Corticotropin Stimulation in Adrenal Venous Sampling for Patients With Primary Aldosteronism(ADOPA)

Primary Aldosteronism Clinical Trial

Official title:

Corticotropin Stimulation in Adrenal Venous Sampling for Patients With Primary Aldosteronism The ADOPA Randomized Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04461535
• Other study ID #: ADOPA study
• Status: Completed
• Phase: N/A
• Start date: July 8, 2020
• Est. completion date: February 20, 2023

Study information

• Verified date: December 2023
• Source: Chongqing Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 228
• Est. completion date: February 20, 2023
• Est. primary completion date: February 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hyperaldosteronism
• Primary Aldosteronism

Intervention

Drug:
• Adrenocorticotropic hormone
Patients divided into Intervention group need to undergo stimulation with a continuous cosyntropin infusion (50 µg/h started 30 minutes before sampling during AVS). Right and left adrenal venous blood and corresponding peripheral venous blood should be sampled sequentially.

Locations

Country	Name	City	State
China	The First Affilated Hospital of Chongqing Medical University	Chongqing	Chongqing

Sponsors (1)

Lead Sponsor	Collaborator
Chongqing Medical University

Country where clinical trial is conducted

China, 

References & Publications (6)

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. — View Citation

Deinum J, Groenewoud H, van der Wilt GJ, Lenzini L, Rossi GP. Adrenal venous sampling: cosyntropin stimulation or not? Eur J Endocrinol. 2019 Sep;181(3):D15-D26. doi: 10.1530/EJE-18-0844. — View Citation

Dekkers T, Prejbisz A, Kool LJS, Groenewoud HJMM, Velema M, Spiering W, Kolodziejczyk-Kruk S, Arntz M, Kadziela J, Langenhuijsen JF, Kerstens MN, van den Meiracker AH, van den Born BJ, Sweep FCGJ, Hermus ARMM, Januszewicz A, Ligthart-Naber AF, Makai P, va — View Citation

Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, Stowasser M, Young WF Jr. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016 Ma — View 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. E — View 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-Sanch — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Compare the proportion of surgically treated patients with complete biochemical remission in the overall cohort between two groups	Blood was drawn to measure aldosterone, renin and potassium.According to PASO criteria, outcomes of adrenalectomy for unilateral primary aldosteronism were classified into complete, partial, and absent success, for both clinical and biochemical outcomes.The proportion of complete biochemical remission according to PASO consensus criteria.	At 12 months of follow-up.
Secondary	Compare the proportion of surgically treated patients who achieved complete clinical remission in the overall cohort between two groups	The proportion of complete clinical remission according to PASO consensus criteria.Clinical outcomes were determined by the blood pressure response to treatment and the number and dosage of antihypertensive medications.	At 12 months of follow-up.
Secondary	Daily defined doses (DDD) of antihypertensive agents (including MRA), blood pressure, proportion of patients reaching target blood pressure	Daily defined doses (DDD) of antihypertensive agents (including MRA), blood pressure, proportion of patients reaching target blood pressure in each group irrespective of their treatment after 12 months of follow-up	At 12 months of follow-up.
Secondary	Rate of bilaterally successful AVS	Calculate the rate of bilateral successful catheterization.Successful catheterization was defined as SI=2 without ACTH stimulation or SI=3 with ACTH stimulation.	At baseline.
Secondary	Adverse events	Record the occurrence of adverse events, including adrenal venous hemorrhage and related adrenal insufficiency, hypertensive urgencies, anaphylactic shock, venous thrombosis, pulmonary embolism, ect.	At baseline and 12 month of follow-up.