Sacubitril-Valsartan for Hemodialysis Patients
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Brigham and Women's Hospital
Prior Safety Data
Approved in 3 jurisdictions
Trial Summary
What is the purpose of this trial?This randomized placebo-controlled clinical trial will evaluate the effect of sacubitril/valsartan (compared with placebo) on echocardiographic measures of hypervolemia, preservation of residual renal function, and key safety parameters in incident hemodialysis patients.
How is the drug sacubitril-valsartan unique for hemodialysis patients?
Sacubitril-valsartan is unique because it combines two components that work together to improve heart function and reduce blood pressure in hemodialysis patients, showing better results than using valsartan alone. It has been shown to improve heart function and reduce symptoms in patients with heart failure and hypertension undergoing dialysis, without causing common side effects like high potassium levels.
24679Is sacubitril-valsartan safe for humans?
Sacubitril-valsartan (Entresto) is generally safe for humans but can cause side effects like low blood pressure, swelling (angioedema), kidney problems, high potassium levels, low sodium levels, and in rare cases, liver injury. It should not be used during pregnancy, breastfeeding, or with certain other medications in people with diabetes.
12348What data supports the effectiveness of the drug sacubitril-valsartan for hemodialysis patients?
Research shows that sacubitril-valsartan can improve heart function and reduce blood pressure in hemodialysis patients with heart failure, as seen in improvements in heart measurements and symptoms over a 6-month period.
24579Will I have to stop taking my current medications?
The trial requires that you have not taken an ACE inhibitor for 36 hours before joining. If you are currently using sacubitril/valsartan, you must stop at least 30 days before participating. Other medications are not specifically mentioned, so it's best to discuss with the trial team.
Eligibility Criteria
Adults over 18 who recently started hemodialysis can join this trial. They must have stable blood pressure, not be on certain heart medications, and able to consent. Excluded are those with recent major heart issues, planned transplants, severe liver disease, untreated serious arrhythmias or cancer within the last year.Participant Groups
The trial tests if sacubitril-valsartan is better than a placebo for managing fluid overload and preserving kidney function in new hemodialysis patients. It's randomized: participants won't choose which treatment they get.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: sacubitril/valsartanExperimental Treatment1 Intervention
Participants will take sacubitril/valsartan, beginning dose of 24/26mg twice daily, with titration to target dose of 97/103 mg twice daily over the first four weeks. Patients will remain on the maximally tolerated dose for the remaining 12 weeks (total on-drug period of 16 weeks) before stopping drug and being followed for a further two weeks (total study time of 18 weeks).
Group II: placeboPlacebo Group2 Interventions
Participants will take equivalent placebo, beginning equivalent dose of 24/26mg twice daily, with titration to target equivalent dose of 97/103 mg twice daily over the first four weeks. Patients will remain on the maximally tolerated dose for the remaining 12 weeks (total on-drug period of 16 weeks) before stopping drug/placebo and being followed for a further two weeks (total study time of 18 weeks).
Sacubitril-valsartan is already approved in European Union, United States, Australia for the following indications:
🇪🇺 Approved in European Union as Entresto for:
- Heart failure with reduced ejection fraction
🇺🇸 Approved in United States as Entresto for:
- Chronic heart failure with reduced ejection fraction
🇦🇺 Approved in Australia as Entresto for:
- Heart failure with reduced ejection fraction
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Brigham and Women'sBoston, MA
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Who is running the clinical trial?
Brigham and Women's HospitalLead Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Collaborator
References
[Angiotensin-receptor- and neprilysin-inhibition: a new option against heart failure]. [2021]The molecular combination of sacubitril and valsartan (Entresto) is a new drug for reducing the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction. It is usually administered in conjunction with other heart failure therapies, instead of an ACE inhibitor or an angiotensin-receptor blocker (ARB). In studies, sacubitril/ valsartan was superior to enalapril in reducing the risks of death and hospitalization for heart failure. Possible side effects of sacubitril/valsartan are hypotension, angioedema, impaired renal function and elevation in serum potassium levels. The drug should not be used in times of pregnancy and breast feeding, in patients with servere hepatic impairment (Child-Pugh C) and in combination with aliskiren in patients with diabetes.
LCZ696 (Sacubitril/Valsartan), an Angiotensin-Receptor Neprilysin Inhibitor, Attenuates Cardiac Hypertrophy, Fibrosis, and Vasculopathy in a Rat Model of Chronic Kidney Disease. [2023]Chronic kidney disease (CKD) is associated with cardiac hypertrophy, fibrosis, and increased risk of cardiovascular mortality. LCZ696 (sacubitril/valsartan) is a promising agent that has shown significant potential in treatment of heart failure. We hypothesized that LCZ696 is more effective than valsartan alone in the treatment of cardiovascular abnormalities associated with experimental CKD.
