UMIN-CTR Clinical Trial
| Unique ID issued by UMIN | UMIN000057389 |
|---|---|
| Receipt number | R000065558 |
| Scientific Title | The Effect of Sacubitril/Valsartan on Kidney Function in Hypertensive Patients with Chronic Kidney Disease: A Randomized Controlled Trial |
| Date of disclosure of the study information | 2025/04/01 |
| Last modified on | 2025/03/24 22:31:50 |
* This page includes information on clinical trials registered in UMIN clinical trial registed system.
* We don't aim to advertise certain products or treatments
Basic information
Public title
The Effect of Sacubitril/Valsartan on Kidney Function in Hypertensive Patients with Chronic Kidney Disease: A Randomized Controlled Trial
Acronym
The Effect of Sacubitril/Valsartan in Hypertensive Patients with CKD
Scientific Title
The Effect of Sacubitril/Valsartan on Kidney Function in Hypertensive Patients with Chronic Kidney Disease: A Randomized Controlled Trial
Scientific Title:Acronym
The Effect of Sacubitril/Valsartan in Hypertensive Patients with CKD
Region
| Japan |
Condition
Condition
Patients with chronic kidney disease (CKD) whose blood pressure is not under control
Classification by specialty
| Medicine in general | Nephrology |
Classification by malignancy
Others
Genomic information
NO
Objectives
Narrative objectives1
To determine whether the angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan has a renoprotective effect compared with the combination of a thiazide diuretic (TZD) and an angiotensin II receptor blocker (ARB) in CKD patients with hypertension.
Basic objectives2
Efficacy
Basic objectives -Others
Trial characteristics_1
Confirmatory
Trial characteristics_2
Explanatory
Developmental phase
Phase IV
Assessment
Primary outcomes
The primary endpoint is the rate of decline in kidney function. Estimated glomerular filtration rate (eGFR) slope during the 12-month treatment period is calculated by linear regression from eGFR (both from serum creatinine and from serum cystatin C) measured every 1 to 3 months. The eGFR slope for the 12-month treatment period is calculated by linear regression.
We will also compare the trend of eGFR in the two groups using a linear mixed model or a generalized linear mixed model with fixed effects of time period and various confounding factors.
Key secondary outcomes
Antihypertensive effects [office and home (systolic and diastolic) blood pressure at the end of the 12-month treatment period.of the 12-month treatment period between the two groups, as well as the degree of blood pressure reduction from baseline and blood pressure trends using a linear mixed model (as with eGFR)].
Body weight and body mass index (will be compared in the same way as blood pressure)
N-terminal fragment of brain natriuretic peptide precursor (NT-proBNP) (at the end of the 12-month treatment period will be compared between the two groups, as well as the degree of NT-proBNP change compared to baseline)
In addition to urine protein and urine albumin, liver-type fatty acid binding protein (L-FABP) and markers of tubular damage such as beta2-microglobulin and N-acetylglucosaminidase (NAG) (mainly at the end of the 12-month treatment period)
Urinary electrolytes such as sodium, potassium, chloride, creatinine and urea nitrogen Serum sodium, potassium, chloride, uric acid, triglycerides and other parameters related to lipid and glucose metabolism
Base
Study type
Interventional
Study design
Basic design
Parallel
Randomization
Randomized
Randomization unit
Individual
Blinding
Open -no one is blinded
Control
Active
Stratification
YES
Dynamic allocation
YES
Institution consideration
Institution is considered as adjustment factor in dynamic allocation.
Blocking
NO
Concealment
Central registration
Intervention
No. of arms
2
Purpose of intervention
Treatment
Type of intervention
| Medicine |
Interventions/Control_1
Intervention group (ARNI group):
First, there will be an observation period (1-3 months) during which patients will switch from their original angiotensin II receptor blocker (ARB) to 20-40 mg olmesartan.
In the subsequent treatment period (12 months), olmesartan 20 mg and 40 mg are switched to sacubitril/valsartan 200 mg and 400 mg, respectively.
Dose adjustment of antihypertensive medications will be made by the attending physician as appropriate, but the ARNI group will not use TZDs and the TZD/ARB group will not use ARNIs.
Interventions/Control_2
Control group (TZD/ARB group):
First, there will be an observation period (1-3 months) during which patients will switch from their original angiotensin II receptor blocker (ARB) to 20-40 mg olmesartan.
In the subsequent treatment phase, trichlormethiazide, a thiazide diuretic, is added and adjusted in the range of 1-8 mg.
Dose adjustment of antihypertensive medications will be made by the attending physician as appropriate, but the ARNI group will not use TZDs and the TZD/ARB group will not use ARNIs.
