Clinical trial NCT05959863: Primary Aldosteronism LC-MS/MS-specific Cutoffs
Official title: LC-MS/MS-specific Cutoffs for Screening and Confirmatory Testing of Primary Aldosteronism: A Multi-center Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Primary Aldosteronism
Keywords: Diagnostic
Multicenter study
Lead sponsor: Chongqing Medical University
Sponsor class: OTHER
Collaborators: name: Chinese PLA General Hospital
name: Chinese Academy of Medical Sciences, Fuwai Hospital
name: Tianjin Medical University General Hospital
First posted: 2023-07-25
Enrollment: 396
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: This study intends to include patients taking hypertension medication at each center between June 2023 and July 2024 with subjects signing written informed consent.

Brief summary: Aims to evaluation the LC-MS/MS-specific cutoffs of PA screening and CCT test.

Detailed description: Plasma aldosterone concentration and plasma renin activity / concentration measurement are important for early screening and diagnosis of Primary Aldosteronism (PA), most measurement methods are currently based on chemiluminescence, which may be cross-reactivity with other compounds and metabolites, leading to misdiagnosis or missed diagnosis of PA patients. Liquid chromatography tandem mass spectrometry (LC-MS/MS) has been introduced into the clinical routine analysis of steroid hormones due to its higher specificity and is increasingly used for the diagnosis of adrenal diseases. However, it is unknown for the cut-offs of PA screening and CCT test based on this technology in China. Therefore, the purpose of this study is to establish the screening and CCT cut-off point for primary aldosteronism based on LC-MS/MS technique at multicenter in China.

Eligibility criteria: Inclusion Criteria:

1. Age is between 18-75 years old.
2. Hypertension patients with high risk factors for PA (meeting one of the following criteria): a.Persistent hypertension (\> 150 / 100mmHg); b. Refractory hypertension (combined with 3 antihypertensive drugs and one used as a diuretic,Blood pressure is still greater than 140 / 90 mmHg or four antihypertensive drugs are needed to control blood pressure of less than 140 / 90 mmHg); c.Hypertension with adrenal accidental tumor; d.Hypertension is associated with hypokalaemia;
3. Recent and stable use of antihypertensive drugs for more than 2 weeks, The drug types may include: β receptor blockers, CCB(calcium channel blockers), angiotension converting enzyme inhibitors(ACEi), Angiotensin Receptor Blocker(ARB), mineralocorticoid receptor antagonists(MRA), and other diuretics.

Exclusion Criteria:

1. Patients who are unwilling to participate and complete the study or refuse to sign a written informed consent for the study;
2. Patients diagnosed with other secondary hypertension (such as renal hypertension, renal artery stenosis, pheochromocytoma, Cushing's syndrome, etc.);
3. Combined with severe renal insufficiency eGFR \<30 ml/min / 1.73 m2, Or patients with liver insufficiency OR liver failure (Alanine aminotransferase and / or aspartate aminotransferase increased 2.5 times above the upper limit of normal);
4. Clinical assessment of a dressing change risk, Including: Heart failure (NYHA stage grade II or above), any one or more of the stroke, myocardial infarction, and unstable angina pectoris diagnosed within three months;
5. Patients who are pregnant or who are currently being treated with sex hormones and glucocorticoids;
6. incurable malignancy;
7. Other reasons make it difficult to change or stop the drug to complete the diagnosis.

Primary outcomes:
measure: Establish a LC-MS/MS assay-specific cut-off point of screening without medication interfering for primary aldosteronism.
timeFrame: At baseline without medication interfering.
measure: Establish a LC-MS/MS assay-specific cut-off point of CCT without medication interfering for primary aldosteronism.
timeFrame: 2 hours after the captopril challenge test without medication interfering.
Secondary outcomes:
measure: Establish a LC-MS/MS assay-specific cut-off point of screening with medication interfering for primary aldosteronism.
timeFrame: At baseline with medication interfering.
measure: compare the different criteria of Captopril Challenge Test for the diagnosis of primary aldosteronism.
timeFrame: 2 hours after the captopril challenge test without medication interfering.
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Qifu Li
state: Chongqing
city: Chongqing
country: China
facility: Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University
Study officials:
affiliation: First Affiliated Hospital of Chongqing Medical University
name: Qifu Li
role: STUDY_CHAIR
References:
citation: Mulatero P, di Cella SM, Monticone S, Schiavone D, Manzo M, Mengozzi G, Rabbia F, Terzolo M, Gomez-Sanchez EP, Gomez-Sanchez CE, Veglio F. 18-hydroxycorticosterone, 18-hydroxycortisol, and 18-oxocortisol in the diagnosis of primary aldosteronism and its subtypes. J Clin Endocrinol Metab. 2012 Mar;97(3):881-9. doi: 10.1210/jc.2011-2384. Epub 2012 Jan 11.
citation: Xu Z, Yang J, Hu J, Song Y, He W, Luo T, Cheng Q, Ma L, Luo R, Fuller PJ, Cai J, Li Q, Yang S; Chongqing Primary Aldosteronism Study (CONPASS) Group. Primary Aldosteronism in Patients in China With Recently Detected Hypertension. J Am Coll Cardiol. 2020 Apr 28;75(16):1913-1922. doi: 10.1016/j.jacc.2020.02.052.
citation: Fuss CT, Brohm K, Kurlbaum M, Hannemann A, Kendl S, Fassnacht M, Deutschbein T, Hahner S, Kroiss M. Confirmatory testing of primary aldosteronism with saline infusion test and LC-MS/MS. Eur J Endocrinol. 2021 Jan;184(1):167-178. doi: 10.1530/EJE-20-0073.
citation: Young WF Jr. Diagnosis and treatment of primary aldosteronism: practical clinical perspectives. J Intern Med. 2019 Feb;285(2):126-148. doi: 10.1111/joim.12831. Epub 2018 Sep 25.
citation: Olsen MH, Angell SY, Asma S, Boutouyrie P, Burger D, Chirinos JA, Damasceno A, Delles C, Gimenez-Roqueplo AP, Hering D, Lopez-Jaramillo P, Martinez F, Perkovic V, Rietzschel ER, Schillaci G, Schutte AE, Scuteri A, Sharman JE, Wachtell K, Wang JG. A call to action and a lifecourse strategy to address the global burden of raised blood pressure on current and future generations: the Lancet Commission on hypertension. Lancet. 2016 Nov 26;388(10060):2665-2712. doi: 10.1016/S0140-6736(16)31134-5. Epub 2016 Sep 23. No abstract available.
citation: Rehan M, Raizman JE, Cavalier E, Don-Wauchope AC, Holmes DT. Laboratory challenges in primary aldosteronism screening and diagnosis. Clin Biochem. 2015 Apr;48(6):377-87. doi: 10.1016/j.clinbiochem.2015.01.003. Epub 2015 Jan 22.