Adrenal Artery Ablation Treats Primary Aldosteronism

An Open-label, Prospective, Controlled Clinical Trial on Effects and Safety of Adrenal Artery Ablation (Triple A) for Primary Aldosteronism

Primary aldosteronism (PA) is one of the most common cause of endocrine and resistant hypertension. Current studies have shown that the activation of the renin-angiotensin-aldosterone system (RAAS) and the increased sympathetic nerve activity in the central or local tissue are the key mechanisms of high blood pressure and its organ damages.

The classical method for diagnosis of primary aldosteronism depends on the detection of peripheral venous blood aldosterone level, which is incapable of accurate positioning diagnosis. On the other hand, the current guidelines recommend that surgery and aldosterone receptor inhibitors were the only treatment for primary aldosteronism. However, only about 35% of aldosterone tumors and a small part of unilateral adrenal hyperplasia can be treated by surgery. More than 60% of idiopathic aldosteronism and bilateral adrenal hyperplasia need long-term drug therapy. However, long-term aldosterone inhibitor treatment may also cause hyperkalemia, male breast hyperplasia, female hirsutism and other adverse reactions.

Therefore, the investigators proposed that endovascular chemical partial ablation of the adrenal gland can lower the aldosterone level, reduce the blood pressure and recover the potassium metabolism balance. In order to confirm the above effects, the investigators conduct an open, prospective, positive controlled study in patients with primary aldosteronism patients (including aldosterone, idiopathic aldosteronism and adrenal hyperplasia). The effects on blood pressure, blood electrolytes, adrenal hormones, metabolic indexes, target organ damages were observed to explore the efficacy and safety of the endovascular ablation of the adrenal gland in the treatment of primary aldosteronism.

Study Overview

• Status: Completed
• Conditions: Hypertension; Primary Aldosteronism
• Intervention / Treatment: Procedure: Endovascular chemical Ablation of Adrenal Gland

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400042
      • The third hospital affiliated to the Third Military Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Primary Aldosteronis diagnosed by increased Renin ratio (ARR) and serum aldosterone levels ≥15 ng / dl, and confirmed by saline injection test or captopril inhibition test.
• Idiopathic aldosteronism, bilateral adrenal hyperplasia, and unilateral adrenal hyperplasia with no superior secretion confirmed with adrenal CT and adrenal venous blood (AVS).
• The patients was diagnosed with aldosteronoma or unilateral adrenal hyperplasia but refused to surgical excision.
• Signed informed consent and agreed to participate in this study.

Exclusion Criteria:

