Effectiveness and Safety of BiSAAE for Resistant Hypertension.

Effectiveness and Safety of Bilateral Superselective Adrenal Arterial Embolization (BiSAAE) for Resistant Hypertension

Hypertension is a common problem, affecting >1.1 billion people worldwide. Unfortunately, fewer than one in five treated patients with hypertension have their blood pressure (BP) under control. The increasing number of people with uncontrolled BP despite the use of three or more antihypertensive agents at optimal or maximally tolerated doses, with one of those agents preferably being a diuretic has been described as the resistant hypertension (RH). Achieving BP control is essential because patients with hypertension who have uncontrolled BP have significantly higher rates of all-cause, cardiovascular, heart disease and cerebrovascular disease mortality compared to normotensive individuals, whereas mortality risk in patients with well-controlled BP does not differ from that in normotensive individuals. There are a number of potential factors that contribute to the suboptimal control of hypertension, including medication non-adherence and prescribing inertia. This highlights the limitations of purely pharmacological approaches for the effective management of hypertension. In fact, the activation of the renin-angiotensin-aldosterone system (RAAS) and sympatho-adrenomedullary system play a pathogenic role in triggering and sustaining RH. Superselective adrenal arterial embolization (SAAE) is a catheter-based percutaneous transluminal procedure which selectively injects ethanol into adrenal artery to ablate part of the adrenal gland for suppression of excessive aldosterone and catecholamines. Over the last decade, unilateral SAAE has emerged as a potential treatment option for patients with primary aldosteronism. Whether this approach can be extrapolated to patients with RH is unclear. We thus set out to perform a randomized trial to compare the safety and efficacy of bilateral SAAE with antihypertensive medications in treating RH.

Study Overview

• Status: Not yet recruiting
• Conditions: Resistant Hypertension
• Intervention / Treatment: Procedure: BiSAAE; Procedure: traditional triple antihypertensive treatment

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yaqiong Zhou; Phone Number: +8615184399329; Email: 1273868593@qq.com
• Study Contact Backup: Name: Peijian Wang; Phone Number: +861880718263; Email: wpjmed@aliyun.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female, aged between 30-65 years old.
• Patients with resist hypertension (office systolic blood pressure ≥140 mmHg, and/or office diastolic blood pressure ≥90 mmHg, and/or 24-h average systolic blood pressure ≥130 mmHg) with rational lifestyle change and triple antihypertensive drugs (irbesartanhydrochlorothiazide 162.5 mg/d, amlodipine 5 mg/d) for at least 4 weeks.
• Informed consent signed and agreed to participate in this trial.

Exclusion Criteria:

• Secondary hypertension
• Adrenergic insufficiency.
• adrenocortical insufficiency
• Renal failure eGFR<60 mL/min/1.73 m2
• Heart failure with NYHA grade Ⅱ-Ⅳ grade or unstable angina, severe cardiovascular and cerebrovascular stenosis, myocardial infarction, intracranial aneurysm, stroke and other acute cardiovascular events.
• Acute infections, tumors and severe arrhythmias, psychiatric disorders, drugs or alcohol addicts.
• Liver dysfunction or the following history of liver disease: AST or ALT 3 times higher than the upper limit, liver cirrhosis, history of hepatic encephalopathy, esophageal variceal history or portal shunt history.
• Fertile woman without contraceptives.
• Coagulation dysfunction.
• Pregnant women or lactating women.
• Participated in other clinical trials or admitted with other research drugs within 3 months prior to the trial.
• Any surgical or medical condition which can significantly alter the absorption, distribution, metabolism, or excretion of any study drug.
• Allergy or any contraindications for the study drugs, contrast agents and alcohol.

History of depression, schizophrenia or vascular dementia.

