Superselective Adrenal Arterial Embolization for Resistant Hypertension

Effectiveness and Safety of Superselective Adrenal Arterial Embolization (SAAE) for Resistant Hypertension: A Randomized, Parallel, Controlled Clinical Trial

Resistant hypertension (RH) is usually defined as blood pressure (BP) that remains above guideline-specified targets despite the use of three or more antihypertensive agents at optimal or maximally tolerated doses, with one of those agents preferably being a diuretic. It is not uncommon, being identified in 10 to 30% of hypertensive patients and it is known to be a risk factor for cardiovascular (CV) events, including stroke, myocardial infarction (MI), heart failure (HF), and CV mortality, as well as adverse renal events,including chronic kidney disease (CKD) and end-stage kidney disease (ESKD). The activation of the renin-angiotensin-aldosterone system (RAAS) and sympatho-adrenomedullary system can play a pathogenic role in triggering and sustaining RH. 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. Therefore, SAAE is a minimally invasive procedure that might be used as an alternative strategy to antihypertensive drugs or reduce the intensity of antihypertensive drugs.

Study Overview

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

Detailed Description

Not Provided

• Study Type: Interventional
• Enrollment (Anticipated): 144
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yaqiong Zhou, MD; Phone Number: +8615184399329; Email: 1273868593@qq.com
• Study Contact Backup: Name: Yanqiu M Yang; Phone Number: +8617380086816; Email: 285965467@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female, aged between 18-65 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: Superselective adrenal arterial embolization; Selectively injects ethanol into adrenal artery to ablate part of the adrenal gland Interventions: Procedure: superselective adrenal arterial embolization Drug: traditional triple antihypertensive treatment	Procedure: SAAE; 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; Drug: traditional triple antihypertensive treatment; irbesartanhydrochlorothiazide 162.5 mg/d, amlodipine 5 mg/d
Active Comparator: Traditional triple antihypertensive treatment; No intervention, but treated with traditional triple antihypertensive treatment	Drug: traditional triple antihypertensive treatment; irbesartanhydrochlorothiazide 162.5 mg/d, amlodipine 5 mg/d

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

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 the number of antihypertensive medications	Difference in the change of the number of antihypertensive medications 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 office systolic and diastolic pressure	Difference in the change of office systolic and diastolic pressure between the intervention and control group	6-month
Change of blood electrolytes (K+, Na +)	Difference in the change of blood electrolytes (K+, Na + in mmol/L) 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 cortisol	Difference in the change of plasma cortisol (nmol/L) 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 24-h 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 echocardiography parameters (LVEF)	Difference in the change of cardiac parameters assessed by echocardiography LVEF (%) 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

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Chengdu Medical College
• Investigators: Study Chair: Peijian Wang, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College

Publications and helpful links

General Publications

• Bourque G, Hiremath S. Rethinking Resistant Hypertension. J Clin Med. 2022 Mar 7;11(5):1455. doi: 10.3390/jcm11051455.
• Dong H, Zou Y, He J, Deng Y, Chen Y, Song L, Xu B, Gao R, Jiang X. Superselective adrenal arterial embolization for idiopathic hyperaldosteronism: 12-month results from a proof-of-principle trial. Catheter Cardiovasc Interv. 2021 May 1;97 Suppl 2:976-981. doi: 10.1002/ccd.29554. Epub 2021 Feb 19.
• Giurazza F, Corvino F, Silvestre M, Cangiano G, Cavaglia E, Amodio F, De Magistris G, Frauenfelder G, Niola R. Adrenal glands hemorrhages: embolization in acute setting. Gland Surg. 2019 Apr;8(2):115-122. doi: 10.21037/gs.2018.10.06.
• Zhou Q, Liu X, Zhang H, Zhao Z, Li Q, He H, Zhu Z, Yan Z. Adrenal Artery Ablation for the Treatment of Hypercortisolism Based on Adrenal Venous Sampling: A Potential Therapeutic Strategy. Diabetes Metab Syndr Obes. 2020 Oct 6;13:3519-3525. doi: 10.2147/DMSO.S262092. eCollection 2020.
• Zhao Z, Liu X, Zhang H, Li Q, He H, Yan Z, Sun F, Li Y, Zhou X, Bu X, Wu H, Shen R, Zheng H, Yang G, Zhu Z; Chongqing Endocrine Hypertension Collaborative Team. Catheter-Based Adrenal Ablation Remits Primary Aldosteronism: A Randomized Medication-Controlled Trial. Circulation. 2021 Aug 17;144(7):580-582. doi: 10.1161/CIRCULATIONAHA.121.054318. Epub 2021 Aug 16. No abstract available.

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2022
• Primary Completion (Anticipated): October 1, 2024
• Study Completion (Anticipated): March 31, 2025

Study Registration Dates

• First Submitted: September 11, 2022
• First Submitted That Met QC Criteria: September 20, 2022
• First Posted (Actual): September 23, 2022

Study Record Updates

• Last Update Posted (Actual): September 23, 2022
• Last Update Submitted That Met QC Criteria: September 20, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

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