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

Primary Purpose

Stage D Heart Failure

Status
Unknown status
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Sacubitril-Valsartan
Usual care (standard-of-care) arm
Sponsored by
The Cleveland Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stage D Heart Failure focused on measuring continuous flow left ventricular assist device, sacubitril-valsartan, oral vasodilator, Heart failure

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Cleveland ClinicRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Sacubitril-valsartan study arm

Usual care (standard-of-care) arm

Arm Description

Start medication-naïve patients on low-dose sacubitril-valsartan (24/26 mg PO BID) without a washout period per guideline and label recommendations. Switch patients to equivalent dose sacubitril-valsartan if on prior ACE inhibitor (after a 36 hour washout period) or ARB therapy (after discontinuing one day prior). If therapeutic range MAP (65 to 85 mm Hg), discontinue other oral vasodilator (e.g., hydralazine, isordil) or non-rate limiting dihydropyridine calcium channel blocker (non-DHP CCB, e.g., amlodipine) therapy on the day prior to sacubitril-valsartan initiation. If MAP > 85 mm Hg, low-dose sacubitril-valsartan will be added with or without discontinuation of other oral vasodilator or non-DHP CCB per physician's discretion based on drug tolerability and maintenance of therapeutic range MAP. Sacubitril-valsartan can be up-titrated every 2-4 weeks per standard practice guidelines per physician's discretion as above.

1. Continue current regimen of patients on oral vasodilator therapy (e.g., ACE inhibitor, ARB, hydralazine, isordil), allowing for up-titration of the drug every 2-4 weeks per standard practice guidelines in keeping with physician's discretion as above. 2. Start medication-naïve patients de novo on one of the oral vasodilators as below per guideline and label recommendations, allowing for up-titration of the drug every 2-4 weeks per standard practice guidelines in keeping with physician's discretion as above: i. ACE inhibitor: Enalapril 2.5 mg PO BID or Lisinopril 5 mg PO daily; ii. ARB: Valsartan 20 mg PO BID or Losartan 25 mg PO daily; iii. Other: Hydralazine 10 mg PO TID or Isordil 5 mg PO TID.

Outcomes

Primary Outcome Measures

Incidence of drug discontinuation from drug-related adverse events due to sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 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.
Time-averaged proportional change in NT-proBNP concentration (pg/mL) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 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 Outcome Measures

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

Full Information

First Posted
November 18, 2019
Last Updated
June 4, 2021
Sponsor
The Cleveland Clinic
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1. Study Identification

Unique Protocol Identification Number
NCT04191681
Brief Title
Safety and Efficacy of ARNI After LVAD ImplanT (SEAL-IT) Study
Acronym
SEAL-IT
Official Title
Safety and Efficacy of Angiotensin Receptor-neprilysin Inhibitor After Left Ventricular Assist Device ImplanT (SEAL-IT) Study
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Unknown status
Study Start Date
November 8, 2019 (Actual)
Primary Completion Date
March 2022 (Anticipated)
Study Completion Date
December 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Cleveland Clinic

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage D Heart Failure
Keywords
continuous flow left ventricular assist device, sacubitril-valsartan, oral vasodilator, Heart failure

