Clinical trial NCT04103554: Sacubitril/Valsartan in Left Ventricular Assist Device Recipients
Official title: A Multicenter, Randomized, Open-label, Parallel Group, Pilot Study to Evaluate the Use of Sacubitril/Valsartan in HeartMate 3 LVAD Recipients
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Heart Failure
Keywords: LVAD (Left Ventricular Assist Device)
sacubitril/valsartan
heart failure
Lead sponsor: University of Zagreb
Sponsor class: OTHER
First posted: 2019-09-25
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: Inclusion Criteria:

1. Written informed consent must be obtained before any assessment is performed.
2. ≥18 years of age, male or female
3. Recently implanted HeartMate 3 LVAD recipients, in stable condition and deemed ready for discharge or chronic, stable, ambulatory HeartMate 3 LVAD carriers implanted within 1 year prior to enrolment

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

Primary outcomes:
measure: 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
timeFrame: 3 months
Secondary outcomes:
measure: Change in NT-proBNP from enrolment to 8 weeks
timeFrame: 8 weeks
measure: Change in Burden of hemocompatibility (hemocompatibility score)
timeFrame: 3 months, 12 months
measure: Number of RV failure events
timeFrame: 3 months, 12 months
measure: Time to first unplanned hospitalisation
timeFrame: 3 months, 12 months
measure: Number of unplanned hospitalizations
timeFrame: 3 months, 12 months
measure: Change in blood-pressure lowering medications
timeFrame: 3 months, 12 months
measure: Change in eGFR values
timeFrame: 3 months, 12 months
Other outcomes:
Locations:
city: Zagreb
country: Croatia
facility: University Hospital Centre Zagreb
city: Zagreb
country: Croatia
facility: University Hospital Dubrava
city: Praha
country: Czechia
facility: IKEM
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Centre
city: Utrecht
country: Netherlands
facility: University Medical Centre Utrecht
city: Kraków
country: Poland
facility: John Paul II Hospital
Study officials:
affiliation: University of Zagreb School of Medicine
name: Maja Cikes, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: