PETAL Trial: Impact of Gallium-68 Pentixafor PET-CT on Surgical Outcomes in Primary Aldosteronism

Not Applicable

Recruiting

• Conditions: Primary Aldosteronism; Secondary Hypertension; Aldosterone-Producing Adenoma; Idiopathic Hyperaldosteronism; Adrenalectomy

• Registration Number: NCT07027254
• Lead Sponsor: Seoul National University Hospital

Brief Summary

This study is a randomized controlled trial to assess the clinical utility of gallium-68 pentixafor PET/CT in the management of primary aldosteronism (PA). We aim to evaluate whether the addition of 68Ga-pentixafor PET/CT to standard adrenal venous sampling (AVS) improves surgical outcomes in patients with unilateral PA.

Detailed Description

Primary aldosteronism (PA) is a common cause of secondary hypertension. Accurate subtype classification (unilateral vs. bilateral) is essential to determine whether patients should receive adrenalectomy or medical therapy. AVS is the current gold standard but has limitations, including its invasiveness, technical difficulty, and risk of failure. Recently, non-invasive imaging techniques such as 68Ga-pentixafor PET/CT and 11C-metomidate PET/CT have emerged as promising alternatives for subtype classification. These PET-based methods target molecular markers (e.g., CXCR4, CYP11B2) and show moderate to high concordance rates with AVS (66.7%-90% for pentixafor). However, there is insufficient prospective evidence on whether these modalities can improve treatment outcomes. This randomized controlled trial aims to assess whether adding 68Ga-pentixafor PET/CT to standard AVS improves surgical outcomes in patients with unilateral PA. Participants are randomized 1:1 to undergo either AVS alone or AVS plus 68Ga-pentixafor PET/CT. Additionally, 11C-metomidate PET/CT is performed in the intervention arm purely for research purposes and will not influence treatment decisions. By improving the precision of subtype classification, this study aims to improve patient selection for adrenalectomy, and ultimately enhance clinical outcomes in primary aldosteronism.

Study Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-06-04
• Study First Submitted QC: 2025-06-16
• Last Update Submitted: 2025-06-16
• Study First Posted: 2025-06-18
• Last Update Posted: 2025-06-18
• Study Start: 2025-06-25
• Primary Completion: 2027-06-01
• Study Completion: 2027-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

• Age ≥19 years
• Diagnosed with PA per 2016 Endocrine Society guidelines
• Underwent adrenal CT
• Signed informed consent

Exclusion Criteria

• Women who are pregnant, breastfeeding, or may become pregnant
• Individuals who refuse to undergo surgery
• Individuals for whom 68Ga-Pentixafor PET/CT, 11C-Metomidate PET/CT, or adrenal venous sampling (AVS) is not feasible or is refused due to underlying conditions
• Individuals who refuse or experience adverse effects from dexamethasone premedication required for 11C-Metomidate PET/CT
• Individuals with a history of abdominal open surgery or retroperitoneal surgery on the same side as the planned adrenalectomy
• Any individual deemed unsuitable for the study at the discretion of the investigator

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Biochemical remission rate after adrenalectomy (surgery group only)	6 months after adrenalectomy	Number of participants achieving biochemical success as defined by PASO criteria will be assessed. Biochemical success is defined as normalization or improvement in aldosterone-to-renin ratio (ARR) and correction of hypokalemia without potassium supplementation in patients with unilateral primary aldosteronism who underwent adrenalectomy.

Secondary Outcome Measures

Name	Time	Method
Correlation between the AVS-derived lateralization index and the SUVmax ratio on PET/CT	6 months after treatment	The correlation between the AVS-derived lateralization index and the SUVmax ratio on PET/CT will be evaluated. SUVmax ratios will be quantitatively compared with AVS findings, including the lateralization index, as well as tumor size and the side of dominant hormone secretion
Change in plasma aldosterone concentration/aldosterone-to-renin ratio (ARR)	Baseline and 6 months after treatment	Change from baseline in plasma aldosterone concentration and ARR will be assessed. Plasma aldosterone and ARR will be measured at baseline and 6 months post-treatment to evaluate endocrine improvement.
Rate of blood pressure normalization	6 months after treatment	Proportion of participants with blood pressure below 140/90 mmHg without escalation of antihypertensive medications will be assessed. Participants achieving target blood pressure without medication escalation will be recorded.
Change in antihypertensive medication use	Baseline and 6 months after treatment	Change in number and dose of antihypertensive medications from baseline will be assessed. Total daily defined dose and number of medications will be compared between baseline and 6 months after treatment.
Change in serum potassium level	Baseline and 6 months after treatment	Change in serum potassium concentration from baseline will be assessed. Serum potassium levels at baseline and 6 months post-treatment will be compared to evaluate metabolic improvement.
Frequency and percentage of histologic subtype classification in resected adrenal tissue	3 months after adrenalectomy	Frequency and percentage of histologic subtype classification in resected adrenal tissue will be assessed. Resected adrenal tissues will be classified according to histologic subtypes, and the distribution of each subtype will be recorded.
Size of resected adrenal tumors	3 months after adrenalectomy	Size of resected adrenal tumors will be assessed. Tumor diameter will be measured in centimeters based on pathology reports.
Correlation between somatic mutations and PET/CT SUVmax ratio	3 months after adrenalecotmy	The correlation between somatic mutations and PET/CT SUVmax ratios of adrenal tumors will be evaluated. Mutation profiles (e.g., KCNJ5, CACNA1D, etc.) will be analyzed in relation to SUVmax measurements obtained from PET/CT imaging.
Clinical remission rate after adrenalectomy or initiation of medical therapy	6 months after treatment (surgery or medication)	Number of participants achieving clinical success according to PASO (surgical group) or PAMO (medical group) criteria will be assessed. Clinical success includes normalization of blood pressure and reduction in number or dose of antihypertensive medications after surgery or medical therapy.
Agreement rate between PET/CT imaging and adrenal venous sampling (AVS)	6 months after treatment (surgery or medication)	Agreement rate between 68Ga-pentixafor PET/CT (+11C-metomidate PET/CT for subgroup) and adrenal venous sampling (AVS) will be assessed. Diagnostic agreement will be evaluated based on lateralization patterns from PET/CT and AVS using predefined laterality thresholds.
Concordance between AVS-based lateralization and immunohistochemical (IHC) expression of CXCR4 and CYP11B2	6 months after treatment	Concordance between AVS-based lateralization and immunohistochemical (IHC) expression of CXCR4 and CYP11B2 will be assessed. IHC positivity for CXCR4 and CYP11B2 will be recorded as presence or absence in each adrenal lesion. Concordance will be evaluated by comparing lateralization results from AVS with the presence or absence of expression.
Concordance between PET/CT-based lateralization and immunohistochemical (IHC) expression of CXCR4 and CYP11B2	6 months after treatment	Concordance between PET/CT-based lateralization and immunohistochemical (IHC) expression of CXCR4 and CYP11B2 will be assessed. IHC positivity for CXCR4 and CYP11B2 will be recorded as presence or absence in each adrenal lesion. Concordance will be evaluated by comparing PET/CT-based lateralization with the presence or absence of expression in the corresponding adrenal tissue.

Trial Locations

Locations (2)

Samsung Medical Center; 🇰🇷 Seoul, Gangnam-gu, Korea, Republic of

Seoul National University Hospital; 🇰🇷 Seoul, Jongno-gu, Korea, Republic of