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Sacubitril-valsartan study arm
Arm Type
Experimental
Arm Description
Start medication-naïve patients on low-dose sacubitril-valsartan (24/26 mg PO BID) without a washout period per guideline and label recommendations. Switch patients to equivalent dose sacubitril-valsartan if on prior ACE inhibitor (after a 36 hour washout period) or ARB therapy (after discontinuing one day prior). If therapeutic range MAP (65 to 85 mm Hg), discontinue other oral vasodilator (e.g., hydralazine, isordil) or non-rate limiting dihydropyridine calcium channel blocker (non-DHP CCB, e.g., amlodipine) therapy on the day prior to sacubitril-valsartan initiation. If MAP > 85 mm Hg, low-dose sacubitril-valsartan will be added with or without discontinuation of other oral vasodilator or non-DHP CCB per physician's discretion based on drug tolerability and maintenance of therapeutic range MAP. Sacubitril-valsartan can be up-titrated every 2-4 weeks per standard practice guidelines per physician's discretion as above.
Arm Title
Usual care (standard-of-care) arm
Arm Type
Active Comparator
Arm Description
1. Continue current regimen of patients on oral vasodilator therapy (e.g., ACE inhibitor, ARB, hydralazine, isordil), allowing for up-titration of the drug every 2-4 weeks per standard practice guidelines in keeping with physician's discretion as above. 2. Start medication-naïve patients de novo on one of the oral vasodilators as below per guideline and label recommendations, allowing for up-titration of the drug every 2-4 weeks per standard practice guidelines in keeping with physician's discretion as above: i. ACE inhibitor: Enalapril 2.5 mg PO BID or Lisinopril 5 mg PO daily; ii. ARB: Valsartan 20 mg PO BID or Losartan 25 mg PO daily; iii. Other: Hydralazine 10 mg PO TID or Isordil 5 mg PO TID.
Intervention Type
Drug
Intervention Name(s)
Sacubitril-Valsartan
Other Intervention Name(s)
Entresto
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Usual care (standard-of-care) arm
Other Intervention Name(s)
Oral Vasodilator
Intervention Description
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.
Primary Outcome Measure Information:
Title
Incidence of drug discontinuation from drug-related adverse events due to sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 3 months
Description
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.
Time Frame
3 months
Title
Time-averaged proportional change in NT-proBNP concentration (pg/mL) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 3 months
Description
Time-averaged proportional change in NT-proBNP concentration (pg/mL) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 3 months.
Time Frame
3 months
Secondary Outcome Measure Information:
Title
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
Description
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.
Time Frame
6 and 12 months
Title
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
Description
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.
Time Frame
3, 6 and 12 months
Title
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
Description
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.
Time Frame
3, 6 and 12 months
Title
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
Description
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.
Time Frame
3, 6 and 12 months
Title
Proportion of patients (%) with heart failure readmissions with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 and 12 months
Description
Proportion of patients (%) with heart failure readmissions with sacubitril-valsartan versus standard-of-care oral vasodilator therapy determined at 6 and 12 months.
Time Frame
6 and 12 months
Title
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
Description
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.
Time Frame
6 weeks and/or 3, 6 and/or 12 months
Title
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
Description
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.
Time Frame
6 weeks and/or 3, 6 and/or 12 months
Title
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
Description
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.
Time Frame
6 weeks and/or 3, 6 and/or 12 months
Title
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
Description
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.
Time Frame
6 weeks and/or 3, 6 and/or 12 months
Title
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
Description
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.
Time Frame
6 weeks and/or 3, 6 and/or 12 months
Title
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
Description
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.
Time Frame
6 weeks and/or 3, 6 and/or 12 months
Title
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
Description
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.
Time Frame
6 weeks and/or 3, 6 and/or 12 months
Title
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
Description
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.
Time Frame
6 weeks and/or 3, 6 and/or 12 months
Title
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
Description
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.
Time Frame
6 weeks and/or 3, 6 and/or 12 months
Title
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
Description
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.
Time Frame
6 weeks and/or 3, 6 and/or 12 months
Title
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
Description
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.
Time Frame
6 weeks and/or 3, 6 and/or 12 months
Title
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
Description
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.
Time Frame
6 weeks and/or 3, 6 and/or 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jerry D Estep, MD
Phone
216-444-7646
Email
estepj@ccf.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jerry D Estep, MD
Organizational Affiliation
The Cleveland Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jerry Estep, M. D.
Phone
216-444-7646
Email
estepj@ccf.org

12. IPD Sharing Statement

Citations:
PubMed Identifier
30700139
Citation
Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, Chang AR, Cheng S, Das SR, Delling FN, Djousse L, Elkind MSV, Ferguson JF, Fornage M, Jordan LC, Khan SS, Kissela BM, Knutson KL, Kwan TW, Lackland DT, Lewis TT, Lichtman JH, Longenecker CT, Loop MS, Lutsey PL, Martin SS, Matsushita K, Moran AE, Mussolino ME, O'Flaherty M, Pandey A, Perak AM, Rosamond WD, Roth GA, Sampson UKA, Satou GM, Schroeder EB, Shah SH, Spartano NL, Stokes A, Tirschwell DL, Tsao CW, Turakhia MP, VanWagner LB, Wilkins JT, Wong SS, Virani SS; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2019 Update: A Report From the American Heart Association. Circulation. 2019 Mar 5;139(10):e56-e528. doi: 10.1161/CIR.0000000000000659. No abstract available. Erratum In: Circulation. 2020 Jan 14;141(2):e33.
Results Reference
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PubMed Identifier
25176015
Citation
McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014 Sep 11;371(11):993-1004. doi: 10.1056/NEJMoa1409077. Epub 2014 Aug 30.
Results Reference
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PubMed Identifier
30415601
Citation
Velazquez EJ, Morrow DA, DeVore AD, Duffy CI, Ambrosy AP, McCague K, Rocha R, Braunwald E; PIONEER-HF Investigators. Angiotensin-Neprilysin Inhibition in Acute Decompensated Heart Failure. N Engl J Med. 2019 Feb 7;380(6):539-548. doi: 10.1056/NEJMoa1812851. Epub 2018 Nov 11. Erratum In: N Engl J Med. 2019 Mar 14;380(11):1090.
Results Reference
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PubMed Identifier
31134724
Citation
Wachter R, Senni M, Belohlavek J, Straburzynska-Migaj E, Witte KK, Kobalava Z, Fonseca C, Goncalvesova E, Cavusoglu Y, Fernandez A, Chaaban S, Bohmer E, Pouleur AC, Mueller C, Tribouilloy C, Lonn E, A L Buraiki J, Gniot J, Mozheiko M, Lelonek M, Noe A, Schwende H, Bao W, Butylin D, Pascual-Figal D; TRANSITION Investigators. Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study. Eur J Heart Fail. 2019 Aug;21(8):998-1007. doi: 10.1002/ejhf.1498. Epub 2019 May 27.
Results Reference
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Safety and Efficacy of ARNI After LVAD ImplanT (SEAL-IT) Study

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