Chronic Kidney Disease(CKD), Nocturnal Hypertension
Conditions
Keywords
chronic kidney disease, isolated nocturnal hypertension
Brief summary
Hypertension guidelines recommend the application of ambulatory blood pressure monitoring in the diagnosis and treatment of patients with hypertension. Subtypes of hypertension such as nocturnal hypertension can be found through ambulatory blood pressure monitoring. Previous studies have reported that the prevalence of nocturnal hypertension, even isolated nocturnal hypertension, is higher in patients with chronic kidney disease, and it is associated with adverse events such as cardiovascular events and progression of renal dysfunction. However, the benefit of controlling nocturnal hypertension in patients with chronic kidney disease is unclear. In this study, a total of 200 patients with chronic kidney disease and isolated nocturnal hypertension will be enrolled. Patients will be randomly divided into two treatment groups: the active antihypertensive treatment group and the placebo treatment group (1:1). The antihypertensive treatment group will be treated with arotinolol or amlodipine and clonidine to control nocturnal blood pressure, while the control group will be treated with the corresponding placebos. Randomized patients will be followed up for 2 years to evaluate the effect of controlling isolated nocturnal hypertension on the progression of chronic kidney disease in terms of EPI-estimated glomerular filtration rate (eGFR) decline and change in proteinuria.
Interventions
DRUGAntihypertensive treatment with Arotinolol or Amlodipine or Clonidine
Participants will receive Almar 10 mg orally once daily between 8:00 PM and midnight. At the subsequent visit, if nocturnal blood pressure remains above the target of \<120/70 mmHg, Amlodipine Besylate will be added at a dose of 2.5 mg to 5 mg orally once daily. Should nocturnal blood pressure still not achieve the target at the following visit, Clonidine Hydrochloride 75 µg will be added to the regimen. The target for nocturnal blood pressure control is set at \<120/70 mmHg. For participants whose clinic blood pressure exceeds 140/90 mmHg, an unscheduled visit will be arranged within one month. If elevated clinic blood pressure persists during this visit, a 24-hour Ambulatory Blood Pressure Monitoring (ABPM) will be conducted. If the ABPM results indicate daytime blood pressure ≥135/85 mmHg, open-label add-on antihypertensive therapy will be initiated, prioritizing the use of antihypertensive medications outside of the study drugs to achieve blood pressure control.
DRUGPlacebo-controlled group
Participants are treated with corresponding placebo
Sponsors
Shanghai Institute of Hypertension
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must be 18 years of age or older. All genders are eligible; * Confirmed diagnosis of Chronic Kidney Disease (CKD) according to KDIGO. guidelines; * UACR \< 30 mg/g (3.4 mg/mmol) and eGFR between 20-44 mL/min/1.73 m²; or UACR between 30-300 mg/g (3.4-33.9 mg/mmol) and eGFR between 20-59 mL/min/1.73 m²; or UACR between 300-5000 mg/g (33.9-565 mg/mmol) and eGFR \> 20 mL/min/1.73 m² (CKD-EPI equation). * Office blood pressure measurements below 140/90 mmHg at both screening visits; * Daytime ambulatory blood pressure \< 135/85 mmHg and nighttime systolic blood pressure ≥ 120 mmHg or diastolic blood pressure ≥ 70 mmHg; * No use of corticosteroids, immunosuppressants, or biologic agents for at least one month prior to enrollment;
Exclusion criteria
* Presence of acute kidney injury or acute renal failure; * History of kidney transplantation; * Presence of severe arrhythmias, including severe atrial fibrillation, atrioventricular (AV) block, sinoatrial (SA) block, sinus bradycardia, malignant AV node reentrant tachycardia syndrome; * Secondary hypertension related to suspected or confirmed renal artery stenosis or adrenal gland disorders; * Poor glycemic control (HbA1c \> 12%); * Orthostatic hypotension (a decrease in blood pressure of \>20/10 mmHg within 3 minutes of standing from a sitting position); * Women who are pregnant or breastfeeding at the time of enrollment, or not employing contraception of reproductive age; * NYHA (New York Heart Association) Class III-IV congestive heart failure at the time of enrollment; * History of myocardial infarction, unstable angina, acute heart failure, stroke, transient ischemic attack (TIA), or cerebral hemorrhage within the 12 weeks prior to enrollment; * Underwent coronary revascularization (Percutaneous Coronary Intervention \[PCI\] or Coronary Artery Bypass Grafting \[CABG\]), or valve repair/replacement within the 12 weeks prior to enrollment, or planned to undergo any of the aforementioned surgical procedures after randomization; * Any other serious diseases outside the renal and cardiovascular domains, including but not limited to malignancies, with an expected survival of less than 2 years based on the investigator's clinical judgment; * Presence of active malignancy requiring pharmacological treatment; * AST (Aspartate Aminotransferase) or ALT (Alanine Aminotransferase) levels \>3 times the upper limit of normal (ULN); * Total bilirubin \>2 times ULN. Patients with Gilbert's syndrome who exhibit isolated bilirubin elevation do not need to be excluded;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in renal function from baseline after 2 year of treatment as assessed by EPI-estimated glomerular filtration rate (eGFR) | 2 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in urine protein from baseline after 1 and 2 years of treatment as assessed by urinary albumin-to-creatinine ratio(UACR) | 1 and 2 years | — |
| 50% decrease of albumin-to-creatinine ratio (UACR) from baseline after 1 and 2 years of treatment | 1 and 2 years | — |
| Incidence of kidney composite endpoint including end-stage renal disease (ESRD), kidney replacement therapy, or sustained EPI-estimated glomerular filtration rate (eGFR) decline ≥ 40%. | 1 and 2 years | — |
| Incidence of sustained EPI-estimated glomerular filtration rate (eGFR) < 15 ml/min/1.73 m² | 1 and 2 years | — |
| Incidence of cardiovascular endpoints including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or heart failure hospitalization | 1 and 2 years | — |
| Change in renal function from baseline after 1 year of treatment as assessed by EPI-estimated glomerular filtration rate (eGFR) | 1 year | — |
| Changes in pulse wave velocity (PWV) after 1 and 2 years of treatment from baseline | 1 and 2 years | — |
| Incidence of mortality including all-cause, cardiovascular-related, and renal-related. | 1 and 2 years | — |
| Changes in office and ambulatory blood pressure levels after 1 and 2 years of treatment from baseline | 1 and 2 years | — |
| Hypotension-related adverse events | 1 and 2 years | dizziness, falls, office blood pressure below 90/60 mmHg, orthostatic hypotension (blood pressure drop exceeding 20/10 mmHg within 3 minutes of standing compared to sitting), and acute kidney injury \[serum creatinine increase ≥0.3 mg/dl (≥26.5 μmol/L) within 48 hours; or serum creatinine rising to ≥1.5 times baseline value within 7 days; or urine output \<0.5 mL/(kg·h) for ≥ 6 hours\]. |
| Changes in cardiac injury after 1 and 2 years of treatment from baseline as assessed by left ventricular mass index or E/E' or cardiac troponin | 1 and 2 years | — |
Contacts
Primary ContactYan Li
Outcome results
None listed