RecruitingPhase 2NCT05498181

Angiotensin-Neprilysin Inhibition in Hemodialysis Initiation

Sponsor

Brigham and Women's Hospital

Enrollment

100 participants

Start Date

Oct 11, 2022

Study Type

INTERVENTIONAL

Conditions

Hemodialysis

Summary

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.

Eligibility

Min Age: 18 Years

Inclusion Criteria5

Adults ≥18 years initiating HD (within 90 days of first HD session)
Thrice-weekly HD
Informed consent
Hemodynamically Stable: Sitting pre-dialysis SBP ≥110 mmHg averaged over prior two weeks or at the baseline visit; no symptomatic hypotension in prior two weeks; no use of midodrine.
Has not taken an ACEi for 36 hours prior to randomization

Exclusion Criteria21

Anuria (daily urine volume <100 mL/day)
Current or any use of sacubitril/valsartan within the past 30 days
History of hypersensitivity or intolerance to any of the study drugs, including ARBs or sacubitril/valsartan
Angioedema related to previous ACE inhibitor, ARB, or ARNI therapy
Serum potassium >5.5 mEq/L at screening (pre-HD if already on HD)
Acute coronary syndrome, stroke, TIA, major CV surgery, percutaneous coronary intervention or carotid angioplasty within one month
Intended coronary or carotid revascularization within 4 months
Implantation of a cardiac resynchronization therapy device (CRTD) within 3 months or intent to implant a CRTD
History of heart transplant, or planned heart transplant, or with left ventricular assist device
Planned renal transplant within 4 months
Documented untreated ventricular arrhythmia with syncopal episodes within 3 months
Symptomatic bradycardia or 2nd or 3rd degree heart block without a pacemaker
Presence of hemodynamically significant valvular disease or hypertrophic cardiomyopathy or infiltrative cardiomyopathy including suspected or confirmed amyloid heart disease (amyloidosis)
History of malignancy of any organ system within the past year (exceptions: squamous and basal cell carcinomas of the skin and carcinoma of the cervix in situ, or a malignancy that in the opinion of the investigator is considered cured with minimal risk of recurrence)
Liver disease (e.g., acute hepatitis, chronic active hepatitis, cirrhosis with evidence of portal hypertension); Alanine aminotransferase (ALT) levels >2.0 times the upper limit of normal (ULN) or total bilirubin >1.5 times the ULN, unless consistent with Gilbert's disease
Pregnant (positive hCG test) or lactating women
Enrollment in another interventional trial
Received an active investigational drug (including vaccines) other than a placebo agent, or used an investigational medical device within 12 weeks before Day 1/baseline
Does not have capacity to consent (Folstein mini-mental score of 23 or less)
Any condition that in the opinion of the investigator would make participation not in the best interest of the subject
Women of child-bearing age, unless using two birth control methods. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of investigational drug and for 7 days off of study drug.