Recruiting

ARNI

Sponsor:

The Cleveland Clinic

Code:

NCT04191681

Conditions

Stage D Heart Failure

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Sacubitril-Valsartan

Usual care (standard-of-care) arm

Study Details

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.

Conditions

Stage D Heart Failure

Study ID

NCT04191681

Start date

Nov 8, 2019

Status verified date

Jun, 2021

Completion date

Dec, 2022

Anticipated

Primary completion date

Mar, 2022

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

50 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Sacubitril-valsartan study arm

1. Start medication-naïve patients on low-dose sacubitril-valsartan (24/26 mg PO BID) without a washout period per guideline and label recommendations.
2. 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).
3. 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.
4. Sacubitril-valsartan can be up-titrated every 2-4 weeks per standard practice guidelines per physician's discretion as above.

active comparator: Usual care (standard-of-care) arm

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.

Interventions

Sacubitril-Valsartan

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.

Usual care (standard-of-care) arm

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

  • 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 ]
  • 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 ]

Central Contacts and Locations

Central contacts

Jerry D Estep, MD

216-444-7646estepj@ccf.org

Locations

Cleveland Clinic

Recruiting

Cleveland, Ohio, United States, 44195

Contacts

Jerry Estep, M. D.

216-444-7646estepj@ccf.org

More Information

Sponsor

The Cleveland Clinic

Last update posted

Jun 7, 2021

Last verified

Jun, 2021

Keywords

  • continuous flow left ventricular assist device
  • sacubitril-valsartan
  • oral vasodilator
  • Heart failure

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by The Cleveland Clinic on 2021-06-07.