Clinical trial NCT04461535: Corticotropin Stimulation in Adrenal Venous Sampling for Patients With Primary Aldosteronism(ADOPA)
Official title: Corticotropin Stimulation in Adrenal Venous Sampling for Patients With Primary Aldosteronism The ADOPA Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Primary Aldosteronism
Keywords: primary aldosteronism
adrenal venous sampling
adrenocorticotropic hormone
Lead sponsor: Chongqing Medical University
Sponsor class: OTHER
First posted: 2020-07-08
Enrollment: 228
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: To compare the effect of different procedures of AVS(with or without ACTH stimulation) on the long-term outcomes of patients with PA

Detailed description: This is a prospective and randomized study involving patients with primary aldosteronism(PA) who completed AVS.

All paticipants will be randomized into ACTH-stimulated group(Intervention group) and ACTH-unstimulated group(Control group) Cannulation was considered successful when the selectivity index (SI), namely plasma cortisol concentration (PCC) in adrenal vein/PCC in IVC≥3 with ACTH stimulation or SI≥2 without ACTH stimulation. The ratio of PAC: PCC on the side with the higher ratio over the contralateral PAC: PCC ratio is defined as the lateralization index (LI). Lateralization of aldosterone excess was defined as LI≥4 irrespective of ACTH use. Patients with LI between 2 and 4 together with contralateral suppression (PAC/PCC of non-dominant side \< PAC/PCC of IVC) or CT showing a typical adenoma on the dominant side were also considered to have lateralized disease. Patients with LI \< 2 or LI 2-4 without meeting the above criteria were diagnosed as BPA.

In case of technical AVS failure or bilateral PAC/PCC in adrenal venous blood lower than peripheral blood, if the patient meets one of the following criteria, adrenalectomy was recommended: 1) unilateral nodule on CT (≥ 1 cm), no observable nodules or hyperplasia on contralateral adrenal, and PAC ≥ 20 ng/dl, PRC \< 5 μIU/ml, K ≤ 3.5mmol/l; 2) unilateral nodule on CT (≥ 1 cm), no observable nodules or hyperplasia on contralateral adrenal, and the contralateral index≤0.5 in AVS.

Surgical intervention is recommended for unilateral PA (UPA) whereas bilateral PA (BPA) is typically treated with oral mineralocorticoid receptor antagonists such as spironolactone. The aim is to compare the long-term outcomes of patients with PA.

To evaluate whether the treatment decision (surgical or medical treatment) based on different AVS procedures (with or without ACTH stimulation) would lead to different outcomes in patients with PA.

Eligibility criteria: 1.Inclusion criteria: Patients who meet the following criterion can be included in this study.

1. Aged between 18-70, male or female, with legal capacity
2. PA diagnosis confirmed by at least one confirmatory test: positive PA screening (ARR≥ 2.0 ng·dl-1/IU·l-1) and at least one positive PA confirmatory test (PAC-post CCT ≥11 ng/dl, PAC-post SSIT≥8·0 ng/dl, or if confirmatory tests were in grey zone (i.e, PAC 8-11 ng/ml two hours after administration of 50 mg captopril or PAC 60-80 pg/ml after the infusion of 2L normal saline), PAC-post FST≥6·0 ng/dl);

2.Exclusion criteria: Patients with one of the following conditions will be excluded in this study:

1. refusal by the patient to undergo AVS or adrenalectomy;
2. meeting the criteria for bypassing AVS \[i.e. younger than 35 years old, with typical aldosterone-producing adenomas characteristics (plasma aldosterone \>30ng/dl, serum potassium \<3·5mmol/l, CT indicated unilateral 1cm low-density adenoma) ;
3. allergic to ACTH or contrast media;
4. pregnant or lactating women;
5. patients with a history of uncontrolled malignant tumor;
6. complicated with Cushing's syndrome \[including subclinical Cushing: cortisol after 1mg dexamethasone suppression test (DST)\>138 nmol/l or cortisol after 1mg DST 50-138 nmol/l plus adrenocorticotrophic hormone (ACTH)\<10pg/ml;
7. diagnosed with familial hyperaldosteronism;
8. with imaging characteristics suggestive of pheochromocytoma or adrenal cortical carcinoma;
9. patients unsuitable for surgery, such as those with heart failure (New York Heart Association (NYHA) class III or IV), severe anemia (Hemoglobin\<60g/L), stroke or acute coronary syndrome within 3 months, severe ascites and cirrhosis, estimated glomerulus filtration rate\<30ml/min/m2;
10. with alcohol or drug abuse and active mental health disorders.

Primary outcomes:
measure: Compare the proportion of surgically treated patients with complete biochemical remission in the overall cohort between two groups
timeFrame: At 12 months of follow-up.
Secondary outcomes:
measure: Compare the proportion of surgically treated patients who achieved complete clinical remission in the overall cohort between two groups
timeFrame: At 12 months of follow-up.
measure: Daily defined doses (DDD) of antihypertensive agents (including MRA), blood pressure, proportion of patients reaching target blood pressure
timeFrame: At 12 months of follow-up.
measure: Rate of bilaterally successful AVS
timeFrame: At baseline.
measure: Adverse events
timeFrame: At baseline and 12 month of follow-up.
Other outcomes:
Locations:
city: Chongqing
country: China
facility: The First Affilated Hospital of Chongqing Medical University
state: Chongqing
Study officials:
affiliation: the Chongqing Primary Aldosteronism Study (CONPASS) Group
name: Qifu Li, PhD
role: STUDY_CHAIR
References:
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citation: Nishikawa T, Omura M, Satoh F, Shibata H, Takahashi K, Tamura N, Tanabe A; Task Force Committee on Primary Aldosteronism, The Japan Endocrine Society. Guidelines for the diagnosis and treatment of primary aldosteronism--the Japan Endocrine Society 2009. Endocr J. 2011;58(9):711-21. doi: 10.1507/endocrj.ej11-0133. Epub 2011 Aug 9.
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citation: Buffolo F, Monticone S, Williams TA, Rossato D, Burrello J, Tetti M, Veglio F, Mulatero P. Subtype Diagnosis of Primary Aldosteronism: Is Adrenal Vein Sampling Always Necessary? Int J Mol Sci. 2017 Apr 17;18(4):848. doi: 10.3390/ijms18040848.
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citation: Williams TA, Lenders JWM, Mulatero P, Burrello J, Rottenkolber M, Adolf C, Satoh F, Amar L, Quinkler M, Deinum J, Beuschlein F, Kitamoto KK, Pham U, Morimoto R, Umakoshi H, Prejbisz A, Kocjan T, Naruse M, Stowasser M, Nishikawa T, Young WF Jr, Gomez-Sanchez CE, Funder JW, Reincke M; Primary Aldosteronism Surgery Outcome (PASO) investigators. Outcomes after adrenalectomy for unilateral primary aldosteronism: an international consensus on outcome measures and analysis of remission rates in an international cohort. Lancet Diabetes Endocrinol. 2017 Sep;5(9):689-699. doi: 10.1016/S2213-8587(17)30135-3. Epub 2017 May 30.