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

Hypertension Clinical Trial

— CENTRAL-CKD  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05163158
• Other study ID #: CENTRAL-CKD Protocol Version 1
• Status: Recruiting
• Phase: N/A
• Start date: May 24, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: August 2023
• Source: Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal
• Contact: Guylaine Marcotte
• Phone: 1(514)338-2222
• Email: guylaine.marcotte[@]cnmtl.gouv.qc.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 116
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Kidney Diseases
• Hypertension
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Other:
• Central vs brachial systolic blood pressure targeting
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.

Locations

Country	Name	City	State
Canada	Hôpital du Sacré-Coeur de Montréal	Montréal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Progression towards kidney failure (sustained eGFR loss = 40%, kidney replacement therapy initiation or death from renal failure)		12 months
Other	Major adverse cardiovascular adverse events (cardiovascular mortality, myocardial infarction, stroke, heart failure requiring hospitalisation, peripheral artery disease requiring revascularisation or amputation)	Composite and individuals outcomes	12 months
Other	All-cause hospitalisation		12 months
Other	All-cause mortality		12 months
Other	Acute kidney injury (>50% increase in serum creatinine)		12 months
Other	Symptomatic orthostatic hypotension, dizziness, light headedness, injurious falls, syncope or any unexpected event attributable to the intervention		12 months
Primary	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
Primary	Feasibility: Recruitment rate	Proportion of randomized participants relative to the number of screened participants.; Feasibility criteria (No / Probable / Yes): <40% / 40-80% / >80%	Baseline
Primary	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
Primary	Feasibility: Completion rate	Proportion of randomized participants who complete the trial Feasibility criteria (No / Probable / Yes): <40% / 40-80% / >80%	12 months
Primary	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
Primary	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
Primary	Feasibility: Therapeutic inertia rate	Proportion of therapeutic inertia Feasibility criteria (No / Probable / Yes): >60% / 60-30% / <30%	12 months
Primary	Difference in aortic stiffness	Carotid-femoral pulse wave velocity	12 months
Secondary	Difference in eGFR decline		12 months
Secondary	Change in albuminuria		12 months
Secondary	Difference in Daily Defined Doses of blood pressure drugs		12 months
Secondary	Quality of life (KDQOL-SF questionnaire)	Score 0 to 100. Higher score represents better quality of life	12 months