Steroids-Based Screening for Primary Aldosteronism (SAFE)

April 23, 2026 updated by: Qifu Li

This prospective, single-center observational study aims to evaluate whether a steroid-based screening method can more accurately identify Primary Aldosteronism (PA) in hypertensive patients who remain on their usual antihypertensive medications, compared with the conventional aldosterone-to-renin ratio (ARR). PA is a common, potentially curable subtype of secondary hypertension that carries increased cardiovascular risk when undiagnosed or untreated. However, current screening protocols recommend "medication washout" or switching to minimally interfering drugs, which may pose safety concerns and add complexity.

In this study, approximately 406 participants (ages 18-75) with diagnosed hypertension and on at least one interfering antihypertensive drug (such as ACE inhibitors, ARBs, beta-blockers, diuretics, or calcium channel blockers) will be enrolled at the Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University. Each participant will undergo two rounds of blood sampling-first while continuing their usual antihypertensive regimen (the "on-medication" state) and second following a standardized washout/switch period (the "standard state"), if medically feasible. At both stages, levels of plasma aldosterone, renin, and a broad panel of adrenal steroid hormones will be measured by liquid chromatography-tandem mass spectrometry.

By comparing diagnostic performance (e.g., sensitivity, specificity, and area under the receiver operating characteristic curve) of the steroid-based screening versus the ARR, the study seeks to determine whether steroid profiling improves accuracy under real-world treatment conditions. Findings may help refine PA screening strategies, reduce the need for extensive medication adjustments, and contribute to better clinical management of hypertension.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

406

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Qifu Li, MD, PhD, Chief Physician
  • Phone Number: 023-89011554 +8618696676815
  • Email: liqifu@yeah.net

Study Contact Backup

  • Name: Shumin Yang, MD, PhD, Chief Physician
  • Phone Number: 023-89011554 ‭+8615523552235‬
  • Email: 443068494@qq.com

Study Locations

  • China
    • Chongqing Municipality
      • Chongqing, Chongqing Municipality, China, 4000016
        • Recruiting
        • The First Affiliated Hospital of Chongqing Medical University
        • Contact:
        • Contact:
        • Principal Investigator:
          • Qifu Li, MD, PhD, Chief Physician
        • Principal Investigator:
          • Shumin Yang, MD, PhD, Chief Physician
        • Principal Investigator:
          • Jinbo Hu, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

This study will enroll adult patients diagnosed with hypertension (aged 18-75) who are receiving at least one antihypertensive medication that interferes with aldosterone or renin. Participants are recruited from the Endocrinology Outpatient Clinic at The First Affiliated Hospital of Chongqing Medical University between April 2025 and December 2026. All candidates must meet the predefined inclusion criteria (e.g., on interfering antihypertensive drugs for ≥4 weeks) and provide written informed consent. Patients with other confirmed forms of secondary hypertension or severe comorbidities are excluded. The anticipated sample size is approximately 406 participants.

Description

Inclusion Criteria:

  1. Aged 18-75 years, with no sex restriction.
  2. Diagnosed with hypertension, defined as a systolic blood pressure ≥140 mmHg and/or a diastolic blood pressure ≥90 mmHg measured on at least two different days.
  3. Currently receiving at least one antihypertensive medication that interferes with aldosterone or renin (ACEI/ARB, β-blockers, dihydropyridine CCBs, or diuretics including MRA) for ≥4 consecutive weeks.
  4. Fully informed about the study procedures and risks, and willing to participate by signing a written informed consent form.

