CXCR4-directed [68Ga]Ga-PentixaFor PET/CT versus adrenal vein sampling performance: a study protocol for a randomised two-step controlled diagnoStic Trial Ultimately comparing hypertenSion outcome in primary aldosteronism (CASTUS)

Abstract

Introduction: Primary aldosteronism (PA) is the most common form of secondary hypertension. It is caused by overproduction of aldosterone by either a unilateral aldosterone-producing adenoma (APA) or by bilateral adrenal hyperplasia (BAH). Distinction is crucial, because PA is cured by adrenalectomy in APA and is treated by mineralocorticoid receptor antagonists in BAH. The distinction is currently made by adrenal vein sampling (AVS). AVS is a costly, invasive and complex technical procedure with limited availability and is not superior in terms of outcomes to CT scan-based diagnosis. Thus, there is a need for a cheaper, non-invasive and readily available diagnostic tool in PA. We propose a new diagnostic imaging modality employing the positron emission tomography (PET) tracer [68Ga]Ga-PentixaFor. This tracer has high focal uptake in APAs, whereas low uptake was shown in patients with normal adrenals. Thus, [68Ga]Ga-PentixaFor PET/CT is an imaging modality with the potential to improve subtyping of PA. It is readily available, safe and, as an out-patient procedure, much cheaper diagnostic method than AVS.

Methods and analysis: We present a two-step randomised controlled trial (RCT) protocol in which we assess the accuracy of [68Ga]Ga-PentixaFor PET/CT in the first step and compare [68Ga]Ga-PentixaFor PET/CT to AVS in the second step. In the first step, the concordance will be determined between [68Ga]Ga-PentixaFor PET/CT and AVS and a concordance probability is calculated with a Bayesian prediction model. In the second step, we will compare [68Ga]Ga-PentixaFor PET/CT and AVS for clinical outcome and intensity of hypertensive drug use defined as daily defined doses in a RCT.

Ethics and dissemination: Ethics approval was acquired from the medical ethical committee East-Netherlands (METC Oost-Nederland). Results will be disseminated through peer-reviewed articles.

Trial registration number: NL9625.

Keywords: diagnostic radiology; hypertension; radiology & imaging; vascular medicine.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Randomisation and treatment of patients with PA in the second step. AVS, adrenal vein sampling. PA, primary aldosteronism.

Figure 2

Formulas and cut-offs for selectivity, lateralisation and suppression index in AVS. AVS, adrenal vein sampling.

Figure 3

A flowchart diagram which details step 1 and decision making prior to advancing to step 2. AVS, adrenal vein sampling; RCT, randomised controlled trial.

Figure 4

Pie chart of CT managed diagnosis of PA. Assuming 33% of the CT diagnosed APA is incorrect, CT diagnoses APA in 33.5% and BAH in 66.5% of the PA cases. APA, aldosterone-producing adenoma; BAH, bilateral adrenal hyperplasia; PA, primary aldosteronism.