GALLIUM (68GA), PENTIXAFOR for Primary aldosteronism

Inclusion criteria

• {"criterion_text":"- The patient has a diagnosis of primary aldosteronism, confirmed by elevated aldosterone/renin ratio (ARR) and intravenous salt-loading test (according to the Endocrine Society guidelines)"}
• {"criterion_text":"- Patients who fall in the “grey area” according to the Endocrine Society guidelines (1), will be discussed with all site investigators before inclusion to reach consensus on the diagnosis before inclusion."}
• {"criterion_text":"- Age over 18 years at time of consent"}
• {"criterion_text":"- Signed informed consent"}

Exclusion criteria

• {"criterion_text":"- Refusal by the patients to undergo AVS, [68Ga]Ga-PentixaFor PET/CT, CT, or adrenalectomy"}
• {"criterion_text":"- Suspicion of familial hyperaldosteronism type 1 (FH-1), type 2 (FH-2), type 3 (FH-3), or type 4 (FH-4)"}
• {"criterion_text":"- Suspicion of adrenocortical carcinoma"}
• {"criterion_text":"- Severe comorbidity potentially interfering with treatment or health-related quality of life"}
• {"criterion_text":"- Requirement of medication interfering with the study protocol"}
• {"criterion_text":"- Any medical condition present that in the opinion of the investigator will affect patients’ clinical status."}
• {"criterion_text":"- Pregnancy or lactation"}
• {"criterion_text":"- Estimated glomerular filtration rate (eGFR) < 40 ml/min/1.73m²"}

Primary endpoints

• {"endpoint_text":"- To assess the concordance between [68Ga]Ga-PentixaFor PET/CT and AVS for identification and/or lateralization of APAs in patients with PA. (Step 1)","definition_or_measurement_approach":"Concordance measured by comparison of PET/CT imaging results with AVS for identification/lateralization of aldosterone-producing adenomas (APAs)."}
• {"endpoint_text":"- To assess non-inferiority in terms of clinical outcomes of [68Ga]Ga-PentixaFor PET/CT imaging vs. AVS in subtyping of patients with PA randomized to either [68Ga]Ga-PentixaFor PET/CT imaging or AVS confirmed by the surrogate Standard of Truth (SoT) daily defined doses (DDD) in patients after 6 months follow-up. (Step 2)","definition_or_measurement_approach":"Non-inferiority assessed on clinical outcomes using surrogate Standard of Truth (SoT) daily defined doses (DDD) with assessment at 6 months follow-up."}

Secondary endpoints

• {"endpoint_text":"- To establish definitive quantitative criteria of [68Ga]Ga-PentixaFor uptake in unilateral and bilateral PA for SUVs, liver-to-lesion ratio and lesion-to-contralateral ratio. (step 1)","definition_or_measurement_approach":"Quantitative PET uptake metrics including SUV measures, liver-to-lesion ratio and lesion-to-contralateral ratio."}
• {"endpoint_text":"- In patients who receive unilateral adrenalectomy, compare quantitative data in PET/CT imaging between immunohistochemically (CYP11B2 and CXCR4 staining) diagnosed multinodular hyperplasia and solitary adenomas. (step 1)","definition_or_measurement_approach":"Comparison of PET/CT quantitative metrics with immunohistochemical diagnosis (CYP11B2 and CXCR4 staining) of surgical specimens."}
• {"endpoint_text":"- To assess biochemical and clinical outcomes based on PASO criteria (step 1)","definition_or_measurement_approach":"Biochemical and clinical outcomes assessed using PASO criteria after treatment (step 1)."}
• {"endpoint_text":"- To asses biochemical and clinical outcomes after adrenalectomy of [68Ga]Ga-PentixaFor PET/CT imaging vs AVS in subtyping patients with PA by using the PASO criteria for clinical and biochemical outcome measures (complete, partial or absent). (step2)","definition_or_measurement_approach":"Clinical and biochemical outcomes post-adrenalectomy categorized by PASO criteria (complete/partial/absent)."}
• {"endpoint_text":"- To evaluate reproducibility of [68Ga]Ga-PentixaFor PET/CT by comparison of two [68Ga]Ga-PentixaFor PET/CT scans with an interval of 1-14 days in the first 10 patients undergoing [68Ga]Ga-PentixaFor PET/CT. (step 2)","definition_or_measurement_approach":"Reproducibility assessed by repeat PET/CT scans 1–14 days apart in first 10 patients and comparing quantitative measures."}
• {"endpoint_text":"- To assess intra- and inter-reader agreement of [68Ga]Ga-PentixaFor PET/CT for subtyping for each imaging center (step 2)","definition_or_measurement_approach":"Assessment of intra- and inter-reader agreement (e.g., kappa or ICC) for PET/CT subtyping per center."}
• {"endpoint_text":"- To analyze inter-observer agreement of [68Ga]Ga-PentixaFor PET/CT between the imaging centers in terms of subtyping. (step 2)","definition_or_measurement_approach":"Inter-observer agreement analyses across imaging centers for subtyping decisions."}
• {"endpoint_text":"- In patients who receive unilateral adrenalectomy, compare quantitative data in PET/CT imaging between immunohistochemically (CYP11B2 and CXCR4 staining) diagnosed multinodular hyperplasia and solitary adenomas. (step 2)","definition_or_measurement_approach":"As in step 1, comparison of PET metrics with immunohistochemical classification of resected tissue."}
• {"endpoint_text":"- To perform cost effectiveness analysis of AVS versus [68Ga]Ga-PentixaFor PET/CT management. (step 2)","definition_or_measurement_approach":"Cost-effectiveness analysis comparing AVS and PET/CT management strategies (health economic evaluation)."}
• {"endpoint_text":"- To evaluate quality of life as assessed by EQ-5D-5L questionnaire and the Short Form health survey (SF36) of [68Ga]Ga-PentixaFor PET/CT versus AVS management. (step 2)","definition_or_measurement_approach":"Quality of life measured using EQ-5D-5L and SF-36 questionnaires."}
• {"endpoint_text":"- Determination of the rate of inconclusive results and/or failure of subtype diagnosis by [68Ga]Ga-PentixaFor PET/CT imaging or AVS. (step 2)","definition_or_measurement_approach":"Rate of inconclusive or failed subtype diagnoses for each method."}
• {"endpoint_text":"- To assess safety and intolerability. (step 2)","definition_or_measurement_approach":"Safety assessed by recording adverse events and intolerability of procedures/imaging."}
• {"endpoint_text":"- To assess image quality of [68Ga]Ga-PentixaFor PET/CT imaging, using the SUVmean, SUVmax, and SUVpeak, lesion-to-liver ratio, contrast-to-noise ratio, and signal-to-noise ratio. (step 2)","definition_or_measurement_approach":"Image quality metrics include SUVmean/SUVmax/SUVpeak, lesion-to-liver ratio, contrast-to-noise and signal-to-noise ratios."}
• {"endpoint_text":"- To assess biochemical and clinical outcomes in patients treated with antihypertensive drugs based on [68Ga]Ga-PentixaFor PET/CT imaging vs AVS in subtyping PA by using the PAMO criteria for clinical and biochemical outcome measures (complete, partial or absent) (currently unpublished data).","definition_or_measurement_approach":"Clinical and biochemical outcomes in patients managed medically assessed using PAMO criteria."}

Netherlands

Earliest CTIS Part Ii Submission Date

15-07-2024

Latest Decision Or Authorization Date

26-02-2025

Processing Time Days

226

Number Of Sites

5

Number Of Participants

228

Primary sponsor

Full Name

Stichting Radboud universitair medisch centrum

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands