CXCR4-directed [68Ga]Ga-PentixaFor PET/CT vs AVS performance in a diagnoStic randomized Trial Ultimately comparing hypertenSion outcome in primary aldosteronism (CASTUS trial)
- Conditions
- Primary aldosteronism
- Registration Number
- 2024-512628-12-00
- Lead Sponsor
- Stichting Radboud universitair medisch centrum
- Brief Summary
-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)
-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)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing, recruiting
- Sex
- Not specified
- Target Recruitment
- 228
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)
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.
Age over 18 years at time of consent
Signed informed consent
Refusal by the patients to undergo AVS, [68Ga]Ga-PentixaFor PET/CT, CT, or adrenalectomy
Suspicion of familial hyperaldosteronism type 1 (FH-1), type 2 (FH-2), type 3 (FH-3), or type 4 (FH-4)
Suspicion of adrenocortical carcinoma
Severe comorbidity potentially interfering with treatment or health-related quality of life
Requirement of medication interfering with the study protocol
Any medical condition present that in the opinion of the investigator will affect patients’ clinical status.
Pregnancy or lactation
Estimated glomerular filtration rate (eGFR) < 40 ml/min/1.73m²
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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) 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)
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) 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)
- Secondary Outcome Measures
Name Time Method 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) 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)
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) 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)
To assess biochemical and clinical outcomes based on PASO criteria (step 1) To assess biochemical and clinical outcomes based on PASO criteria (step 1)
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) 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)
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) 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)
To assess intra- and inter-reader agreement of [68Ga]Ga-PentixaFor PET/CT for subtyping for each imaging center (step 2) To assess intra- and inter-reader agreement of [68Ga]Ga-PentixaFor PET/CT for subtyping for each imaging center (step 2)
To analyze inter-observer agreement of [68Ga]Ga-PentixaFor PET/CT between the imaging centers in terms of subtyping. (step 2) To analyze inter-observer agreement of [68Ga]Ga-PentixaFor PET/CT between the imaging centers in terms of subtyping. (step 2)
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) 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)
To perform cost effectiveness analysis of AVS versus [68Ga]Ga-PentixaFor PET/CT management. (step 2) To perform cost effectiveness analysis of AVS versus [68Ga]Ga-PentixaFor PET/CT management. (step 2)
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) 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)
Determination of the rate of inconclusive results and/or failure of subtype diagnosis by [68Ga]Ga-PentixaFor PET/CT imaging or AVS. (step 2) Determination of the rate of inconclusive results and/or failure of subtype diagnosis by [68Ga]Ga-PentixaFor PET/CT imaging or AVS. (step 2)
To assess safety and intolerability. (step 2) To assess safety and intolerability. (step 2)
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) 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)
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). 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).
Trial Locations
- Locations (5)
Universitair Medisch Centrum Utrecht
🇳🇱Utrecht, Netherlands
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
🇳🇱Rotterdam, Netherlands
Radboud universitair medisch centrum / RADBOUDUMC
🇳🇱Nijmegen, Netherlands
Rijnstate Ziekenhuis Stichting
🇳🇱Arnhem, Netherlands
Isala Klinieken Stichting
🇳🇱Zwolle, Netherlands
Universitair Medisch Centrum Utrecht🇳🇱Utrecht, NetherlandsW. SpieringSite contact+31887556312w.spiering@umcutrecht.nl