New Screening and Diagnostic Cut-off Points of PA Patients

Establishment and Clinical Application Evaluation of Screening and Diagnostic Cut-off Points With Aldosterone and Renin for Primary Aldosteronism Patients

This study aims to establish the screening and diagnostic cut-off points for primary aldosteronism patients by a novel small molecule "sandwich method" aldosterone and renin chemiluminescent immunoassay.

Study Overview

• Status: Recruiting
• Conditions: Primary Aldosteronism

Detailed Description

Primary aldosteronism (PA) is the most common causes of secondary hypertension. The diagnostic workup for PA is composed of multiple steps and requires measurement of both plasma aldosterone and renin. In terms of assay of aldosterone, most of currently available chemiluminescence assays are based on competitive methods. What is actually detected is the sum of aldosterone and its metabolite aldosterone 3C glucuronide, which causes the value to be about 50%~100% higher than the actual value. This study aims to establish a new ARR (aldosterone/renin ratio) cutoff point for PA screening and a new cutoff point for PA diagnosis, using a recently developed two-site sandwich chemiluminescence method (Snibe, China) for aldosterone and renin assay.

Hypertensive patients referred to hospitals for screening of PA will be included. All the participants proceed to seated saline infusion test (SIT) and captopril challenge test (CCT) for confirmation. Aldosterone and renin will be measured using chemiluminescent immunoassay on the Liaison analyzer (DiaSorin, Italy) and MAGLUMI X8 (Snibe, China), as well as liquid chromatography-tandem mass spectrometry (LC-MS/MS) platform. According to the experience of Fuwai Hospital, the following diagnosis criteria are proposed: Based on the results of currently used (DiaSorin, Italy), aldosterone > 8.5ng/dL and renin < 15μIU/mL after sitting saline infusion conform PA, and aldosterone ≤ 8.5ng/dL excludes PA.

The total number of cases to be enrolled in this study is planned to be 770, including at least 77 positive subjects and at least 406 negative subjects. By drawing the ROC curve, the point corresponding to the maximum value of the Youden index will be selected as the cutoff value, and the corresponding sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, etc. will be calculated.

• Study Type: Observational
• Enrollment (Estimated): 770

Contacts and Locations

• Study Contact: Name: Jun Cai; Email: caijun7879@126.com
• Study Contact Backup: Name: Zhou Zhou; Phone Number: +86 10 88398055; Email: zhouzhou@fuwaihospital.org

Study Locations

• China
  • Beijing, China, 100037
    • Recruiting
    • Kai-juan Wang
    • Contact: Kai-juan Wang; Phone Number: +86 10 88322021; Email: wkaijuan@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients aged 18-75 years old and highly suspected primary aldosteronism will be included. Patients will be excluded if who is secondary hypertension other than PA, chronic cardiac dysfunction (NYHA III-IV), medium and several kidney dysfunction (Ccr<30ml/min), with history of liver cirrhosis, oncosis and recent use of steroids or oral contraceptives, pregnant or lactating.

Description

Inclusion Criteria:

• 18-75y;
• persistent hypertension (BP >150/100 mm Hg), or drug-resistant hypertension;
• newly diagnosed hypertension;
• hypertension and spontaneous or diuretic-induced hypokalemia;
• hypertension with adrenal incidentaloma;
• hypertension and a family history of early-onset hypertension or cerebrovascular accident at a young age (<40 years);
• status as a hypertensive first-degree relative of patients with PA;
• patients with hypertension and obstructive sleep apnea.

Exclusion Criteria:

• age <18; BMI ≤ 18.0kg/m2 or ≥ 35.0 kg/m2;
• a diagnosis of secondary hypertension other than PA;
• chronic cardiac dysfunction (NYHA III-IV);
• medium and several kidney dysfunction (Ccr<30ml/min);
• liver cirrhosis;
• terminal malignant tumor;
• recent use of steroids or oral contraceptives;
• pregnancy or lactation.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

suspected PA; Patients with a high risk for PA who were willing to participate in the study were recruited. The inclusion criteria1 were as follows: persistent hypertension (BP >150/100 mm Hg), or drug-resistant hypertension; newly diagnosed hypertension; hypertension and spontaneous or diuretic-induced hypokalemia; hypertension with adrenal incidentaloma; hypertension and a family history of early-onset hypertension or cerebrovascular accident at a young age (<40 years); or status as a hypertensive first-degree relative of patients with PA; patients with hypertension and obstructive sleep apnea.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preliminary confirmation positive for primary aldosteronism	Aldosterone ≥ 85pg/ml after sitting saline test	1 month

Collaborators and Investigators

• Sponsor: China National Center for Cardiovascular Diseases
• Collaborators: Beijing Anzhen Hospital; Wuhan Asia Heart Hospital; First Affiliated Hospital of Chongqing Medical University; Fuwai Central China Cardiovascular Hospital; Fuwai shenzhen hospital，chinese academy of medical sciences; Fuwai yunnan hospital，chinese academy of medical sciences
• Investigators: Study Chair: Jun Cai, Chinese Academy of Medical Sciences, Fuwai Hospital; Study Chair: Zhou Zhou, Chinese Academy of Medical Sciences, Fuwai Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2024
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: August 22, 2024
• First Submitted That Met QC Criteria: August 22, 2024
• First Posted (Actual): August 26, 2024

Study Record Updates

• Last Update Posted (Actual): August 26, 2024
• Last Update Submitted That Met QC Criteria: August 22, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: diagnosis; aldosterone; renin; Primary Aldosteronism; cut-off value
• Additional Relevant MeSH Terms: Endocrine System Diseases; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Hyperaldosteronism
• Other Study ID Numbers: 2023-2260

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