Angiotensin-Neprilysin Inhibition in Hemodialysis Initiation

• Status: Not yet recruiting
• Trial end date: 2025-07-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Brigham and Women's Hospital
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Treatments: Sacubitril and valsartan sodium hydrate drug combination; Valsartan

Criteria

Inclusion Criteria:

• 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 Criteria:

• 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.