heart failure
Conditions
Interventions
The patients will be assigned to one of the following two treatment arms at
Visit 101.
• sacubitril/valsartan at dose levels 1 or 2 (24/26 mg or 49/51 mg twice daily,
first dose around 08:00 hours i
Sponsors
University of Zagreb School of Medicine
Eligibility
Age
18 Years to 99 Years
Inclusion 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
Exclusion criteria
Exclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary safety variable is time to first occurrence of all-cause death, or deterioration in renal function (defined as reaching end-stage renal disease, renal death or 50% sustained decline in eGFR), hyperkalemia or symptomatic hypotension leading to drug withdrawal during the active treatment period, based on the following: • End-stage renal disease defined as one of the following: a) Initiation of dialysis (e.g., hemodialysis, peritoneal dialysis, or continuous venovenous hemodialysis), continuing for >= 20 days without known recovery of renal function b) Initiation of dialysis with death before 30 days (excludes dialysis events associated with acute kidney injury with death before 30 days) c) A drop in eGFR from baseline (randomization, i.e. Visit 101) to a value = 20 days d) Occurrence of kidney transplantation • 50% sustained decline in eGFR: 50% decline from baseline (Randomization, Visit 101) as determined by 2 consecutive postbaseline 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 Time-to-event is computed as the number of days from randomization to the start date of the primary endpoint event (first occurrence of any of the above-mentioned outcomes). A patient without an event will be censored at the last date the endpoint status was completely known (this date could include the date of withdrawal of informed consent, date of the patient*s 3-month visit (whichever occurred first)), or at the date of heart transplant, should it occur. Kaplan-Meier and Cox regression analyses will be used for the assessment of the primary outcome, and based on the Safety population. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary efficacy variables, assessed from enrolment to 3 months and from enrolment to 12 months, unless stated differently are: • Change in NT-proBNP from enrolment to 8 weeks • Change in Burden of hemocompatibility (hemocompatibility score) • Number of RV failure events (as defined in section 2.2.) • Time to first unplanned hospitalisation • Number of unplanned hospitalizations • Change in blood-pressure lowering medications • Change in eGFR values The exploratory variables, assessed from enrolment to 3 months and from enrolment to 12 months, are: • Change in 6MWT • Change in Quality of Life related Symptoms assessed by KCCQ and EQ-5D • Non-surgical bleeding events: an episode of suspected internal or external bleeding that results in one or more of the following: a. Death, b. Reoperation, c. Hospitalization, d. Any transfusion of packed red blood cells (PRBC) (any transfusion of >= 2U PRBC will be considered a serious bleed) • Number of haemorrhagic stroke events • Number of de-novo AI occurrence • Change in markers of inflammation (change in high-sensitivity CRP) • Change in left ventricular size • Change in left ventricular volumes and ejection fraction • Change in left atrial volumes • Change in right ventricular size and function • Change in LVAD low-flow alarms • Change in PVC and atrial high rate burden in pacing device carriers In general, secondary and exploratory efficacy variables will be analyzed based on the randomised population. All statistical tests will be performed at the two-sided significance level of 0.05. To better satisfy the normality assumption, the log-transformation is performed on each biomarker for analysis. All continuous outcomes will be analysed using linear regression models adjusted for the corresponding baseline value, enrolment strata, and treatment assignment. Non-normally distributed biomarkers will be log-transformed prior to analysis and estimated treatment effects will be presented a | — |
Countries
Netherlands
Outcome results
None listed