Fractional Flow Reserve to Determine Atherosclerosis Renal Hypertension Stenting

Study Overview
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Brief Summary
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Although randomized trials have demonstrated there is no benefit of renal-artery stenting in addition to medical therapy for patients with atherosclerosis renal artery stenosis, many patients indeed gained benefit in daily practices after stenting, such as reduction in blood pressure and recovery in renal functions. One important gap is that there is no universal standard to determine whether to stent in these patients. Fraction Flow Reserve (FFR) has been studied for many year in chronic coronary heart disease and FFR-guided revascularization strategy is known to be better than both angiography-guided revascularization and medication alone. The goal of this clinical trial is to learn whether Fraction Flow Reserve (FFR) is appropriate to determine stenting in hypertension patients with atherosclerosis renal artery stenosis. The main questions it aims to answer are: Is it appropriate to use FFR to determine whether or not stenting for hypertension patients with atherosclerosis renal artery stenosis? To provide detailed data supporting design of further trial, such as sample size calculating, cut-off value for FFR in renal artery stenosis, etc. Participants met the inclusive/exclusive criteria will be randomized to stenting or not in the renal artery, then hyperemic FFR induced by dopamine will be measured in all participants. If FFR is ≥0.80, randomization will be applied. If FFR is <0.80, randomization will be ignored, and stenting will be performed as planned. The blood pressure and anti-hypertensive medications will be compared before and 3 months after the procedure based on ambulatory blood pressure monitoring, all participants will be followed up for 1 year.

Official Title
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Fractional Flow Reserve to Determine the ApproprIateness of Percutaneous Renal Artery Intervention in Atherosclerosis Renal Hypertension Patients: a Pilot Randomized Trial

Conditions
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Renal Artery Stenosis Atherosclerotic, Secondary Hypertension Renal Arterial

Intervention / Treatment
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* Drug: Dopamine
* Diagnostic Test: Fractional Flow Reserve, Renal
* Device: Renal artery stenting


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: With recorded hypertension, AND the blood pressure is not controlled (SBP ≥140mmHg and/or DBP ≥90mmHg) on 2 or more classes of anti-hypertensive drugs; Evidence of renal artery stenosis and undergoing renal artery angiography; Able to follow the study protocol and provide informed consent; Renal artery angiography shows at least 1 main artery with stenosis of 50%-90%, AND the diameter is ≥ 4.0mm. Exclusion Criteria: SBP ≥200mmHg and/or DBP ≥120mmHg at the day or randomization; Fibromuscular dysplasia or other non-atherosclerotic renal artery stenosis; Pregnancy or unknow pregnancy status in female of childbearing potential; Participation in any drug or device trial during the study period; Any stroke/TIA, OR with ≥70% stenosis of carotid artery; Any major surgery, myocardial infarction or interventional therapy 30 days prior to study entry; LVEF <30%; Comorbid condition causing life expectancy ≤1 year; Allergy to contrast or any of the following: aspirin, clopidogrel; Previous kidney transplant; Previous renal artery bypass surgery or stent intervention; Kidney size less than 8 cm measured by ultrasound; Local lab serum Cr >3.0 mg/dl (265.2μmol/l) on the day of randomization; Reference vessel size <4 mm or >8 mm.

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: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Not stenting<br>Hyperemic FFR induced by 50μg/kg of dopamine via renal artery will be measured. If FFR is ≥0.80, randomization will be applied, and no stenting will be implanted. If FFR is <0.80, randomization will be ignored, and stenting will be performed. | Drug: Dopamine<br>* A bolus dose of 50μg/kg dopamine via renal artery to induce hyperemic status<br>Diagnostic Test: Fractional Flow Reserve, Renal<br>* Renal FFR will be measured based on SOP<br>Device: Renal artery stenting<br>* Renal artery stenting will be implanted based on the protocol<br>|
| Other: Stenting<br>Hyperemic FFR induced by 50μg/kg of dopamine via renal artery will be measured. No matter FFR is, stenting will be performed as planned. | Drug: Dopamine<br>* A bolus dose of 50μg/kg dopamine via renal artery to induce hyperemic status<br>Diagnostic Test: Fractional Flow Reserve, Renal<br>* Renal FFR will be measured based on SOP<br>Device: Renal artery stenting<br>* Renal artery stenting will be implanted based on the protocol<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in daytime mean systolic blood pressure as measured by 24-hour Ambulatory Blood Pressure Monitoring (ABPM) |  | From baseline to 3 months post-procedure | 
| Change in the composite index of antihypertensive drugs | Change in the composite index of antihypertensive drugs. Drug Composite Index = Weight (number of classes of antihypertensive drugs) × (sum of doses) | From baseline to 3 months post-procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in systolic blood pressure as measured by 24-hour ABPM |  | From baseline to 3 months post-procedure | 
| Change in diastolic blood pressure as measured by 24-hour ABPM |  | From baseline to 3 months post-procedure | 
| Change in home blood pressure |  | From baseline to 3 months post-procedure | 
| Change in office blood pressure |  | From baseline to 3 months post-procedure | 
| Change in the composite index of antihypertensive drugs to reach target blood pressure | Change in the composite index of antihypertensive drugs to reach target blood pressure. Drug Composite Index = Weight (number of classes of antihypertensive drugs) × (sum of doses) | From baseline to 1 year post-procedure | 
| Change in ABPM |  | From baseline to 6 months, 1 year post-procedure | 
| All-cause death |  | From baseline to 1 year post-procedure | 
| Cardiac death |  | From baseline to 1 year post-procedure | 
| Acute myocardial infarction incidence | Based on universal definition of acute myocardial infarction | From baseline to 1 year post-procedure | 
| Non-fatal stroke incidence | Based on medical records under outcome committee's judge | From baseline to 1 year post-procedure | 
| Rehospitalization due to heart failure incidence | Based on medical records under outcome committee's judge | From baseline to 1 year post-procedure | 
| Increase in serum creatinine or dialysis |  | From baseline to 1 year post-procedure |