Effects of Adrenal Artery Ablation and Spironolactone in Patients With Primary Aldosteronism

An Open-label, Cohort Study on Effects and Long-term Prognosis of Adrenal Artery Ablation and Spironolactone in Patients With 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.

Current guidelines suggest that surgery and aldosterone receptor inhibitors are the only treatment for primary aldosteronism. However, only about 35% of aldosterone tumors and a small number of unilateral adrenal hyperplasia can be treated surgically. More than 60% of primary aldosteronism and bilateral adrenal hyperplasia need long-term oral aldosterone receptor inhibitors. At present, spironolactone is the most commonly used aldosterone receptor inhibitor. Long term use of spironolactone may cause hyperkalemia, hyperplasia of male mammary gland, hairiness of female and other adverse reactions. Therefore, the researchers suggest that partial removal of adrenals can reduce aldosterone level, lower blood pressure and restore potassium metabolism balance.

In patients with primary hyperaldosteronism, the level of aldosterone increases, which can cause vascular endothelial dysfunction, myocardial injury and ventricular fibrosis. The study shows that long-term oral administration of spironolactone can reverse the above cardiovascular damage and correct heart failure. Adrenal artery ablation can reduce aldosterone level, but the long-term effect on cardiovascular system is unknown. In order to confirm the effect of adrenal artery ablation on blood pressure and cardiovascular system, the researchers conducted an open cohort study on patients with primary aldosteronism (including aldosterone, idiopathic aldosteronism and adrenal hyperplasia). To observe the effect of adrenal artery ablation and spironolactone on blood pressure, blood electrolyte, metabolic index, cardiovascular events and cardiovascular death risk in patients with primary aldosteronism, and to explore its efficacy and safety.

Study Overview

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

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Li Yingsha, MD; Phone Number: 68 13594659454; Email: yslimiss@163.com
• Study Contact Backup: Name: Zhu ZM, MD; Phone Number: 68-023 68767848; Email: zhuzm@yahoo.com

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400042
      • Recruiting
      • The third hospital affiliated to the Army Medical University
      • Contact: Li Yingsha, MD; Phone Number: 68 13594659454; Email: yslimiss@163.com
      • Principal Investigator: Zhu Zhiming, MD

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: Adrenal Artery Ablation; Patients in the Intervention group will be treated with endovascular chemical ablation of adrenal gland by endovascular injection of dehydrated alcohol.	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: Spironolactone; Patients in this group will be treated with aldosterone 20-80mg daily according to blood pressure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of office systolic and diastolic pressure compared with the baseline between two groups	Change of office systolic and diastolic pressure compared with the baseline between the intervention and control group at the end of the study	3 years(End of Trial)
Incidence of major adverse cardiac events (MACE)(%) between two groups	Incidence of major adverse cardiac events (MACE)(%)（cardiac death, myocardial infarction and target vessel revascularisation） between two groups at the end of the study	3 years(End of Trial)

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 two groups at end of the study	3 years(End of Trial)
Change of 24-h average diastolic blood pressure between two groups	Change of 24-h average diastolic blood pressure between two groups at end of the study	3 years(End of Trial)
Change of parameters assessed by echocardiography (IVSd、IVSs、LVPWd, LVPWs, LVEDD, LVEF, LVM) between two groups	Change of parameters assessed by echocardiography (IVSd、IVSs、LVPWd, LVPWs, LVEDD, LVEF, LVM) between two groups at end of the study	3 years(End of Trial)
Change of carotid intima-media thickness assessed by carotid ultrasound between two groups	Change of carotid intima-media thickness assessed by carotid ultrasound between two groups at end of the study	3 years(End of Trial)

Collaborators and Investigators

• Sponsor: Third Military Medical University
• Investigators: Study Director: Zhu ZM, MD, The third militery medical university

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2019
• Primary Completion (ANTICIPATED): December 1, 2022
• Study Completion (ANTICIPATED): June 1, 2023

Study Registration Dates

• First Submitted: February 10, 2020
• First Submitted That Met QC Criteria: May 27, 2020
• First Posted (ACTUAL): June 1, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 1, 2020
• Last Update Submitted That Met QC Criteria: May 27, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Hypertension; Spironolactone; Primary Aldosteronism; Adrenal Artery Ablation
• 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: AAA-S

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