-Refused to sign informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bilateral superselective adrenal arterial embolization; Selectively injects 1.5-2.5 mL ethanol into bilateral adrenal artery to ablate part of the adrenal gland; irbesartanhydrochlorothiazide 162.5 mg/d, amlodipine 5 mg/d	Procedure: BiSAAE; SAAE is a catheter-based percutaneous transluminal procedure which selectively injects ethanol into bilateral adrenal artery to ablate part of the adrenal gland for suppression of excessive aldosterone and catecholamines
Active Comparator: traditional triple antihypertensive treatment; irbesartanhydrochlorothiazide 162.5 mg/d, amlodipine 5 mg/d	Procedure: traditional triple antihypertensive treatment; traditional triple antihypertensive treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of 24-h average systolic blood pressure	Difference in the change of 24-h average systolic blood pressure between the intervention and control group	6-month
Change of 24-h average systolic blood pressure	Difference in the change of 24-h average systolic blood pressure between the intervention and control group	12-month
Change of 24-h average systolic blood pressure	Difference in the change of 24-h average systolic blood pressure between the intervention and control group	3-month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of 24-h average diastolic blood pressure, daytime mean systolic blood pressure, daytime mean diastolic blood pressure, and nighttime average systolic and diastolic blood pressure	Difference in the change of 24-h average diastolic blood pressure, daytime mean systolic blood pressure, daytime mean diastolic blood pressure, and nighttime average systolic and diastolic blood pressure between the intervention and control group	6-month
Change of home systolic and diastolic pressure	Difference in the change of home systolic and diastolic pressure between the intervention and control group	6-month
Change of plasma aldosterone	Difference in the change of plasma aldosterone (pg/mL) between the intervention and control group	6-month
Change of plasma renin measured	Difference in the change of plasma renin (pg/ml) between the intervention and control group	6-month
Change of liver enzymes	Difference in the change of liver enzymes (ALT, AST in IU/L) between the intervention and control group	6-month
Change of kidney function	Difference in the change of serum creatinine in umol/L between the intervention and control group	6-month
Change of fasting blood glucose	Difference in the change of fasting blood glucose in mmol/L between the intervention and control group	6-month
Change of lipids profiles	Difference in the change of lipids profiles (TC, HDL-C, LDL-C, TG) in mmol/L between the intervention and control group	6-month
Change of 24-h urine microalbumin	Difference in the change of 24-h urine microalbumin (mg/L) between the intervention and control group	6-month
Change of echocardiography parameters (IVSd、IVSs、LVPWd, LVPWs, LVEDD)	Difference in the change of echocardiography parameters (IVSd、IVSs、LVPWd, LVPWs, LVEDD, in millimetre[mm]) between the intervention and control group	6-month
Change of carotid intima-media thickness	Difference in the change of carotid intima-media thickness(CIMT) assessed by carotid ultrasound between the intervention and control group	6-month
Change of 24-h average diastolic blood pressure, daytime mean systolic blood pressure, daytime mean diastolic blood pressure, and nighttime average systolic and diastolic blood pressure	Difference in the change of 24-h average diastolic blood pressure, daytime mean systolic blood pressure, daytime mean diastolic blood pressure, and nighttime average systolic and diastolic blood pressure between the intervention and control group	3-month
Change of 24-h average diastolic blood pressure, daytime mean systolic blood pressure, daytime mean diastolic blood pressure, and nighttime average systolic and diastolic blood pressure	Difference in the change of 24-h average diastolic blood pressure, daytime mean systolic blood pressure, daytime mean diastolic blood pressure, and nighttime average systolic and diastolic blood pressure between the intervention and control group	12-month
Change of home systolic and diastolic pressure	Difference in the change of home systolic and diastolic pressure between the intervention and control group	12-month
Change of home systolic and diastolic pressure	Difference in the change of home systolic and diastolic pressure between the intervention and control group	3-month
Difference in the change of office systolic and diastolic pressure between the intervention and control group	Difference in the change of office systolic and diastolic pressure between the intervention and control group	6-month
Difference in the change of office systolic and diastolic pressure between the intervention and control group	Difference in the change of office systolic and diastolic pressure between the intervention and control group	12-month
Difference in the change of office systolic and diastolic pressure between the intervention and control group	Difference in the change of office systolic and diastolic pressure between the intervention and control group	3-month
Difference in the change of blood electrolytes (K+, Na + in mmol/L) between the intervention and control group	Difference in the change of blood electrolytes (K+, Na + in mmol/L) between the intervention and control group	6-month
Difference in the change of blood electrolytes (K+, Na + in mmol/L) between the intervention and control group	Difference in the change of blood electrolytes (K+, Na + in mmol/L) between the intervention and control group	12-month
Difference in the change of blood electrolytes (K+, Na + in mmol/L) between the intervention and control group	Difference in the change of blood electrolytes (K+, Na + in mmol/L) between the intervention and control group	3-month
Change of plasma aldosterone	Difference in the change of plasma aldosterone (pg/mL) between the intervention and control group	12-month
Change of plasma aldosterone	Difference in the change of plasma aldosterone (pg/mL) between the intervention and control group	3-month
Change of plasma cortisol	Change of plasma cortisol	6-month
Change of plasma cortisol	Change of plasma cortisol	12-month
Change of plasma cortisol	Change of plasma cortisol	3-month
Change of plasma renin measured	Difference in the change of plasma renin (pg/ml) between the intervention and control group	12-month
Change of plasma renin measured	Difference in the change of plasma renin (pg/ml) between the intervention and control group	3-month
Change of liver enzymes	Difference in the change of liver enzymes (ALT, AST in IU/L) between the intervention and control group	12-month
Change of liver enzymes	Difference in the change of liver enzymes (ALT, AST in IU/L) between the intervention and control group	3-month
Change of kidney function	Difference in the change of serum creatinine in umol/L between the intervention and control group	12-month
Change of kidney function	Difference in the change of serum creatinine in umol/L between the intervention and control group	3-month
Change of fasting blood glucose	Difference in the change of fasting blood glucose in mmol/L between the intervention and control group	3-month
Change of fasting blood glucose	Difference in the change of fasting blood glucose in mmol/L between the intervention and control group	12-month
Change of lipids profiles	Difference in the change of lipids profiles (TC, HDL-C, LDL-C, TG) in mmol/L between the intervention and control group	12-month
Change of lipids profiles	Difference in the change of lipids profiles (TC, HDL-C, LDL-C, TG) in mmol/L between the intervention and control group	3-month
Change of echocardiography parameters (IVSd、IVSs、LVPWd, LVPWs, LVEDD)	Difference in the change of echocardiography parameters (IVSd、IVSs、LVPWd, LVPWs, LVEDD, in millimetre[mm]) between the intervention and control group	12-month
Change of echocardiography parameters (IVSd、IVSs、LVPWd, LVPWs, LVEDD)	Difference in the change of echocardiography parameters (IVSd、IVSs、LVPWd, LVPWs, LVEDD, in millimetre[mm]) between the intervention and control group	3-month
Change of 24-h urine microalbumin	Difference in the change of 24-h urine microalbumin (mg/L) between the intervention and control group	12-month
Change of 24-h urine microalbumin	Difference in the change of 24-h urine microalbumin (mg/L) between the intervention and control group	3-month
Change of 24-h urine creatinine	Difference in the change of 24-h urine creatinine (umol/L) between the intervention and control group	6-month
Change of 24-h urine creatinine	Difference in the change of 24-h urine creatinine (umol/L) between the intervention and control group	12-month
Change of 24-h urine creatinine	Difference in the change of 24-h urine creatinine (umol/L) between the intervention and control group	3-month
Change of echocardiography parameters (LVEF)	Change of echocardiography parameters (LVEF)	6-month
Change of echocardiography parameters (LVEF)	Change of echocardiography parameters (LVEF)	12-month
Change of echocardiography parameters (LVEF)	Change of echocardiography parameters (LVEF)	3-month
Change of carotid intima-media thickness	Difference in the change of carotid intima-media thickness(CIMT) assessed by carotid ultrasound between the intervention and control group	12-month
Change of carotid intima-media thickness	Difference in the change of carotid intima-media thickness(CIMT) assessed by carotid ultrasound between the intervention and control group	3-month

