Protecting Renal Function in Chronic Kidney Disease Patients with Isolated Nighttime Hypertension

Official title

Protection of Renal Function by Antihypertensive Treatment in Patients with Chronic Kidney Disease and Isolated Nighttime Hypertension

Overview

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

• Drug Antihypertensive 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 wh
• Drug Placebo-controlled group
  Participants are treated with corresponding placebo

Primary outcome measures

• Change in renal function from baseline after 2 year of treatment as assessed by EPI-estimated glomerular filtration rate (eGFR) [Time frame: 2 years]

Secondary outcome measures (11)

• Change in renal function from baseline after 1 year of treatment as assessed by EPI-estimated glomerular filtration rate (eGFR) [Time frame: 1 year]
• Change in urine protein from baseline after 1 and 2 years of treatment as assessed by urinary albumin-to-creatinine ratio(UACR) [Time frame: 1 and 2 years]
• 50% decrease of albumin-to-creatinine ratio (UACR) from baseline after 1 and 2 years of treatment [Time frame: 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%. [Time frame: 1 and 2 years]
• Incidence of sustained EPI-estimated glomerular filtration rate (eGFR) < 15 ml/min/1.73 m² [Time frame: 1 and 2 years]
• Incidence of cardiovascular endpoints including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or heart failure hospitalization [Time frame: 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 [Time frame: 1 and 2 years]
• Changes in pulse wave velocity (PWV) after 1 and 2 years of treatment from baseline [Time frame: 1 and 2 years]
• Incidence of mortality including all-cause, cardiovascular-related, and renal-related. [Time frame: 1 and 2 years]
• Changes in office and ambulatory blood pressure levels after 1 and 2 years of treatment from baseline [Time frame: 1 and 2 years]
• Hypotension-related adverse events [Time frame: 1 and 2 years]

Eligibility criteria

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;

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• 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. PMID 23732715
• 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. PMID 23499048
• 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 PMID 30165516
• 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. PMID 8957032
• 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. PMID 19193736
• 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. PMID 27383068

Identifiers

NCT: NCT06780865 · PRECISE Trial

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