CXCR4-directed [68Ga]Ga-PentixaFor PET/CT vs AVS performance in a diagnoStic randomized Trial Ultimately comparing hypertenSion outcome in primary aldosteronism

INTERVENTION: Product Name: [68Ga]Ga‐Pentixafor Product Code: 9913 Pharmaceutical Form: Solution for injection/infusion INN or Proposed INN: [68Ga]Ga‐PentixaFor CAS Number: 1345698‐96‐5 Other descriptive name: PENTIXAFOR GALLIUM GA‐68 Concentration unit: MBq megabecquerel(s) Concentration type: range Concentration number: 100‐200 CONDITION: Primary Aldosteronism ; MedDRA version: 20.1 Level: PT Classification code 10036692 Term: Primary hyperaldosteronism System Organ Class: 10014698 ‐ Endocrine disorders Therapeutic area: Diseases [C] ‐ Cardiovascular Diseases [C14] PRIMARY OUTCOME: Main Objective: ‐To assess the concordance between [68Ga]Ga‐PentixaFor PET/CT and AVS for identification and/or lateralization of aldosterone producing adenomas in patients with primary aldosteronism. (Step 1) ; ‐To assess the quantity of antihypertensive medication after 1 year of follow‐up needed to normalize blood pressure in patients who have been managed for primair aldosteronisme according to either AVS or [68Ga]Ga‐PentixaFor PET/CT. (Step 2) ; Primary end point(s): Step 1: Primary end point is a concordance between [68Ga]Ga‐PentixaFor PET/CT and AVS of at least 50%; Step 2: [68Ga]Ga‐PentixaFor PET/CT results in less than 1 daily defined doses compared to AVS. Secondary Objective: ‐ To establish definitive quantitative criteria of [68Ga]Ga‐PentixaFor uptake in unilateral and bilateral PA. (Step 1); ‐ In patients who receive an unilateral adrenalectomy, we compare [68Ga]Ga‐PentixaFor uptake in PET/CT imaging between immunohistochemically (CYP11B2 staining) diagnosed multinodular hyperplasia and solitary adenomas. (Step 1, Step 2); ‐ To assess the diagnostic accuracy of adrenal CT compared with [68Ga]Ga‐PentixaFor PET/CT and AVS. (Step 1, Step 2); ‐ Cost analysis of AVS versus [68Ga]Ga‐PentixaFor PET/CT management. (Step 2); ‐ Changes in quality of life assessed by a validated disease specific health‐related Quality of Life (HRQoL) questionnaire and the Short Form health survey (SF36)(2, 3) (Step 2); ‐ To perform a safety analysis of [68Ga]‐Pentixafor administration on clinical symptoms by Adverse Events outcomes. (Step 2); Timepoint(s) of evaluation of this end point: Step 1: We evaluate the concordance after the [68Ga]Ga‐PentixaFor PET/CT and AVS is performed; Step 2: We will evaluate the daily defined doses after 1 year of follow‐up INCLUSION CRITERIA: ‐ The patient has a diagnosis of primary aldosteronism, confirmed by an elevated aldosterone/rennin ratio (ARR) and an intravenous salt‐loading test (according to the Endocrine Society guidelines)(1) ‐ Age over 18 years at time of consent ‐ Signed informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 281 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 281 SECONDARY OUTCOME: Secondary end point(s): 1. To establish definitive quantitative criteria of [68Ga]Ga‐PentixaFor uptake in unilateral and bilateral PA for with the SUVs, liver‐to‐lesion ratio and lesion‐to‐contralateral ratio. (Step 1); 2. In patients who receive a unilateral adrenalectomy, compare quantitative data in PET/CT imaging between immunohistochemically (CYP11B2 staining) diagnosed multinodular hyperplasia and solitary adenomas. (Step 1, Step 2); 3. Lateralization of the [68Ga]Ga‐PentixaFor PET/CT will be compared with lateralization results of the CT‐scan, which is always made prior to AVS (unilaterally enlarged adrenal with a normal contralateral gland or bilaterally enlarged glands). (Step 1); 4. Cost analysis of AVS versus [68Ga]Ga‐PentixaFor PET/CT management. (Step 2); 5. Quality of life as assessed by a validated disease specific Health‐Related Quality of Life (HRQoL) questionnaire and the Short Form health survey (SF36)(2, 3). (Step 2); 6. To perform a safety analysis of [68Ga]Ga‐PentixaFor administration on clinical symptoms by Adverse Events outcomes. (Step 1) Timepoint(s) of evaluation of this end point: 1. After the lateralization results of AVS of the last included patient is known.; 2. After the pathology results of the last included patient is reported.; 3. After the lateralization results of AVS of the last included patient is known.; 4. After the last included patients has been treated; 5. After 1 year follow‐up; 6. After each adverse event