Prospective Study Assessing Blood Pressure and Other Outcomes Post-treatment in Patients With Primary Aldosteronism (PA_PACES)

Prospective Study Assessing Blood Pressure, Cardiovascular, Endothelial and Other Outcomes poSt-surgical and Medical Treatment in Patients With Primary Aldosteronism

Majority of patients with hypertension have primary hypertension (without an underlying cause). Secondary hypertension (due to an underlying disease) is important to recognize, as treatment can lead to cure of hypertension. Primary aldosteronism (PA) is the most common cause of secondary hypertension, and can be found in 5-10% of patients locally.

PA is caused by excessive release of a hormone (aldosterone) from the adrenal glands, which can be unilateral (one gland) or bilateral (both glands). Distinction between two is crucial as unilateral disease is treated with the aim of cure by surgery, and bilateral disease is treated by medication.

It has been shown that excess aldosterone has other harmful effects in addition to hypertension, such as directly affecting the heart, blood vessels, kidneys, diabetes and quality of life. This is supported by studies showing reversal of these effects after treatment for PA. In addition, improvements after surgery appears to be superior to medical treatment, although studies have found variable results.

Hence, the investigators aim to accurately subtype patients with PA into unilateral or bilateral disease and study the post-treatment response after both surgery and medicine with regards to the effects on blood pressure, cardiovascular, renal, metabolic and quality of life.

Study Overview

• Status: Completed
• Conditions: Primary Aldosteronism; Primary Aldosteronism Due to Aldosterone Producing Adenoma; Primary Aldosteronism Due to Adrenal Hyperplasia (Bilateral)
• Intervention / Treatment: Drug: Mineralocorticoid Receptor Antagonists; Procedure: Adrenalectomy

• Study Type: Observational
• Enrollment (Actual): 57

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 529889
    • Changi General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with confirmed primary aldosteronism

Description

Inclusion Criteria:

i. Legally capacitated ii. 21-80 years iii. Diagnosed with primary aldosteronism iv. Patient is willing, or has undergone, adrenal surgery (in case of unilateral disease), or medical treatment (if not keen for surgery, medically unfit, or has bilateral disease)

Exclusion Criteria:

i. Unable to give consent ii. < 21 years or > 80 years iii. Glucocorticoid remediable aldosteronism iv. Adrenal Carcinoma v. Severe or terminal medical condition(s) that in the view of the investigator prohibits participation in the study or interferes with possible treatment or health-related quality of life, e.g. cancer, end-stage liver disease, end stage renal failure vi. Female patients who are pregnant, intending to become pregnant or breastfeeding

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Medical Treatment; Patients who undergo medical treatment, in view of bilateral PA, or unilateral PA not keen for surgery, or indeterminate (lack of localisation on tests)	Drug: Mineralocorticoid Receptor Antagonists; Medical treatment with MRA / amiloride; Other Names: Eplerenone; Spironolactone; Amiloride
Surgical Treatment; Patients with unilateral PA who underwent adrenalectomy	Procedure: Adrenalectomy; Adrenalectomy for unilateral adrenal hyperplasia / adenoma

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Pressure	Blood pressure assessed by 24hr ambulatory BP	Change from Baseline Blood Pressure at 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Use of antihypertension medications	Use of antihypertension medications as expressed in daily defined dosages and total number of medications	Change from Baseline Antihypertension medications at 12 months
Blood Pressure	Clinic blood pressure	Change from Baseline Clinic Blood Pressure at 12 months
Cardiac function	Cardiac function using 2DE	Change from Baseline Cardiac function at 12 months.
Left ventricular hypertrophy	as assessed by 2DE and ECG	Change from Baseline Left ventricular hypertrophy at 12 months
Renal Function	change in serum creatinine, calculated GFR, albuminuria (prevalence and severity)	Change from Baseline Renal Function at 12 months
Quality of Life (RAND-36)	RAND-36	Change from Baseline Quality of Life RAND-36 at 12 months
Quality of Life ( Beck's depression inventory II)	Beck's depression inventory II	Change from Baseline Quality of Life (BDI-II) at 12 months
Quality of Life (EQ5D)	EQ5D	Change from Baseline EQ5D at 12 months
Lipids	Lipids	Change from Baseline Lipids at 12 months
Transaminitis	ALT, AST,	Change from Baseline transaminitis at 12 months
Insulin Resistance	Measured with HOMA	Change from Baseline Insulin resistance at 12 months
Fasting glucose	Fasting glucose	Change from Baseline Fasting glucose at 12 months
weight	change in weight	Change from Baseline weight at 12 months
Control of hypertension	Proportion of patients reaching normal BP (ambulatory /home BP <135/85 or clinic BP <140/90)	Change from Baseline Status of hypertension control at 12 months
Cure of Primary aldosteronism	Proportion of patients with cure of PA after adrenalectomy	Change from Baseline Status of primary aldosteronism at 12 months

Collaborators and Investigators

• Sponsor: Changi General Hospital
• Investigators: Principal Investigator: Troy Puar, MRCP (UK), Changi General Hospital

Publications and helpful links

General Publications

• Puar TH, Cheong CK, Foo RSY, Saffari SE, Tu TM, Chee MR, Zhang M, Ng KS, Wong KM, Wong A, Ng FC, Aw TC, Khoo J, Gani L, King T, Loh WJ, Soh SB, Au V, Tay TL, Tan E, Mae L, Yew J, Tan YK, Tong KL, Lee S, Chai SC. Treatment of Primary Aldosteronism and Reversal of Renin Suppression Improves Left Ventricular Systolic Function. Front Endocrinol (Lausanne). 2022 Jun 30;13:916744. doi: 10.3389/fendo.2022.916744. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 20, 2017
• Primary Completion (ACTUAL): October 20, 2019
• Study Completion (ACTUAL): September 20, 2020

Study Registration Dates

• First Submitted: May 26, 2017
• First Submitted That Met QC Criteria: May 31, 2017
• First Posted (ACTUAL): June 5, 2017

Study Record Updates

• Last Update Posted (ACTUAL): May 20, 2022
• Last Update Submitted That Met QC Criteria: May 19, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Cardiovascular; Blood pressure; Renal; Primary aldosteronism; Endothelial; Adrenalectomy; Mineralocorticoid-receptor Antagonists
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Gonadal Disorders; Disorders of Sex Development; Urogenital Abnormalities; Congenital Abnormalities; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Steroid Metabolism, Inborn Errors; Adenoma; Hyperplasia; Hyperaldosteronism; Adrenal Hyperplasia, Congenital; Adrenogenital Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Channel Blockers; Hormone Antagonists; Diuretics, Potassium Sparing; Acid Sensing Ion Channel Blockers; Epithelial Sodium Channel Blockers; Spironolactone; Mineralocorticoid Receptor Antagonists; Eplerenone; Mineralocorticoids; Amiloride
• Other Study ID Numbers: PA_PACES; CHF2016.02-P (OTHER_GRANT: Changi Health Fund (Ltd))

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