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Chengdu Medical College

Publications and helpful links

General Publications

• Zhou Y, Liu Q, Wang X, Wan J, Liu S, Luo T, He P, Hou J, Pu J, Wang D, Liang D, Yang Y, Wang P. Adrenal Ablation Versus Mineralocorticoid Receptor Antagonism for the Treatment of Primary Aldosteronism: A Single-Center Prospective Cohort Study. Am J Hypertens. 2022 Dec 8;35(12):1014-1023. doi: 10.1093/ajh/hpac105.
• Wang X, Luo T, Yang Y, Zhou Y, Hou J, Wang P. Unilateral chemical ablation of the adrenal gland lowers blood pressure and alleviates target organ damage in spontaneously hypertensive rats. Hypertens Res. 2023 Dec;46(12):2693-2704. doi: 10.1038/s41440-023-01444-2. Epub 2023 Oct 3.
• Zhou Y, Wang X, Hou J, Wan J, Yang Y, Liu S, Luo T, Liu Q, Xue Q, Wang P. A controlled trial of percutaneous adrenal arterial embolization for hypertension in patients with idiopathic hyperaldosteronism. Hypertens Res. 2024 Feb;47(2):311-321. doi: 10.1038/s41440-023-01420-w. Epub 2023 Aug 29.
• Zhou Y, Wang D, Liu Q, Hou J, Wang P. Case report: Percutaneous adrenal arterial embolization cures resistant hypertension. Front Cardiovasc Med. 2022 Oct 11;9:1013426. doi: 10.3389/fcvm.2022.1013426. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2025
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: February 18, 2024
• First Submitted That Met QC Criteria: February 27, 2024
• First Posted (Actual): February 28, 2024

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Antihypertensive Agents
• Other Study ID Numbers: BiSAAE-RHT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No