CENtral Blood Pressure Targeting: A Pragmatic RAndomized Pilot triaL in Advanced Chronic Kidney Disease

Study Overview
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Brief Summary
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Background: Emerging data favors aortic blood pressure (BP) over brachial cuff BP in predicting CV and renal complications, as this BP directly impacts the heart, brain and kidneys. In parallel, central BP measuring devices have been developed that are more accurate towards aortic BP and easy to use without training. In no other condition than advanced chronic kidney disease (CKD) is BP control as important, since undertreatment is associated with adverse CV events and progression towards end-stage kidney disease (ESKD), while overtreatment similarly leads to adverse CV events and injurious falls but also acute kidney injury which can precipitate ESKD. To this day, standard BP management relies on brachial cuff BP, which is an imprecise surrogate marker of aortic BP, more so in the advanced CKD population. Considering that these patients have a high risk of CV morbidity and mortality and is a group where brachial BP may be the least reliable, it can be beneficial to manage hypertension in this population using central BP measurements. With the development of affordable and easy to use central BP devices, routine use of central BP in hypertension would now become a reality. However, the superiority of central BP to traditional brachial cuff BP in regard to clinical outcomes will first need to be demonstrated. Objectives: To demonstrate that targeting central BP in advanced CKD patients as opposed to brachial cuff BP is feasible and results in lower arterial stiffness after 12 months of follow-up. Methods: The CENTRAL-CKD trial is an investigator-initiated prospective parallel-group 1:1 randomized double-blinded multicenter pragmatic pilot trial. Patients with CKD stages 4 and 5 (n=116) will be randomized to either a central systolic BP target < 130 mmHg (intervention) or brachial systolic BP target < 130 mmHg (standard care). Central and brachial BP will be concomitantly measured, with treating physicians, patients and investigators blinded towards allocation. As this trial is of a pragmatic design, all other aspects of BP and CKD management, including anti-hypertensive treatment-related decisions, diastolic BP targets, and clinical and laboratory follow-ups will be at the discretion of the attending Nephrologist. The primary outcomes include feasibility of large-scale trial using prespecified criteria and aortic stiffness (carotid-femoral pulse wave velocity) at 12 months. Other cardiovascular, renal, quality of life and safety outcomes will be evaluated. Importance: CENTRAL-CKD is designed as a pilot trial aimed at providing the framework and justification to proceed to a large-scale trial with adequate power to detect the impact of the proposed intervention on clinically important outcomes.

Official Title
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CENtral Blood Pressure Targeting: A Pragmatic RAndomized Pilot triaL in Advanced Chronic Kidney Disease

Conditions
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Chronic Kidney Diseases, Hypertension

Intervention / Treatment
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* Other: Central vs brachial systolic blood pressure targeting


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Over 18 years of age; eGFR <30 mL/min/1.73m2 as determined by the CKD-EPI equation (within 30 days of screening); Office brachial cuff systolic blood pressure between 120 and 160 mmHg (using automated office blood pressure). Exclusion Criteria: Already taking 5 or more anti-hypertensive medications (any class) Unwillingness to change anti-hypertensive medication by the attending Nephrologist or patient Recent acute kidney injury (>50% increase in serum creatinine in preceding 30 days) Previous kidney replacement therapy (kidney transplant, hemodialysis or peritoneal dialysis) Recent myocardial infarction, stroke, heart failure (in preceding 30 days) Recent injurious fall requiring hospitalisation (in preceding 30 days) Concomitant major illness / comorbidity that may result in death in the next 6 months Participation in another study that is likely to affect BP levels Inability to provide consent due to cognitive impairment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Central BP target<br>Participants randomized to central BP target will be treated with anti-hypertensive agents to achieve a clinic central SBP < 130 mmHg. | Other: Central vs brachial systolic blood pressure targeting<br>* Participants will be randomized to either a central BP target (intervention) or a brachial BP target (standard care). For each group, the source of the BP (central or brachial) will be blinded and only the BP values will be provided to the attending Nephrologist. In both cases, the target SBP will be <130 mmHg.<br>|
| Active Comparator: Brachial BP target (standard of care)<br>Participants randomized to a brachial BP target will be treated with anti-hypertensive drugs to achieve a clinic brachial SBP <130 mmHg. | Other: Central vs brachial systolic blood pressure targeting<br>* Participants will be randomized to either a central BP target (intervention) or a brachial BP target (standard care). For each group, the source of the BP (central or brachial) will be blinded and only the BP values will be provided to the attending Nephrologist. In both cases, the target SBP will be <130 mmHg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility: Consent rate | Proportion of participants who provide consent relative to the number approached for participation. Feasibility criteria (No / Probable / Yes): <30% / 30-60% / >60% | Baseline | 
| Feasibility: Recruitment rate | Proportion of randomized participants relative to the number of screened participants. Feasibility criteria (No / Probable / Yes): <40% / 40-80% / >80% | Baseline | 
| Feasibility: Achieved BP target rate | Proportion of randomized participants who achieve BP target at 12 months Feasibility criteria (No / Probable / Yes): <30% / 30-60% / >60% | 12 months | 
| Feasibility: Completion rate | Proportion of randomized participants who complete the trial Feasibility criteria (No / Probable / Yes): <40% / 40-80% / >80% | 12 months | 
| Feasibility: Recruitment pace | Number of participants recruited after 24 months of activation for all sites Feasibility criteria (No / Probable / Yes): <54 / 54-81 / >81 | 12 months after activation of last site | 
| Feasibility: Divergent treatment decision rate | Proportion of divergent treatment decision based on central BP compared to brachial BP Feasibility criteria (No / Probable / Yes): <10% / 10-30% / >30% | 12 months | 
| Feasibility: Therapeutic inertia rate | Proportion of therapeutic inertia Feasibility criteria (No / Probable / Yes): >60% / 60-30% / <30% | 12 months | 
| Difference in aortic stiffness | Carotid-femoral pulse wave velocity | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in eGFR decline |  | 12 months | 
| Change in albuminuria |  | 12 months | 
| Difference in Daily Defined Doses of blood pressure drugs |  | 12 months | 
| Quality of life (KDQOL-SF questionnaire) | Score 0 to 100. Higher score represents better quality of life | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Central blood pressure, Central hypertension, Chronic kidney disease, Hypertension, Arterial stiffness