Effect of changing angiotensin receptor blocker into "angiotensin receptor-neprilysin inhibitor" on out-of-office blood pressures in hypertensive patients with chronic kidney disease stage G4-5

JRCT ID: jRCT1031220149

Registered date:21/06/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Hypertensive patients with CKD stage G4-to-G5
• Date of first enrollment: 21/06/2022
• Target sample size: 30
• Study type: Interventional

Intervention(s)

Administration of sacubitril/valsartan 100mg daily will be performed instead of ARB participants are using.
At 4 (+/-2) weeks after sacubitril/valsartan administration, the dose of sacubitril/valsartan can be increased to 200mg daily, if the blood pressures of participants do not achieve the target blood pressure levels, and adverse events (such as acute kidney injury, or hyperkalemia) do not occur. The dose of sacubitril/valsartan will be administered to participants for 8 (+/-2) weeks.

Outcome(s)

• Primary Outcome: Change in 24 hour mean systolic blood pressure measured by ABPM at 12 weeks after sacubitril/valsartan administration instead of ARB participants are using at enrollment.

Secondary Outcome

Safety assessments (increase in serum Cr >= 30%, incidence of hyperkalemia)
Change in 24 hour mean diastolic blood pressure measured by ABPM at 12 weeks.
Change in daytime mean systolic/diastolic blood pressure measured by ABPM at 12 weeks.
Change in nocturnal mean systolic/diastolic blood pressure measured by ABPM at 12 weeks.
Change in SD, and CV, of 24 hour, daytime, and nocturnal systolic/diastolic blood pressure measured by ABPM at 12 weeks.
Change in percentages of dipper, and non-dipper.
Change in mean moring home blood pressure, and home blood pressure variability (SD).
Change in office blood pressures.
Percentages of achievement of target office, or home, blood pressure levels.
Change in pulse rate, body weight, and body mass index.
Change in the following items.
Blood analysis
Hematology
Alb, AST, ALT, BUN, Cr, eGFR, UA, Na, K, Cl, Ca, P
NT-proBNP
PRA, PAC
LDL-cholesterol, HDL-cholesterol, triglyceride
Urine analysis
the natural logarithm of urine protein-to-creatinine ratio (UPCR)
urine NAG-to-creatinine ratio, urine beta 2 microglobulin
urine sodium-to-creatinine ratio

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

(i) Aged >= 18 years of age on day of signing informed consent (male/female)
(ii) CKD of G4-to-G5 categories (eGFR < 30 ml/min/1.73m2), not yet on dialysis
(iii) Current treatment with ARB (regardless of other antihypertensive drugs use, except for angiotensin converting enzyme (ACE) inhibitors and aliskiren)
(iv) Systolic office blood pressure >= 130 mmHg, or diastolic office blood pressure >= 80 mmHg
(Systolic office blood pressure >= 140 mmHg, or diastolic office blood pressure >= 90 mmHg, if participants are 75 years of age or older without proteinuria
(v) Written informed consent

Exclude criteria

(i) Bilateral renal artery stenosis, or renal artery stenosis in patients who have only one kidney.
(ii) Patients who were pregnant, or breastfeeding women.
(iii) Hyperkalemia (Serum potassium > 5.5 mEq/L)
(iv) History of angioedema
(v) Severe hepatic insufficiency and/or significant abnormal liver function (alanine aminotransferase or aspartate aminotransferase > 2 times the upper limit of the normal range, Child-Pugh category C)
(vi) Hypersensitivity for sacubitril/valsartan.
(vii) Current treatment with ACE inhibitors, or within 36 hours after ACE inhibitors discontinuance.
(viii) Current treatment with aliskiren.
(ix) Patients judged by the investigator to be ineligible for some other reason.
(x) office, or home, systolic blood pressure >= 200mmHg
(xi) Current treatment with maximum dose of ARBs
(xii) History of acute coronary syndrome, or stroke within the past 3 months.
(xiii) Patients under treatment with malignant tumor.
(xiv) New York Heart Association class II to IV heart failure.

Related Information

• Primary Sponsor: Kinguchi Sho