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

Official title

A Randomized Controlled Trial to Evaluate the Effect of Gallium-68 Pentixafor PET-CT on Surgical Outcomes in Patients With Primary Aldosteronism (The PETAL Trial)

Overview

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.

Interventions

• Diagnostic test 68Ga-pentixafor PET/CT
  Diagnostic PET/CT imaging using gallium-68 labeled pentixafor to assess adrenal CXCR4 expression in patients with primary aldosteronism. The imaging is performed prior to treatment allocation and used to assist lateralization of aldosterone production when combined with adrenal venous sampling (AVS).

Primary outcome measures

• Biochemical remission rate after adrenalectomy (surgery group only) [Time frame: 6 months after adrenalectomy]

Secondary outcome measures (12)

• Clinical remission rate after adrenalectomy or initiation of medical therapy [Time frame: 6 months after treatment (surgery or medication)]
• Agreement rate between PET/CT imaging and adrenal venous sampling (AVS) [Time frame: 6 months after treatment (surgery or medication)]
• Concordance between AVS-based lateralization and immunohistochemical (IHC) expression of CXCR4 and CYP11B2 [Time frame: 6 months after treatment]
• Concordance between PET/CT-based lateralization and immunohistochemical (IHC) expression of CXCR4 and CYP11B2 [Time frame: 6 months after treatment]
• Correlation between the AVS-derived lateralization index and the SUVmax ratio on PET/CT [Time frame: 6 months after treatment]
• Change in plasma aldosterone concentration/aldosterone-to-renin ratio (ARR) [Time frame: Baseline and 6 months after treatment]
• Rate of blood pressure normalization [Time frame: 6 months after treatment]
• Change in antihypertensive medication use [Time frame: Baseline and 6 months after treatment]
• Change in serum potassium level [Time frame: Baseline and 6 months after treatment]
• Frequency and percentage of histologic subtype classification in resected adrenal tissue [Time frame: 3 months after adrenalectomy]
• Size of resected adrenal tumors [Time frame: 3 months after adrenalectomy]
• Correlation between somatic mutations and PET/CT SUVmax ratio [Time frame: 3 months after adrenalecotmy]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

South Korea · 2 centers

• Samsung Medical Center — Seoul
• Seoul National University Hospital — Seoul

Publications

• Kim JH, Ahn CH, Kim SJ, Lee KE, Kim JW, Yoon HK, Lee YM, Sung TY, Kim SW, Shin CS, Koh JM, Lee SH. Outcome-Based Decision-Making Algorithm for Treating Patients with Primary Aldosteronism. Endocrinol Metab (Seoul). 2022 Apr;37(2):369-382. doi: 10.3803/EnM.2022.1391. Epub 2022 Apr 14. PMID 35417953
• Ren X, Cheng G, Wang Z. Advances in the molecular imaging of primary aldosteronism. Ann Nucl Med. 2023 Aug;37(8):433-441. doi: 10.1007/s12149-023-01851-y. Epub 2023 Jul 2. PMID 37393373
• Soinio M, Luukkonen AK, Seppanen M, Kemppainen J, Seppanen J, Pienimaki JP, Leijon H, Vesterinen T, Arola J, Lantto E, Helin S, Tikkanen I, Metso S, Mirtti T, Heiskanen I, Norvio L, Tiikkainen M, Tikkanen T, Sane T, Valimaki M, Gomez-Sanchez CE, Porsti I, Nuutila P, Nevalainen PI, Matikainen N. Functional imaging with 11C-metomidate PET for subtype diagnosis in primary aldosteronism. Eur J Endocri PMID 33055298
• Burton TJ, Mackenzie IS, Balan K, Koo B, Bird N, Soloviev DV, Azizan EA, Aigbirhio F, Gurnell M, Brown MJ. Evaluation of the sensitivity and specificity of (11)C-metomidate positron emission tomography (PET)-CT for lateralizing aldosterone secretion by Conn's adenomas. J Clin Endocrinol Metab. 2012 Jan;97(1):100-9. doi: 10.1210/jc.2011-1537. Epub 2011 Nov 23. PMID 22112805
• Heinze B, Fuss CT, Mulatero P, Beuschlein F, Reincke M, Mustafa M, Schirbel A, Deutschbein T, Williams TA, Rhayem Y, Quinkler M, Rayes N, Monticone S, Wild V, Gomez-Sanchez CE, Reis AC, Petersenn S, Wester HJ, Kropf S, Fassnacht M, Lang K, Herrmann K, Buck AK, Bluemel C, Hahner S. Targeting CXCR4 (CXC Chemokine Receptor Type 4) for Molecular Imaging of Aldosterone-Producing Adenoma. Hypertension. PMID 29279316
• Umakoshi H, Naruse M, Wada N, Ichijo T, Kamemura K, Matsuda Y, Fujii Y, Kai T, Fukuoka T, Sakamoto R, Ogo A, Suzuki T, Nanba K, Tsuiki M; WAVES-J Study Group. Adrenal Venous Sampling in Patients With Positive Screening but Negative Confirmatory Testing for Primary Aldosteronism. Hypertension. 2016 May;67(5):1014-9. doi: 10.1161/HYPERTENSIONAHA.115.06607. Epub 2016 Mar 14. PMID 26975712
• Rossi GP, Auchus RJ, Brown M, Lenders JW, Naruse M, Plouin PF, Satoh F, Young WF Jr. An expert consensus statement on use of adrenal vein sampling for the subtyping of primary aldosteronism. Hypertension. 2014 Jan;63(1):151-60. doi: 10.1161/HYPERTENSIONAHA.113.02097. Epub 2013 Nov 11. PMID 24218436
• Hannemann A, Wallaschofski H. Prevalence of primary aldosteronism in patient's cohorts and in population-based studies--a review of the current literature. Horm Metab Res. 2012 Mar;44(3):157-62. doi: 10.1055/s-0031-1295438. Epub 2011 Dec 1. PMID 22135219

Identifiers

NCT: NCT07027254 · 2502-040-1612

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