Exclusion Criteria:

  1. Confirmed secondary hypertension of other etiologies (e.g., renovascular hypertension, renal artery stenosis, reninoma, pheochromocytoma, Cushing's syndrome, Liddle syndrome), excluding obstructive sleep apnea.
  2. Severe cardiac, hepatic, or renal impairment or serious infections, including but not limited to New York Heart Association (NYHA) Class III-IV heart failure, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels exceeding 2.5 times the upper limit of normal, estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m², or severe infections (e.g., diabetic foot, sepsis, pneumonia, refractory infections).
  3. History of major cardiovascular or cerebrovascular events within the past 3 months.
  4. Pregnant or breastfeeding women.
  5. Currently using medications (other than the listed antihypertensives) that may affect aldosterone or renin secretion, including but not limited to sex hormones (e.g., oral contraceptives, estrogen replacement therapy), glucocorticoids (e.g., prednisone, dexamethasone), nonsteroidal anti-inflammatory drugs (NSAIDs, e.g., aspirin, ibuprofen), or antipsychotics (e.g., chlorpromazine, olanzapine).
  6. Individuals lacking or having restricted capacity for independent decision-making or action.
  7. History of psychiatric disorders.
  8. Poor compliance likely to compromise study completion.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
PA Group
Participants with confirmed primary aldosteronism (PA)
Diagnostic test: Steroid-Based Screening (LC-MS/MS)
This diagnostic intervention is a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based steroid profiling assay. It measures a panel of 18 adrenal steroid hormones (e.g., aldosterone, 18-hydroxycortisol, 18-oxocortisol, corticosterone) from plasma samples. In this study, it is used to screen for Primary Aldosteronism (PA) while patients remain on their usual antihypertensive medications. By comparing these steroid profiles against standard aldosterone-renin measurements, the method aims to reduce the need for medication washout and improve diagnostic accuracy for PA.
EH Group
Participants with essential hypertension (EH)
Diagnostic test: Steroid-Based Screening (LC-MS/MS)
This diagnostic intervention is a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based steroid profiling assay. It measures a panel of 18 adrenal steroid hormones (e.g., aldosterone, 18-hydroxycortisol, 18-oxocortisol, corticosterone) from plasma samples. In this study, it is used to screen for Primary Aldosteronism (PA) while patients remain on their usual antihypertensive medications. By comparing these steroid profiles against standard aldosterone-renin measurements, the method aims to reduce the need for medication washout and improve diagnostic accuracy for PA.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Diagnostic Accuracy of Steroid-Based Screening vs. ARR for Primary Aldosteronism in Patients on Antihypertensive Medications
Time Frame: From baseline screening while on medication to completion of confirmatory testing, approximately 4-8 weeks.
The primary outcome is to compare the diagnostic accuracy (e.g., sensitivity, specificity, area under the ROC curve [AUC]) of a steroid-based screening approach with the conventional aldosterone-to-renin ratio (ARR) for identifying primary aldosteronism (PA) in participants who remain on interfering antihypertensive medications (ACE inhibitors, ARBs, beta-blockers, diuretics, or calcium channel blockers). Confirmatory tests (e.g., captopril challenge, saline infusion) in a standard (washed-out) state will be used as the reference standard. A higher AUC or better sensitivity/specificity indicates superior performance.
From baseline screening while on medication to completion of confirmatory testing, approximately 4-8 weeks.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prospective validation of steroid profiling-derived biomarkers and combined strategies for unilateral primary aldosteronism
Time Frame: From enrollment through completion of subtype classification, up to March 2026
Among patients with subtype-confirmed primary aldosteronism, this outcome will assess the diagnostic performance of candidate biomarkers derived from steroid profiling and combined strategies, including approaches integrating adrenal imaging features, for identifying unilateral primary aldosteronism.
From enrollment through completion of subtype classification, up to March 2026

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Qifu Li

Investigators

  • Principal Investigator: Qifu Li, MD, PhD, Chief Physician, First Affiliated Hospital of Chongqing Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 15, 2025

Primary Completion (Estimated)

December 30, 2026

Study Completion (Estimated)

December 30, 2026

Study Registration Dates

First Submitted

April 16, 2025

First Submitted That Met QC Criteria

April 16, 2025

First Posted (Actual)

April 23, 2025

Study Record Updates

Last Update Posted (Actual)

April 28, 2026

Last Update Submitted That Met QC Criteria

April 23, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SAFE Study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

We do not intend to share individual participant data from this study due to concerns regarding participant privacy, regulatory constraints, and the limited scope of the current study. Aggregated or summary results will be made publicly available through publication or the results section on ClinicalTrials.gov.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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