Clinical trial NCT05163158: CENtral Blood Pressure Targeting: a Pragmatic RAndomized Pilot TriaL in Advanced Chronic Kidney Disease
Official title: CENtral Blood Pressure Targeting: a Pragmatic RAndomized Pilot TriaL in Advanced Chronic Kidney Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Chronic Kidney Diseases
Hypertension
Keywords: Central blood pressure
Central hypertension
Chronic kidney disease
Hypertension
Arterial stiffness
Lead sponsor: Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal
Sponsor class: OTHER
First posted: 2021-12-20
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Over 18 years of age;
2. eGFR \<30 mL/min/1.73m2 as determined by the CKD-EPI equation (within 30 days of screening);
3. Office brachial cuff systolic blood pressure between 120 and 160 mmHg (using automated office blood pressure).

Exclusion Criteria:

1. Already taking 5 or more anti-hypertensive medications (any class)
2. Unwillingness to change anti-hypertensive medication by the attending Nephrologist or patient
3. Recent acute kidney injury (\>50% increase in serum creatinine in preceding 30 days)
4. Previous kidney replacement therapy (kidney transplant, hemodialysis or peritoneal dialysis)
5. Recent myocardial infarction, stroke, heart failure (in preceding 30 days)
6. Recent injurious fall requiring hospitalisation (in preceding 30 days)
7. Concomitant major illness / comorbidity that may result in death in the next 6 months
8. Participation in another study that is likely to affect BP levels
9. Inability to provide consent due to cognitive impairment.

Primary outcomes:
measure: Feasibility: Consent rate
timeFrame: Baseline
measure: Feasibility: Recruitment rate
timeFrame: Baseline
measure: Feasibility: Achieved BP target rate
timeFrame: 12 months
measure: Feasibility: Completion rate
timeFrame: 12 months
measure: Feasibility: Recruitment pace
timeFrame: 12 months after activation of last site
measure: Feasibility: Divergent treatment decision rate
timeFrame: 12 months
measure: Feasibility: Therapeutic inertia rate
timeFrame: 12 months
measure: Difference in aortic stiffness
timeFrame: 12 months
Secondary outcomes:
measure: Difference in eGFR decline
timeFrame: 12 months
measure: Change in albuminuria
timeFrame: 12 months
measure: Difference in Daily Defined Doses of blood pressure drugs
timeFrame: 12 months
measure: Quality of life (KDQOL-SF questionnaire)
timeFrame: 12 months
Other outcomes:
measure: Progression towards kidney failure (sustained eGFR loss ≥ 40%, kidney replacement therapy initiation or death from renal failure)
timeFrame: 12 months
measure: Major adverse cardiovascular adverse events (cardiovascular mortality, myocardial infarction, stroke, heart failure requiring hospitalisation, peripheral artery disease requiring revascularisation or amputation)
timeFrame: 12 months
measure: All-cause hospitalisation
timeFrame: 12 months
measure: All-cause mortality
timeFrame: 12 months
measure: Acute kidney injury (>50% increase in serum creatinine)
timeFrame: 12 months
measure: Symptomatic orthostatic hypotension, dizziness, light headedness, injurious falls, syncope or any unexpected event attributable to the intervention
timeFrame: 12 months
Locations:
city: Montréal
country: Canada
facility: Hôpital du Sacré-Coeur de Montréal
state: Quebec
Study officials:
affiliation: Hôpital Sacré-Coeur de Montréal
name: Remi Goupil, MD MSc
role: PRINCIPAL_INVESTIGATOR
References: