Adrenal Artery Ablation for Primary Aldosteronism

Adrenal Artery Ablation for Primary Aldosteronism：A Randomized, Parallel, Active-controlled Clinical Trial to Evaluate the Efficacy and Safety of Adrenal Artery Ablation（AAA）in the Treatment of Primary Aldosteronism

Primary aldosteronism (PA) is one of the most common causes 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: Unknown
• Conditions: Hypertension; Primary Aldosteronism
• Intervention / Treatment: Procedure: Endovascular chemical Ablation of Adrenal Gland; Drug: Sequenced antihypertensvie drugs with titrated dosage

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Chongqing, China, 400042
    • Recruiting
    • The third hospital affiliated to the Third Military Medical University
    • Contact: Zhiming Zhu, MD, PhD; Phone Number: 86-023-68705094; Email: zhuzm@yahoo.com
    • Principal Investigator: Zhiming Zhu, MD, PhD
  • Chongqing
    • Chongqing, Chongqing, China, 400042
      • Recruiting
      • The third hospital affiliated to the Third Military Medical University
      • Contact: Hongbo He, MD.; Phone Number: 86-23-68757880; Email: cqhehongbo@gmail.com
      • Principal Investigator: Zhiming Zhu, MD.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 26 years to 56 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 were 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 3 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: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intevention; Patients in this group will be treated with endovascular chemical ablation of adrenal glandp by endovascular injection of dehydrated alcohol. Sequenced antihypertensvie drugs with titrated dosage(amlodipine 5-10 mg/d ; terazosin 2-6mg/d) will be prescribed if home blood pressure (HBP) exceeds ≥160/100 mmHg.	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.; Drug: Sequenced antihypertensvie drugs with titrated dosage; Patients will be treated with different antihypertensive drugs in two groups.
Active Comparator: Control; Patients in this group will be treated only with sequenced antihypertensvie drugs with titrated dosage(amlodipine 5mg/d→plus spironolactone 20 mg/d→plus spironolactone 40 mg/d→plus spironolactone 60 mg/d→→plus amlodipine 10 mg/ d →plus terazosin 2-6mg / d) if home blood pressure (HBP) exceeds ≥160/100 mmHg.	Drug: Sequenced antihypertensvie drugs with titrated dosage; Patients will be treated with different antihypertensive drugs in two groups.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of 24-h average systolic blood pressure measured at baseline and the end of the trial	Difference in the change of 24-h average systolic blood pressure compared with the baseline at the end of the study (24 weeks) between the intervention and control group is to be analysed.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of blood electrolytes（serum potassium and natrium in mmol/L）measured at baseline and the end of the trial	Difference in the change of blood electrolytes（serum potassium and natrium in mmol/L) compared with the baseline at the end of the study (24 weeks) between the intervention and control group is to be analysed.	24 weeks
Change of plasma aldosterone and 24-h urine aldosterone measured at baseline and the end of the trial	Difference in the change of plasma aldosterone and 24-h urine aldosterone compared with the baseline at the end of the study (24 weeks) between the intervention and control group is to be analysed.	24 weeks
Change of plasma renin measured at baseline and the end of the trial	Difference in the change of plasma renin compared with the baseline at the end of the study (24 weeks) between the intervention and control group is to be analysed.	24 weeks
Change of 24-h average systolic blood pressure measured at the end of the trial 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
Change of anti-hypertensive regimen assessed at baseline and the end of the trial	Difference in the change of anti-hypertensive regimen compared with the baseline at the end of the study (24 weeks) between the intervention and control group is to be analysed.	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 measured at baseline and the end of the trial	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 compared with the baseline at the end of the study (24 weeks) between the intervention and control group is to be analysed.	24 weeks
Change of home systolic and diastolic pressure measured at baseline and the end of the trial	Difference in the change of home systolic and diastolic pressure compared with the baseline at the end of the study (24 weeks) between the intervention and control group is to be analysed.	24 weeks
Change of office systolic and diastolic pressure measured at baseline and the end of the trial	Difference in the change of office systolic and diastolic pressure compared with the baseline at the end of the study (24 weeks) between the intervention and control group is to be analysed.	24 weeks
Change of liver enzymes measured at baseline and the end of the trial	Difference in the change of liver enzymes (ALT, AST in IU/L) compared with the baseline at the end of the study (24 weeks) between the intervention and control group is to be analysed.	24 weeks
Change of kidney function measured at baseline and the end of the trial	Difference in the change of serum creatinine in umol/L compared with the baseline at the end of the study (24 weeks) between the intervention and control group is to be analysed.	24 weeks
Change of fasting blood glucose and lipids profiles measured at baseline and the end of the trial	Difference in the change of fasting blood glucose and lipids profiles (TC, HDL-C, LDL-C, TG) in mmol/L compared with the baseline at the end of the study (24 weeks) between the intervention and control group is to be analysed.	24 weeks
Change of sex hormones measured at baseline and the end of the trial	Difference in the change of 17-OH, DHEAS, testosterone and estrogen levels compared with the baseline at the end of the study (24 weeks) between the intervention and control group is to be analysed.	24 weeks
Change of 24-h urine microalbumin, microalbumin/creatinine ratio measured at baseline and the end of the trial	Difference in the change of 24-h urine microalbumin, microalbumin/creatinine ratio compared with the baseline at the end of the study (24 weeks) between the intervention and control group is to be analysed.	24 weeks
Change of cardiac parameters assessed by echocardiography (IVSd、IVSs、LVPWd, LVPWs, LVEDD, LVEF, LVM) measured at baseline and the end of the trial	Difference in the change of cardiac parameters assessed by echocardiography (IVSd、IVSs、LVPWd, LVPWs, LVEDD, in millimetre(mm), and LVEF(%), LVM in gram) compared with the baseline at the end of the study (24 weeks) between the intervention and control group is to be analysed.	24 weeks
Change of carotid intima-media thickness assessed by carotid ultrasound at baseline and the end of the trial	Difference in the change of carotid intima-media thickness(CIMT) in millimetre(mm) compared with the baseline at the end of the study (24 weeks) between the intervention and control group is to be analysed.	24 weeks

Collaborators and Investigators

• Sponsor: Third Military Medical University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2018
• Primary Completion (Anticipated): July 1, 2019
• Study Completion (Anticipated): January 1, 2020

Study Registration Dates

• First Submitted: June 7, 2018
• First Submitted That Met QC Criteria: August 28, 2018
• First Posted (Actual): August 31, 2018

Study Record Updates

• Last Update Posted (Actual): August 31, 2018
• Last Update Submitted That Met QC Criteria: August 28, 2018
• Last Verified: August 1, 2018

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: AAA-PA

Drug and device information, study documents

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