Sacubitril/Valsartan (Entresto®)-Induced Hyponatremia. [2021]Sacubitril/valsartan (Entresto®) is the first commercially available angiotensin receptor neprilysin inhibitor (ARNI) approved for use in heart failure patients with a reduced ejection fraction. It is a combination drug that contains sacubitril, a neprilysin inhibitor, and valsartan, an angiotensin II receptor blocker. Our report outlines a case of probable ARNI-induced hyponatremia occurring in an elderly woman with heart failure with a reduced ejection fraction. According to Naranjo Adverse Drug Reaction Assessment, score indicated a likely association between patient's hyponatremia and her use of sacubitril/valsartan.
Sacubitril/valsartan in chronic kidney disease, the nephrologist point of view. [2021]Sacubitril/valsartan reduces cardiovascular morbidity and mortality in patients with systolic dysfunction. The aim of the present study was to assess the evolution of chronic kidney disease (CKD) patients after initiating sacubitril/valsartan.
Sacubitril/valsartan in heart failure and end-stage renal insufficiency. [2021]The aim of this report is to describe the feasibility and tolerability of medical treatment with sacubitril/valsartan in a patient treated with hemodialysis. We describe the case of a 67-year-old man with heart failure with reduced ejection fraction due to an ischemic cardiomyopathy and renal insufficiency undergoing hemodialysis. Because of worsening heart failure with no other therapeutic options, a treatment with sacubitril/valsartan was started. Although this patient had a very low systolic blood pressure, he could tolerate a moderate dose of 49/51 mg twice daily. After initiation of sacubitril/valsartan, there was a symptomatic improvement with a clear reduction NT-proBNP, accompanied by a decrease in filling pressures. In conclusion, in this patient with severe heart failure undergoing hemodialysis, treatment with sacubitril/valsartan was feasible, safe, and improved heart failure symptoms.
Pharmacokinetics and pharmacodynamics of sacubitril/valsartan in peritoneal dialysis patients. [2023]There is little information on the pharmacokinetics and pharmacodynamics of sacubitril/valsartan (SV) in patients undergoing peritoneal dialysis (PD) complicated with hypertension or heart failure (HF). This study was designed to evaluate the pharmacokinetics and pharmacodynamics of SV in PD patients with complications of hypertension or HF.
Effects of sacubitril-valsartan in the treatment of chronic heart failure patients with end-stage renal disease undergoing dialysis. [2023]The data on the effects of the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril-valsartan (LCZ696) in chronic heart failure (CHF) patients with end-stage renal disease (ESRD) requiring dialysis are lacking. This study assessed the efficacy and safety of LCZ696 in CHF patients with ESRD on dialysis.
Sacubitril/valsartan-induced liver injury: A case report and literature review. [2023]Sacubitril/valsartan (Entresto) is the first drug approved for the treatment of symptomatic chronic heart failure with reduced ejection fraction in adult patients. There have been no reports of hepatotoxicity secondary to sacubitril/valsartan administration. Here, we report the first case of severe liver injury caused by sacubitril/valsartan.
Functional changes in the heart after sacubitril/valsartan use in 5 hemodialysis patients with hypertension. Case report. [2023]The purpose of this report is to describe the efficacy of sacubitril/valsartan in 5 hemodialysis patients with hypertension, including a patient with heart failure with reduced ejection fraction (HFrEF) and a patient with preserved ejection fraction (HFpEF) focused on the functional changes in the heart. We switched from angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) to sacubitril/valsartan and compared blood pressure post dialysis, N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels and the findings of echocardiography for a period of 6 months. A month after the initiation of sacubitril/valsartan, there was improvement of symptoms and blood pressure post-dialysis, the NT-pro-BNP levels decreased from 23,132.2 ± 16,561.3 pg/mL to 8327 ± 3334.3 pg/mL, and the echocardiography findings showed a decrease in the left atrial dimension from 37.7 ± 5.7 mm to 33 ± 4.9 mm and an increase in the left ventricular ejection fraction from 58.2 ± 16.9% to 66.4 ± 15.0%. These results were sustained for up to 6 months. Also, blood pressure post-dialysis changed from 164 ± 11/77 mmHg to 150 ± 13/72 mmHg over the 6-month period. There were no side effects, such as hyperkalemia and lymphoedema. In conclusion, 5 patients had hypertension, including 2 patients with heart failure. Sacubitril/valsartan improved blood pressure post-dialysis, heart failure symptoms, NT-pro- BNP, the left atrial dimension, the left ventricular ejection fraction, and E/e', E/A found via echocardiography for a 6-months period. Treatment with sacubitril/valsartan was effective in hemodialysis patients in the cardiac function.