• Aldosterone cancer.
• Hyperkalemia.
• Renal failure or the following history of nephropathy: serum creatinine 1.5 times higher than the upper limit; dialysis history; or nephrotic syndrome.
• Secondary hypertension except the primary aldosteronism.
• Adrenergic insufficiency.
• 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 2 times higher than the upper limit, liver cirrhosis, history of hepatic encephalopathy, esophageal variceal history or portal shunt history.
• 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.
• Refused to sign informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Intevention; Adrenal Artery Ablation	Procedure: Endovascular chemical Ablation of Adrenal Gland; Patients in this group will be treated with partial ablation of adrenal gland by endovascular injection of dehydrated alcohol.
NO_INTERVENTION: Control; No intervention, but treated with standard anti-hypertensive drigs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of 24-h average systolic blood pressure compared with the baseline	Change of 24-h average systolic blood pressure compared with the baseline at the end of the study (24 weeks) in the intervention group.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of 24-h average systolic blood pressure between two groups	Change of 24-h average systolic blood pressure between the intervention and control group at the end of the study (24 weeks)	24 weeks
Change of anti-hypertensive regimen between two groups	Change of number, classes, and combinations of classes of antihypertensive drugs between the intervention and control group at the end of the study (24 weeks)	24 weeks
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 two groups	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 at the end of the study (24 weeks)	24 weeks
Change of office systolic and diastolic pressure between two groups	Change of office systolic and diastolic pressure between the intervention and control group at the end of the study (24 weeks)	24 weeks
Change of blood electrolytes（serum potassium and natrium in mmol/L）	Change of blood electrolytes（serum potassium and natrium in mmol/L） compared with baseline, and between the intervention and control group at the end of the study (24 weeks)	24 weeks
Change of plasma aldosterone and 24-h urine aldosterone	Change of plasma aldosterone and 24-h urine aldosterone compared with baseline, and between the intervention and control group at the end of the study (24 weeks)	24 weeks
Change of plasma renin	Change of plasma renin compared with baseline, and between the intervention and control group at the end of the study (24 weeks)	24 weeks
Change of plasma cortisol and 24-h urine cortisol	Change of plasma cortisol and 24-h urine cortisol compared with baseline, and between the intervention and control group at the end of the study (24 weeks)	24 weeks
Change of liver enzymes (ALT, AST)	Change of liver enzymes (ALT, AST) compared with baseline, and between the intervention and control group at the end of the study (24 weeks)	24 weeks
Change of serum creatinine	Change of serum creatinine compared with baseline, and between the intervention and control group at the end of the study (24 weeks)	24 weeks
Change of fasting blood glucose	Change of fasting blood glucose in mmol/L compared with baseline, and between the intervention and control group at the end of the study (24 weeks)	24 weeks
Change of lipids profiles (TC, HDL-C, LDL-C, TG) in mmol/L	Change of lipids profiles (Total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride) in mmol/L compared with baseline, and between the intervention and control group at the end of the study (24 weeks)	24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of testosterone and estrogen levels	Change of testosterone and estrogen levels compared with baseline, and between the intervention and control group at the end of the study (24 weeks)	24 weeks
Change of 24-h urine microalbumin, microalbumin/creatinine ratio	Change of 24-h urine microalbumin, microalbumin/creatinine ratio compared with baseline, and between the intervention and control group at the end of the study (24 weeks)	24 weeks
Change of parameters assessed by echocardiography (IVSd、IVSs、LVPWd, LVPWs, LVEDD, LVEF, LVM)	Change of parameters assessed by echocardiography (IVSd、IVSs、LVPWd, LVPWs, LVEDD, LVEF, LVM) compared with baseline, and between the intervention and control group at the end of the study (24 weeks)	24 weeks
Change of carotid intima-media thickness assessed by carotid ultrasound	Change of carotid intima-media thickness(CIMT) assessed by carotid ultrasound compared with baseline, and between the intervention and control group at the end of the study (24 weeks)	24 weeks
Change of electrocardiogram manifestations	Change of electrocardiogram manifestations(heart rhythms, heart rates and arrhythmia ) compared with baseline, and between the intervention and control group at the end of the study (24 weeks)	24 weeks

Collaborators and Investigators

• Sponsor: Third Military Medical University

Publications and helpful links

General Publications

• Sun F, Hong Y, Zhang H, Liu X, Zhao Z, He H, Yan Z, Zhu Z. Determination of adrenal hypersecretion in primary Aldosteronism without aldosterone-production adenomas. BMC Endocr Disord. 2021 May 31;21(1):114. doi: 10.1186/s12902-021-00770-1.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2017
• Primary Completion (ACTUAL): December 31, 2018
• Study Completion (ACTUAL): June 30, 2019

Study Registration Dates

• First Submitted: December 24, 2017
• First Submitted That Met QC Criteria: January 6, 2018
• First Posted (ACTUAL): January 12, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 8, 2019
• Last Update Submitted That Met QC Criteria: July 3, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Hypertension; Ablation; Adrenal Gland; Primary Aldosteronism
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Endocrine System Diseases; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Hypertension; Hyperaldosteronism; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-Agonists; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Epinephrine; Racepinephrine; Epinephryl borate
• Other Study ID Numbers: Triple A-PA

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