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NCT Number: NCT04191681

Safety and Efficacy of ARNI After LVAD ImplanT (SEAL-IT) Study

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.

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Key information

Conditions

Stage D Heart Failure Cardiovascular Diseases Heart Diseases Heart Failure

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location status: Recruiting

Location contact

Jerry Estep, M. D.

CONTACT

[email protected]

216-444-7646

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Adults (age ≥ 18 years)
  • Durable CF-LVAD for any indication
  • NYHA II to IV classification
  • LVEF < 40%
  • Written informed consent

Exclusion criteria

  • Inability to comply with the conditions of the protocol
  • 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.

Treatment and study plan

Sacubitril-valsartan

Drug

Sacubitril-valsartan at low or equivalent dose to be initiated or added to patients randomized to this arm, and titrated up every 2-4 weeks, per standard practice guidelines and label recommendations per physician's discretion.

Other names: Entresto

Usual care (standard-of-care) arm

Drug

Other oral vasodilator therapy to be continued or initiated to patients randomized to this arm, and titrated up every 2-4 weeks, per standard practice guidelines and label recommendations per physician's discretion.

Other names: Oral Vasodilator

Primary outcomes

  1. Incidence of drug discontinuation from drug-related adverse events due to sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 3 months

    Time frame: 3 months

    Incidence of drug discontinuation from drug-related adverse events due to sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 3 months. Incidence of drug discontinuation is defined as the number of patients exposed to the drug with an adverse event over the total number of patients exposed to the drug. An adverse event is defined as any one of the following: acute kidney injury with eGFR decline > 25% from baseline, hyperkalemia with potassium > 5.5 mM, hypotension with mean arterial pressure (MAP) < 60 mm Hg, angioedema, dizziness, and/or cough.

  2. Time-averaged proportional change in NT-proBNP concentration (pg/mL) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 3 months

    Time frame: 3 months

    Time-averaged proportional change in NT-proBNP concentration (pg/mL) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 3 months.

Secondary outcomes

  1. 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

    Time frame: 6 and 12 months

    Time-averaged proportional change in NT-proBNP concentration (pg/mL) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 6 and 12 months.

  2. 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

    Time frame: 3, 6 and 12 months

    Proportion of patients (%) with effective MAP control (65 to 85 mm Hg) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 3, 6 and 12 months.

  3. 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

    Time frame: 3, 6 and 12 months

    Proportion of patients (%) on other cardiac medications (e.g., diuretics, aldosterone antagonists, beta-blockers, oral vasodilators, and anti-hypertensives) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 3, 6 and 12 months relative to baseline.

  4. 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

    Time frame: 3, 6 and 12 months

    Proportion of patients (%) in each New York Heart Association (NYHA) classification (e.g., functional class I-IV) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 3, 6 and 12 months relative to baseline.

  5. Proportion of patients (%) with heart failure readmissions with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 and 12 months

    Time frame: 6 and 12 months

    Proportion of patients (%) with heart failure readmissions with sacubitril-valsartan versus standard-of-care oral vasodilator therapy determined at 6 and 12 months.

  6. 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

    Time frame: 6 weeks and/or 3, 6 and/or 12 months

    Absolute change in mean left ventricular end-diastolic dimension (mm) on echocardiogram with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 6 weeks and/or 3, 6 and/or 12 months.

  7. 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

    Time frame: 6 weeks and/or 3, 6 and/or 12 months

    Absolute change in mitral E/A ratio on echocardiogram with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 6 weeks and/or 3, 6 and/or 12 months.

  8. 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

    Time frame: 6 weeks and/or 3, 6 and/or 12 months

    Absolute change in indexed left atrial volume (mL/m2) on echocardiogram with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 6 weeks and/or 3, 6 and/or 12 months.

  9. 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

    Time frame: 6 weeks and/or 3, 6 and/or 12 months

    Absolute change in indexed right atrial volume (mL/m2) on echocardiogram with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 6 weeks and/or 3, 6 and/or 12 months.

  10. 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

    Time frame: 6 weeks and/or 3, 6 and/or 12 months

    Absolute change in mean right atrial pressure (mm Hg) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 6 weeks and/or 3, 6 and/or 12 months.

  11. 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

    Time frame: 6 weeks and/or 3, 6 and/or 12 months

    Absolute change in mean pulmonary artery pressure (mm Hg) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 6 weeks and/or 3, 6 and/or 12 months.

  12. 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

    Time frame: 6 weeks and/or 3, 6 and/or 12 months

    Absolute change in mean pulmonary artery diastolic pressure (mm Hg) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 6 weeks and/or 3, 6 and/or 12 months.

  13. 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

    Time frame: 6 weeks and/or 3, 6 and/or 12 months

    Absolute change in mean pulmonary capillary wedge pressure (mm Hg) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 6 weeks and/or 3, 6 and/or 12 months.

  14. 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

    Time frame: 6 weeks and/or 3, 6 and/or 12 months

    Absolute change in pulmonary artery pulsatility index with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 6 weeks and/or 3, 6 and/or 12 months.

  15. 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

    Time frame: 6 weeks and/or 3, 6 and/or 12 months

    Absolute change in pulmonary vascular resistance (Woods Unit) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 6 weeks and/or 3, 6 and/or 12 months.

  16. 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

    Time frame: 6 weeks and/or 3, 6 and/or 12 months

    Absolute change in systemic vascular resistance (dynes-sec/cm5) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 6 weeks and/or 3, 6 and/or 12 months.

  17. 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

    Time frame: 6 weeks and/or 3, 6 and/or 12 months

    Absolute change in cardiac index (L/min/m2) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 6 weeks and/or 3, 6 and/or 12 months.

Study contacts

Contact information is provided by the study sponsor or research team.

Jerry D Estep, MD

CONTACT

[email protected]

216-444-7646

Sponsors and collaborators

Lead sponsor

The Cleveland Clinic

Other

Registry information

Official study title

Safety and Efficacy of Angiotensin Receptor-neprilysin Inhibitor After Left Ventricular Assist Device ImplanT (SEAL-IT) Study

Acronym: SEAL-IT

Important dates

Study start
2019
Primary completion
2022
Study completion
2022
First posted
Dec 10, 2019
Registry last updated
Jun 7, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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