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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Anti-hypertensive treatment group | Experimental | The patients will be treated with Arotinolol and/or Amlodipine and/or Clonidine. |
|
| Control group | Placebo Comparator | Placebo was used in the control group. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Antihypertensive treatment with Arotinolol or Amlodipine or Clonidine | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in renal function from baseline after 2 year of treatment as assessed by EPI-estimated glomerular filtration rate (eGFR) | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Change in renal function from baseline after 1 year of treatment as assessed by EPI-estimated glomerular filtration rate (eGFR) | 1 year | |
| Change in urine protein from baseline after 1 and 2 years of treatment as assessed by urinary albumin-to-creatinine ratio(UACR) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yan Li | Contact | +86 13482234463 | ly11238@rjh.com.cn |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23732715 | Background | Stevens PE, Levin A; Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group Members. Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med. 2013 Jun 4;158(11):825-30. doi: 10.7326/0003-4819-158-11-201306040-00007. | |
| 23499048 |
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| Placebo-controlled group | Drug | Participants are treated with corresponding placebo |
|
| 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 |
| 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 |
| 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 | 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]. | 1 and 2 years |
| Palevsky PM, Liu KD, Brophy PD, Chawla LS, Parikh CR, Thakar CV, Tolwani AJ, Waikar SS, Weisbord SD. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury. Am J Kidney Dis. 2013 May;61(5):649-72. doi: 10.1053/j.ajkd.2013.02.349. Epub 2013 Mar 15. |
| 30165516 | Background | Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, Clement DL, Coca A, de Simone G, Dominiczak A, Kahan T, Mahfoud F, Redon J, Ruilope L, Zanchetti A, Kerins M, Kjeldsen SE, Kreutz R, Laurent S, Lip GYH, McManus R, Narkiewicz K, Ruschitzka F, Schmieder RE, Shlyakhto E, Tsioufis C, Aboyans V, Desormais I; ESC Scientific Document Group. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018 Sep 1;39(33):3021-3104. doi: 10.1093/eurheartj/ehy339. No abstract available. |
| 8957032 | Background | Buckalew VM Jr, Berg RL, Wang SR, Porush JG, Rauch S, Schulman G. Prevalence of hypertension in 1,795 subjects with chronic renal disease: the modification of diet in renal disease study baseline cohort. Modification of Diet in Renal Disease Study Group. Am J Kidney Dis. 1996 Dec;28(6):811-21. doi: 10.1016/s0272-6386(96)90380-7. |
| 19193736 | Background | Chen N, Wang W, Huang Y, Shen P, Pei D, Yu H, Shi H, Zhang Q, Xu J, Lv Y, Fan Q. Community-based study on CKD subjects and the associated risk factors. Nephrol Dial Transplant. 2009 Jul;24(7):2117-23. doi: 10.1093/ndt/gfn767. Epub 2009 Feb 4. |
| 27383068 | Background | Hill NR, Fatoba ST, Oke JL, Hirst JA, O'Callaghan CA, Lasserson DS, Hobbs FD. Global Prevalence of Chronic Kidney Disease - A Systematic Review and Meta-Analysis. PLoS One. 2016 Jul 6;11(7):e0158765. doi: 10.1371/journal.pone.0158765. eCollection 2016. |
| ID | Term |
|---|---|
| D051436 | Renal Insufficiency, Chronic |
| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C024523 | arotinolol |
| D017311 | Amlodipine |
| D003000 | Clonidine |
| ID | Term |
|---|---|
| D004095 | Dihydropyridines |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D048288 | Imidazolines |
| D007093 | Imidazoles |
| D001393 | Azoles |
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