Metarapone: Metirapone is an inhibitor of the enzyme 11-β-adrenal hydroxylase, which is deputed to catalyze the conversion of 11-desoxycortisol (11-S) to cortisol and 11-deoxycorticosterone (DOC) to corticosterone.
Standardized antihypertensive therapy: Standardized antihypertensive therapy, as provided in the normal course of care and in accordance with current European guidelines.
Study summary
Drug interventional, controlled, randomized open-label, parallel-group, multicenter study in patients with bilateral adrenal incidentalomas associated with subclinical Cushing's syndrome
Eligibility
Sex
ALL
Min age
18 Years
Max age
75 Years
Healthy volunteers
No
Inclusion Criteria:
Inclusion criteria - run-in (phase 1)
* Unilateral or bilateral adrenal nodules with benign features associated with thickening of the adrenal arms \>5 mm on abdominal CT scan
* SCS (detected 2 times in the 6 months before run-in) defined by the absence of catabolic signs of Cushing's syndrome in association with any of these 3 conditions:
* Cortisol levels after dexamethasone 1 mg test \>50 nmol/L associated with baseline ACTH \<10 pg/mL
* Cortisol levels after dexamethasone 1 mg test \>50 nmol/L associated with increased nocturnal (11 pm) salivary cortisol
* Cortisol levels after dexamethasone 1 mg test \>138 nmol/L
* Hypertension (BP ≥140/90 mmHg and/or ongoing antihypertensive treatment)
* Patients who cannot undergo surgery
* Acquisition of informed consent.
Inclusion criteria - randomization (phase 2)
\- BP \>100/60 mmHg and \<130/85 mmHg on antihypertensive therapy (lowest effective dose) within 6-10 months after enrollment.
Exclusion Criteria:
* Body mass index ≥40 kg/m2
* Pregnant or lactating women; diagnosis of pregnancy will be made by serum β-HCG assay
* Women of childbearing age using contraceptive measures other than barrier contraception. Barrier contraceptive measures are: o Male or female condom with or without spermicide o Cervical cup, diaphragm or sponges with spermicide o Combination of male condom and cervical cup, diaphragm or sponges with spermicide (dual barrier methods)
* Treatment with steroids in the last year before enrollment
* Taking medications known to interfere with Metirapone
* Known or suspected hypersensitivity to the drug or drug class under study
* Patients with serious clinical conditions that, in the opinion of the Investigator, contraindicate the patient's participation in the study
* Patients with primary corticosurrenal insufficiency, impaired adrenal secretion, and severe hypopituitarism
* Patients with impaired liver function
* Patients with untreated hypothyroidism or being treated with drugs that have an action on the hypothalamic-pituitary-adrenal axis
* Patients with hypersensitivity to the active ingredient or any of the excipients listed in section 6.1 of the RCP - Metirapone.
Primary outcome measure(s)
Change in Number and/or Dosage of Antihypertensive Drugs at 12 Months with Metirapone Treatment, Maintaining Target Blood Pressure Range — through study completion, an average of 2 months This measure will assess any change in the number or dosage of antihypertensive medications required after 12 months of treatment with Metirapone, while maintaining the target blood pressure range (BP \>100/60 mmHg and \<130/85 mmHg).
Trial sites (3)
Facility
City
Region
Status
IRCCS Azienda Ospedaliero-Universitaria di Bologna
Bologna
Italy
Recruiting
Azienda Ospedaliera Universitaria Federico II
Naples
Italy
Recruiting
Azienda Ospedale-Università Padova
Padova
Italy
Recruiting
More IRCCS Azienda Ospedaliero-Universitaria di Bologna trials in Italy
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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