Angiotensin-Neprilysin Inhibition in Hemodialysis Initiation
Purpose
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.
Condition
- Hemodialysis
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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.
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Parallel group randomized trial of sacubitril/valsartan versus placebo
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
- Masking Description
- Blinded (quadruple) and placebo-controlled
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental sacubitril/valsartan |
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). |
|
|
Placebo Comparator placebo |
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). |
|
Recruiting Locations
Brigham and Women's
Boston, Massachusetts 02115
Boston, Massachusetts 02115
Contact:
Finnian Mc Causland
Finnian Mc Causland
More Details
- Status
- Recruiting
- Sponsor
- Brigham and Women's Hospital