patients (%) on other cardiac medications with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 3, 6 and 12 months relative to baseline
timeFrame: 3, 6 and 12 months
measure: Proportion of patients (%) in each New York Heart Association (NYHA) classification with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 3, 6 and 12 months relative to baseline
timeFrame: 3, 6 and 12 months
measure: Proportion of patients (%) with heart failure readmissions with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 and 12 months
timeFrame: 6 and 12 months
measure: Absolute change in mean left ventricular end-diastolic dimension (mm) on echocardiogram with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
timeFrame: 6 weeks and/or 3, 6 and/or 12 months
measure: Absolute change in mitral E/A ratio on echocardiogram with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
timeFrame: 6 weeks and/or 3, 6 and/or 12 months
measure: Absolute change in indexed left atrial volume (mL/m2) on echocardiogram with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
timeFrame: 6 weeks and/or 3, 6 and/or 12 months
measure: Absolute change in indexed right atrial volume (mL/m2) on echocardiogram with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
timeFrame: 6 weeks and/or 3, 6 and/or 12 months
measure: Absolute change in mean right atrial pressure (mm Hg) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
timeFrame: 6 weeks and/or 3, 6 and/or 12 months
measure: Absolute change in mean pulmonary artery pressure (mm Hg) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
timeFrame: 6 weeks and/or 3, 6 and/or 12 months
measure: Absolute change in mean pulmonary artery diastolic pressure (mm Hg) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
timeFrame: 6 weeks and/or 3, 6 and/or 12 months
measure: Absolute change in mean pulmonary capillary wedge pressure (mm Hg) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
timeFrame: 6 weeks and/or 3, 6 and/or 12 months
measure: Absolute change in pulmonary artery pulsatility index with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
timeFrame: 6 weeks and/or 3, 6 and/or 12 months
measure: Absolute change in pulmonary vascular resistance (Woods Unit) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
timeFrame: 6 weeks and/or 3, 6 and/or 12 months
measure: Absolute change in systemic vascular resistance (dynes-sec/cm5) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
timeFrame: 6 weeks and/or 3, 6 and/or 12 months
measure: Absolute change in cardiac index (L/min/m2) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
timeFrame: 6 weeks and/or 3, 6 and/or 12 months
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Jerry D Estep, MD
role: PRINCIPAL_INVESTIGATOR
References:
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