Clinical Trials Logo

Clinical Trial Summary

Purpose of this clinical trial is to improve prediction of outcomes from surgical intervention in patients with Primary aldosteronism, and evaluate the merits of non-invasive metomidate PET CT versus adrenal vein sampling in the diagnosis of surgically correctable aldosteronism.


Clinical Trial Description

This is an observational multi-centre prospective cohort study which takes place within secondary and tertiary care. All participants will have the same two investigations performed in random order. These are as follows: 11C- metomidate PET CT This is a one-hour non-invasive study, prior to which participants are treated with dexamethasone for 3 days. A proportion of patients will have an additional 18F-CETO PET CT scan to measure concordance between the two PET CT scans. Adrenal Vein Sampling This is an invasive investigation in which both adrenal veins are cannulated and blood collected for measurement of adrenal steroid hormones. Adrenocorticotrophic hormone (ACTH) is administered prior to AVS in order to ensure steroid hormone secretion during the procedure. The investigators will standardise the start-time of treatment with spironolactone, which is first-choice treatment for participants with primary aldosteronism, in order that the pre-spironolactone blood pressure and biochemistry can be compared with subsequent measurements post-surgery, and the changes during the first month of spironolactone treatment can be used to assess their value in predicting response to surgery. Sub-study of Repeat 11-C Metomidate PET CT before and after Spironolactone therapy In order to determine whether it will be necessary for the start of spironolactone treatment to be delayed in all participants until after both investigations are completed, the investigators will perform a sub-study, early in MATCH, in which 6 patients have their PET CT repeated after at least 6 weeks treatment with spironolactone. (This is the conventional period of time for which spironolactone is withdrawn prior to AVS.) Follow-up management and investigations The investigators anticipate ~50% of participants will be found on one or both investigations to have unilateral PA, and be recommended for adrenalectomy. The primary outcome measurements will be at 6 months after surgery, or 9-12 months following MDT decision, in those who do not undergo surgery. Primary outcomes: The following primary outcomes will be analysed hierarchically, with each analysis being considered as part of the primary analysis if all preceding analyses demonstrate statistical significance at p<0.05. Otherwise, analyses of subsequent outcomes will be considered to be secondary analyses. - Normalisation of ARR at 6 months, defined as - ARRactivity < 750 pmol/L per ng/ml/hr - ARRmass < 91 miU/L - Change in BP (mean of at least 6 measurements from home monitoring, or mean of at least 2 measurements from clinic ) from baseline to 6 months. - Cure of hypertension at 6 months. Definitions of biochemical and clinical success based on the PASO criteria (using on data available on eCRF) will be used. Each primary outcome will be analysed in the subgroup of participants who undergo surgery. For each of the above outcomes, AVS and 11C-metomidate PET CT will be judged to be 'accurate' if it indicated unilateral disease and if normalisation of ARR, reduction in SBP or cure of hypertension (measured hierarchically, in turn) was achieved at 6 months post-surgery; or if it did not indicate unilateral disease and the above outcomes were not achieved. Estimated differences in accuracy will be reported with 95% CI and p-value between 11C-metomidate PET CT and AVS. For cure of hypertension at 6 month, non-inferiority of 11C-metomidate PET CT will be declared if the lower limit of the above 95% CI is greater than -17%. Each measure of cure based on the PASO criteria (biochemical, clinical) will be analysed in turn. Superiority of 11-C metomidate PET CT will be declared if p<0.05 and the lower limit of the 95% CI is greater than 0%." Secondary outcomes The secondary outcomes are: - Biochemical success (based on PASO criteria) at 6 months, analysed as a 3-level categorical variable (complete, partial, absent) - Clinical success (based on PASO criteria) at 6 months, analysed as a 3-level categorical variable (complete, partial, absent) - Change in serum Potassium from baseline to 6 months - Change in ARRactivity or ARRmass from baseline to 6 months - Change in home SBP and DBP from baseline to 6 months - Change in clinic SBP and DBO from baseline to 6 months - Change in blood levels of Troponin, Brain Natriuretic Peptide from baseline to 6 months - Changes in cardiac MRI measures of heart structure, anatomy and blood flow from baseline to 6 months - Change in quality of life measures from baseline to 6 months Secondary (and Primary) outcomes will be compared between participants who underwent surgery and those who did not; for those who underwent surgery, between those for whom surgery was indicated by AVS only, 11C-metomidate PET CT only, or for both investigations. The sample size calculation has been performed to permit detection of a significant influence on outcome where the smallest number of patients will be available. This is the group of patients in whom the two diagnostic techniques give discordant results, estimated to be ~20% of the total. Recruitment of 140 patients across 3 centres over 3 years (<1/centre/month), assuming an estimated 10% dropout, and 50% proceeding to adrenalectomy, permits 90% power at alpha=0.01 of detecting superiority of metomidate vs AVS in predicting hierarchical primary outcomes. The 25 patient extension, on the same assumptions regarding dropouts and proportion proceeding to surgery, will also provide 90% power to show non inferiority of 11C-metomidate PET CT in relation to AVS, within a margin of 18%. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT02945904
Study type Observational
Source Queen Mary University of London
Contact Morris Brown, Prof
Phone 2078823901
Email morris.brown@qmul.ac.uk
Status Recruiting
Phase
Start date October 2016
Completion date November 30, 2021

See also
  Status Clinical Trial Phase
Completed NCT02885662 - Study of CS-3150 in Patients With Primary Aldosteronism N/A
Withdrawn NCT02096939 - Microvascular Function in Primary Aldosteronism N/A
Completed NCT01728493 - Primary Aldosteronism in General Practice: Organ Damage, Epidemiology and Treatment N/A
Recruiting NCT06228677 - Comparison of Catecholamine Concentrations in Venous Blood During Selective Adrenal Artery Embolization
Recruiting NCT06047912 - Screening for Primary Aldosteronism in Hypertension With 24-hour URinary aLdosterone
Recruiting NCT04991961 - Effect of Anti-hypertensive Medications on the Diagnostic Accuracy in Screening for Primary Aldosteronism
Recruiting NCT05405101 - Randomised Trial Comparing Thermal Ablation With Adrenalectomy in the Treatment of Unilateral Asymmetric PA N/A
Recruiting NCT05501080 - The Effect of SAAE on Ventricular Remodeling in PA Patients N/A
Recruiting NCT05826080 - Effect of Adrenocorticotropic Hormone Stimulation During Adrenal Vein Sampling in Primary Aldosteronism
Recruiting NCT05973604 - Prevalence of Primary Aldosteronism in Atrial Fibrillation
Completed NCT04179019 - Calcium Channel Blockade in Primary Aldosteronism Phase 2
Completed NCT03500120 - Diagnostic Accuracy of Seated Saline Suppression Test for Primary Aldosteronism
Recruiting NCT04213963 - Prospective Study on Primary Aldosteronism in Resistant Hypertension
Completed NCT05435703 - Renal Cysts and Primary Aldosteronism
Enrolling by invitation NCT02257450 - Primary Aldosteronism in Malaysia: A Nationwide Multicentre Study N/A
Recruiting NCT05561361 - The Effect of SAAE on Vascular Endothelial Function in PA Patients
Completed NCT03398785 - Adrenal Artery Ablation Treats Primary Aldosteronism Phase 3
Recruiting NCT04428827 - Outcome of Patients With Primary Aldosteronism
Recruiting NCT03224312 - Chongqing Primary Aldosteronism Study
Completed NCT02756754 - Radiofrequency Ablation for Aldosterone-producting Adenoma in Patients With Primary Aldosteronism N/A