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10
Eligibility
Age-lower limit
| 18 | years-old | <= |
Age-upper limit
| Not applicable |
Gender
Male and Female
Key inclusion criteria
The following conditions must be met by outpatients attending the Department of Nephrology, International University of Health and Welfare Narita Hospital, Department of Nephrology, International University of Health and Welfare Hospital, Department of Nephrology and Hypertension, Kameda General Hospital, Department of Internal Medicine, Tokyo Dental University Ichikawa General Hospital, Department of Nephrology, Endocrinology and Diabetes, Tokyo Bay Urayasu Ichikawa Medical Center, and Department of Nephrology, Gyotoku General Hospital.
Patients whose eGFR is 15-60 mL/min/1.73m2 (CKD G3a-4) based on blood sampling within 3 months.
Patients on RAS inhibitors but with poor blood pressure control according to the antihypertensive targets of "The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019)". Specifically, for patients aged 75 years or older, patients with bilateral carotid stenosis or main cerebral artery occlusion, and patients without proteinuria (<0.15 g/gCr), the office blood pressure and home blood pressure should be 140/90 mmHg and 135/85 mmHg or higher, respectively; for other patients, the office blood pressure and home blood pressure should be 130/80 mmHg and 125/75 mmHg or higher, respectively.
Patients who have not taken ARNI or TZD for 3 months.
Patients who have been fully informed about the study and who have given written consent of their own free will.
Key exclusion criteria
In consideration of the impact on safety evaluation, the following exclusion criteria are used
Patients with marked hypertension (systolic blood pressure >180 or diastolic blood pressure >110 mmHg sustained).
Patients with symptomatic coronary artery disease or cerebrovascular disease within 3 months.
Patients with uncontrolled heart failure (NYHA III or higher).
Patients with arrhythmia with severe symptoms or fatal arrhythmia.
Patients with acute kidney injury.
Patients with nephrotic syndrome.
Patients with terminal cancer who are expected to live less than one year.
Other patients who are deemed inappropriate as research subjects by the principal investigator.
Target sample size
120
Research contact person
Name of lead principal investigator
| 1st name | Kiyotaka |
| Middle name | |
| Last name | Uchiyama |
Organization
International University of Health and Welfare Narita Hospital
Division name
Department of Nephrology
Zip code
286-8520
Address
852 Hatakeda, Narita, Chiba, Japan
TEL
+81-476-35-5600
kiyo.0817.piyo@iuhw.ac.jp
Public contact
Name of contact person
| 1st name | Kiyotaka |
| Middle name | |
| Last name | Uchiyama |
Organization
International University of Health and Welfare Narita Hospital
Division name
Department of Nephrology
Zip code
286-8520
Address
852 Hatakeda, Narita, Chiba, Japan
TEL
+81-476-35-5600
Homepage URL
kiyo.0817.piyo@iuhw.ac.jp
Sponsor or person
Institute
International University of Health and Welfare Narita Hospital
Institute
Department
Personal name
Kiyotaka Uchiyama
Funding Source
Organization
International University of Health and Welfare
Organization
Division
Category of Funding Organization
Other
Nationality of Funding Organization
Other related organizations
Co-sponsor
Department of Nephrology, International University of Health and Welfare, Department of Nephrology and Hypertension, Kameda General Hospital, Department of Internal Medicine, Tokyo Dental University Ichikawa General Hospital, Department of Nephrology, Endocrinology and Diabetes, Tokyo Bay Urayasu Ichikawa Medical Center, and Department of Nephrology, Gyotoku General Hospital.
Name of secondary funder(s)
IRB Contact (For public release)
Organization
Ethics Review Board for Clinical Research of International University of Health and Welfare
Address
852 Hatakeda, Narita, Chiba, Japan
Tel
+81-476-35-5613
rinri_md@iuhw.ac.jp
Secondary IDs
Secondary IDs
NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW
Institutions
Institutions
国際医療福祉大学成田病院（千葉県）、国際医療福祉大学病院（栃木県）、亀田総合病院（千葉県）、東京歯科大学市川総合病院（千葉県）、東京ベイ・浦安市川医療センター（千葉県）、行徳総合病院（千葉県）
Other administrative information
Date of disclosure of the study information
| 2025 | Year | 04 | Month | 01 | Day |
Related information
URL releasing protocol
Publication of results
Unpublished
Result
URL related to results and publications
Number of participants that the trial has enrolled
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description
Progress
Recruitment status
Preinitiation
Date of protocol fixation
| 2025 | Year | 03 | Month | 12 | Day |
Date of IRB
| 2025 | Year | 03 | Month | 12 | Day |
Anticipated trial start date
| 2025 | Year | 04 | Month | 01 | Day |
Last follow-up date
| 2029 | Year | 03 | Month | 31 | Day |
Date of closure to data entry
Date trial data considered complete
Date analysis concluded
Other
Other related information
Management information
Registered date
| 2025 | Year | 03 | Month | 24 | Day |
Last modified on
| 2025 | Year | 03 | Month | 24 | Day |
Link to view the page
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000065558
