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Sacubitril/Valsartan in Left Ventricular Assist Device Recipients

Phase 4
Active, not recruiting
Conditions
Heart Failure
Interventions
Drug: Sacubitril-Valsartan
Drug: Standard of care
Registration Number
NCT04103554
Lead Sponsor
University of Zagreb
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).

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
60
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

  4. 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

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
sacubitril/valsartanSacubitril-Valsartan-
Standard of careStandard of careStandard of care for treating blood pressure per center protocols
Primary Outcome Measures
NameTimeMethod
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 hypotension3 months

* End-stage renal disease defined as one of the following:

1. Initiation of dialysis (e.g., hemodialysis, peritoneal dialysis, or continuous venovenous hemodialysis), continuing for ≥ 20 days without known recovery of renal function

2. Initiation of dialysis with death before 30 days (excludes dialysis events associated with acute kidney injury with death before 30 days)

3. A drop in eGFR from baseline (randomization, i.e. Visit 101) to a value \<15 mL/min/1.73m2 on two consecutive measurements separated by≥ 20 days

4. Occurrence of kidney transplantation

* 50% sustained decline in eGFR: 50% decline from baseline (Randomization, Visit 101) as determined by 2 consecutive post-baseline measurements separated by ≥ 20 days

* Hyperkalemia: serum potassium ≥6.0 mmol/L \[mEq/L\]) Hypotension: symptomatic reduction in blood pressure requiring withdrawal of study medication or any BP lowering medication

Secondary Outcome Measures
NameTimeMethod
Change in Burden of hemocompatibility (hemocompatibility score)3 months, 12 months
Number of RV failure events3 months, 12 months
Time to first unplanned hospitalisation3 months, 12 months
Number of unplanned hospitalizations3 months, 12 months
Change in blood-pressure lowering medications3 months, 12 months
Change in eGFR values3 months, 12 months
Change in NT-proBNP from enrolment to 8 weeks8 weeks

Trial Locations

Locations (6)

University Hospital Centre Zagreb

🇭🇷

Zagreb, Croatia

IKEM

🇨🇿

Praha, Czechia

University Hospital Dubrava

🇭🇷

Zagreb, Croatia

Erasmus Medical Centre

🇳🇱

Rotterdam, Netherlands

University Medical Centre Utrecht

🇳🇱

Utrecht, Netherlands

John Paul II Hospital

🇵🇱

Kraków, Poland

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