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The primary objective of this prospective randomised study is to assess the safety and tolerability of sacubitril/valsartan compared with standard of care used for treating BP in patients that have been implanted with the Heart Mate 3 LVAD (events of special interest - all cause death, right ventricular failure, bleeding events, deterioration in renal function, hyperkalemia, symptomatic hypotension).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| sacubitril/valsartan | Experimental |
| |
| Standard of care | Active Comparator | Standard of care for treating blood pressure per center protocols |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sacubitril-Valsartan | Drug | Sacubitril-Valsartan 24/26 mg BID, 49/51 mg BID, 97/103 mg BID |
|
| Measure | Description | Time Frame |
|---|---|---|
| Freedom from all-cause death, deterioration in renal function (reaching end-stage renal disease (ESRD), renal death or 50% decline in eGFR), hyperkalemia or symptomatic hypotension |
| 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in NT-proBNP from enrolment to 8 weeks | 8 weeks | |
| Change in Burden of hemocompatibility (hemocompatibility score) | 3 months, 12 months | |
| Number of RV failure events |
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Inclusion Criteria:
1. Current acute decompensated HF (including right ventricular failure) requiring therapy with intravenous diuretics or vasodilators and/or inotropic drugs within the past 48 hours 2. History of hypersensitivity to sacubitril/valsartan or to drugs of similar chemical classes, patients with a known history of angioedema 3. Patients with mean blood pressure ≤75 mmHg (systolic blood pressure i.e. Doppler opening blood pressure ≤90 mmHg in those pulsatile and measured by Doppler method) or symptomatic hypotension 4. eGFR < 30 mL/min/1.73m2 as calculated by the Modification in Diet in Renal Disease (MDRD) formula at Visit 1 5. Patients with serum potassium >5.4 mmol/L (mEq/L) at Visit 1 6. Hemodynamically unstable patients or those with ongoing MCS other than LVAD or those with planned biventricular support 7. Hemodynamically significant aortic insufficiency in the opinion of the investigator 8. Irreversible end-organ dysfunction 9. Previous sacubitril/valsartan use while on LVAD support 10. Acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or other major CV surgery, percutaneous coronary intervention (PCI) or carotid angioplasty within 30 days prior to enrolment 11. Life-threatening or uncontrolled dysrhythmia, including symptomatic or sustained ventricular tachycardia and atrial fibrillation or flutter with a resting ventricular rate >110 bpm at enrolment 12. Any surgical or medical condition, which in the opinion of the Investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study 13. Active infection with hemodynamic compromise 14. hemoglobin (Hgb) <8 g/dl 15. body mass index (BMI) > 45 kg/m2 16. Congenital heart disease 17. Coronary or carotid artery disease or valvular heart disease likely to require surgical or percutaneous intervention within the 6 months after enrolment 18. Evidence of hepatic disease as determined by any one of the following: SGOT (AST) or SGPT (ALT) values exceeding 3x ULN, bilirubin >1.5 mg/dl at Visit 1 19. Pregnant or nursing (lactating) women and women of child-bearing potential unless they are using highly effective methods of contraception
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| Name | Affiliation | Role |
|---|---|---|
| Maja Cikes, MD, PhD | University of Zagreb | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Centre Zagreb | Zagreb | 10000 | Croatia | |||
| University Hospital Dubrava |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40818766 | Derived | Cikes M, Planinc I, Brugts JJ, Claggett B, Jorde UP, Milicic D, Ruschitzka F, Uriel N, Jakus N, Loncaric F, Puskaric F, Rubis P, van Laake LW, Rudez I, Hegarova M, Mehra M, Solomon SD. Rationale, design, and baseline characteristics of the multicENter, randomized, open-label, parallel group, study to evaluate the use of sacubitril/valsartan in HeartMate 3 left ventricular assist device recipients (ENVAD-HF). J Card Fail. 2026 Feb;32(2):406-418. doi: 10.1016/j.cardfail.2025.07.015. Epub 2025 Aug 14. |
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| ID | Term |
|---|---|
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| C549068 | sacubitril and valsartan sodium hydrate drug combination |
| D059039 | Standard of Care |
| ID | Term |
|---|---|
| D019984 | Quality Indicators, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
| D017530 | Health Care Quality, Access, and Evaluation |
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| Standard of care | Drug | standard of care used for treating BP |
|
| 3 months, 12 months |
| Time to first unplanned hospitalisation | 3 months, 12 months |
| Number of unplanned hospitalizations | 3 months, 12 months |
| Change in blood-pressure lowering medications | 3 months, 12 months |
| Change in eGFR values | 3 months, 12 months |
| Zagreb |
| 10000 |
| Croatia |
| IKEM | Prague | Czechia |
| Erasmus Medical Centre | Rotterdam | 3015 GD | Netherlands |
| University Medical Centre Utrecht | Utrecht | Netherlands |
| John Paul II Hospital | Krakow | Poland |