Clinical trial NCT06571084: New Screening and Diagnostic Cut-off Points of PA Patients
Official title: Establishment and Clinical Application Evaluation of Screening and Diagnostic Cut-off Points With Aldosterone and Renin for Primary Aldosteronism Patients
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Primary Aldosteronism
Keywords: aldosterone
renin
Primary Aldosteronism
cut-off value
diagnosis
Lead sponsor: China National Center for Cardiovascular Diseases
Sponsor class: OTHER_GOV
Collaborators: name: Beijing Anzhen Hospital
name: First Affiliated Hospital of Chongqing Medical University
name: Chinese Academy of Medical Sciences, Fuwai Hospital
name: Wuhan Asia Heart Hospital
First posted: 2024-08-26
Enrollment: 770
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Preliminary confirmation positive for primary aldosteronism
timeFrame: 1 month
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: Kai-juan Wang
Study officials:
affiliation: Chinese Academy of Medical Sciences, Fuwai Hospital
name: Jun Cai
role: STUDY_CHAIR
affiliation: Chinese Academy of Medical Sciences, Fuwai Hospital
name: Zhou Zhou
role: STUDY_CHAIR
References: