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

NeuroTherapia, Inc.

Status and phase: Unknown; Phase 4

Conditions: Stage D Heart Failure

Treatments: Drug: Usual care (standard-of-care) arm; Drug: Sacubitril-Valsartan

Study type: Interventional

Funder types: Other

Identifiers

NCT04191681

19-1132

Details and patient eligibility

About

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.

Full 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.

Enrollment: 50 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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50 participants in 2 patient groups

Sacubitril-valsartan study arm

Experimental group

Description:

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.

Treatment:

Drug: Sacubitril-Valsartan

Usual care (standard-of-care) arm

Active Comparator group

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.

Treatment:

Drug: Usual care (standard-of-care) arm