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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Stichting Radboud universitair medisch centrum

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Investigative Techniques [E05], Diseases [C] - Hormonal diseases [C19]

Trial duration

28 Jan 2025 → ongoing

Decision date (initial)

2024-08-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-512628-12-00

EudraCT number

2021-003460-27

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis

-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)

Conditions and MedDRA coding

Primary aldosteronism

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. 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)
2. 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.
3. Age over 18 years at time of consent
4. Signed informed consent

Exclusion criteria 8

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

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)
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 endpoints 14

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)
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 1)
3. To assess biochemical and clinical outcomes based on PASO criteria (step 1)
4. 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)
5. 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)
6. To assess intra- and inter-reader agreement of [68Ga]Ga-PentixaFor PET/CT for subtyping for each imaging center (step 2)
7. To analyze inter-observer agreement of [68Ga]Ga-PentixaFor PET/CT between the imaging centers in terms of subtyping. (step 2)
8. 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)
9. To perform cost effectiveness analysis of AVS versus [68Ga]Ga-PentixaFor PET/CT management. (step 2)
10. 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)
11. Determination of the rate of inconclusive results and/or failure of subtype diagnosis by [68Ga]Ga-PentixaFor PET/CT imaging or AVS. (step 2)
12. To assess safety and intolerability. (step 2)
13. 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)
14. 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).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Stichting Radboud universitair medisch centrum

Sponsor organisation

Stichting Radboud universitair medisch centrum

Address

Geert Grooteplein Zuid 10

City

Nijmegen

Postcode

6525 GA

Country

Netherlands

Scientific contact point

Organisation

Stichting Radboud universitair medisch centrum

Contact name

J. Deinum

Public contact point

Organisation

Stichting Radboud universitair medisch centrum

Contact name

J.F. Langenhuijsen

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications