Effectiveness and Safety of BiSAAE for Resistant Hypertension.

Official title

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

Overview

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.

Interventions

• 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
• Procedure traditional triple antihypertensive treatment
  traditional triple antihypertensive treatment

Primary outcome measures

• Change of 24-h average systolic blood pressure [Time frame: 6-month]
• Change of 24-h average systolic blood pressure [Time frame: 12-month]
• Change of 24-h average systolic blood pressure [Time frame: 3-month]

Secondary outcome measures (12)

• 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 [Time frame: 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 [Time frame: 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 [Time frame: 12-month]
• Change of home systolic and diastolic pressure [Time frame: 6-month]
• Change of home systolic and diastolic pressure [Time frame: 12-month]
• Change of home systolic and diastolic pressure [Time frame: 3-month]
• Difference in the change of office systolic and diastolic pressure between the intervention and control group [Time frame: 6-month]
• Difference in the change of office systolic and diastolic pressure between the intervention and control group [Time frame: 12-month]
• Difference in the change of office systolic and diastolic pressure between the intervention and control group [Time frame: 3-month]
• Difference in the change of blood electrolytes (K+, Na + in mmol/L) between the intervention and control group [Time frame: 6-month]
• Difference in the change of blood electrolytes (K+, Na + in mmol/L) between the intervention and control group [Time frame: 12-month]
• Difference in the change of blood electrolytes (K+, Na + in mmol/L) between the intervention and control group [Time frame: 3-month]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• 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. PMID 37789113
• 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. PMID 37644179
• 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. PMID 36304542
• 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. PMID 36205513

Identifiers

NCT: NCT06282107 · BiSAAE-RHT

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