Is metomidate PET-CT superior to adrenal venous sampling in predicting outcome from adrenalectomy in patients with primary hyperaldosteronism?
| ISRCTN | ISRCTN91387205 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN91387205 |
| ClinicalTrials.gov number | NCT02945904 |
| Secondary identifying numbers | 011149; EME 14/145/09 |
- Submission date
- 13/12/2016
- Registration date
- 12/01/2017
- Last edited
- 13/02/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English summary of protocol
Background and study aims
Hypertension (high blood pressure) is a major risk factor for stroke, heart attack, and kidney disease.
Approximately 16 million people in the UK have hypertension and over 60,000 preventable deaths per
year from stroke and heart attack are down to inadequate blood pressure control. Most cases of hypertension have no identifiable cause, but in some patients an underlying condition can be found. One possible cause of hypertension is Conn’s syndrome in which the adrenal glands (glands located on top of the kidneys) produce too much of a hormone called aldosterone. This hormone causes the body to retain salt, leading to the development of hypertension. Conn’s syndrome carries an even higher risk of stroke or heart attack than other forms of hypertension. It is usually diagnosed by measuring aldosterone levels in a blood sample. In at least half of patients with Conn’s syndrome, the condition is due to a benign (non-cancerous) nodule (lump) in one of the adrenal glands. The discovery and removal of these nodules often allows the hypertension to be cured, avoiding the life-long need to take drugs. The current diagnostic test these nodules involves taking blood from both adrenal glands, which can be a difficult and demanding procedure. This study is looking at a newly developed, special type of CT scan, which makes nodules light up on the scan if visible. The aim of this study is to find out whether this new adrenal scan (which is quick and painless) is more accurate than the existing test for diagnosing adrenal nodules.
Who can participate?
Adult patients with high aldosterone levels
What does the study involve?
All participants have the two investigations performed in a random order. The first investigation involves having a small tube (cannula) inserted into the veins supplying the adrenal glands to take samples of blood. These samples are then tested in the laboratory. The second investigation involves having a body scan to look for nodules. The scan lasts for approximately an hour and for the three days before having the scan patients take a type of steroid medication called dexamethasone.
What are the possible benefits and risks of participating?
Participants benefit from undergoing extensive examinations as well as having follow- up care with a specialised research team. If the investigations locate the aldosterone producing adenoma, once removed it is anticipated that high blood pressure will either be cured or require less medication. The main disadvantage is that patients will be asked to attend on two days (once for PET CT scan and again for adrenal vein sampling) rather than just for AVS which is the usual diagnostic test offered. The radiation exposure from the 11C metomidate PET CT scan is 8 millisieverts (mSv) and is similar to the dose from a whole-body computed tomography (CT) scan, or to about 3 years’ exposure to background radiation in the UK. This is equal to approximately a 1 in 3000 risk of developing cancer and to put this into context, the natural life time incidence of developing cancer is estimated to be about 1 in 3.
Where is the study run from?
Queen Mary University of London (UK)
When is the study starting and how long is it expected to run for?
September 2015 to November 2022
Who is funding the study?
National Institute for Health Research (UK)
Who is the main contact?
Mrs Jackie Salsbury
jackie.salsbury@qmul.ac.uk
Contact information
Scientific
The Barts Heart Centre
William Harvey Research Institute
Queen Mary University of London
Charterhouse Square
London
EC1M 6B
United Kingdom
Study information
| Study design | Observational multi-centre cohort study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cohort study |
| Study setting(s) | Hospital |
| Study type | Diagnostic |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | Is metomidate PET-CT superior to adrenal venous sampling in predicting outcome from adrenalectomy in patients with primary hyperaldosteronism? (MATCH): a multi-centre, randomised, within-patient comparison of diagnostic techniques |
| Study acronym | MATCH |
| Study objectives | The purpose of this clinical trial is to improve prediction of outcomes from surgical intervention in patients with primary aldosteronism, and evaluate the merits of noninvasive metomidate PET CT versus adrenal vein sampling in the diagnosis of surgically correctable aldosteronism. More details can be found at: https://www.journalslibrary.nihr.ac.uk/programmes/eme/1414509/#/ |
| Ethics approval(s) | London – Dulwich Research Ethics Committee, 05/08/2016, ref: 16/LO/1242 |
| Health condition(s) or problem(s) studied | Primary aldosteronism |
| Intervention | This is an observational cohort study which takes place within existing secondary and tertiary care practice of the NHS. It is a multi-centre study in which all participants to 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. 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 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) |
| Intervention type | Other |
| Primary outcome measure | 1. Aldosterone renin ratio in patients with primary aldosteronism (Conn's adenoma) is measured using serum aldosterone and renin ratio at baseline and 6 months after treatment 2. Home systolic blood pressure is measured using an automatic brachial blood pressure monitor at baseline and 6 months after treatment |
| Secondary outcome measures | 1. Number of patients achieving home systolic blood pressure <140mmHg on no treatment is measured by an automatic brachial blood pressure monitor at baseline and 6 months after treatment 2. Number of participants requiring less antihypertensive medication following treatment is measured using class and dosage of antihypertensive medications at baseline and 6 months after treatment 3. SUV max ratios between adenoma and normal adrenal are measured using 11-C Metomidate PET CT scan at baseline and 6 months after treatment 4. Reduction in home systolic blood pressure mmHg on 4-week spironolactone therapy is measured using an automatic brachial blood pressure monitor at baseline and 4 weeks 5. High sensitivity troponin serum level is measured using serum troponin levels at baseline and 6 months after treatment 6. Serum brain natriuretic peptide level is measured using serum brain natriuretic levels at baseline and 6 months after treatment |
| Overall study start date | 10/09/2015 |
| Completion date | 30/11/2022 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 140 |
| Total final enrolment | 143 |
| Key inclusion criteria | 1. Male or female age >18 years 2. Diagnosis of PHA based on published Endocrine Society consensus guidelines 3. Patients will be enrolled/consented when they have had each of the following: 3.1. At least one paired measurement of plasma renin and aldosterone, measured off spironolactone, showing an elevated ARR 3.2. Either a plasma aldosterone >190 pmol/L after saline infusion or ‘spontaneous hypokalemia + plasma renin below detection levels + plasma aldosterone > 550 pmol/L)’ (as per Endocrine Society guidance) 3.3. A CT or MRI scan of the adrenals with probable or definite adenoma(s) 4. Patients with elevated ARR can be put forward for consideration by the MDT as exceptional cases in whom spironolactone is not (fully) withdrawn, and/or saline suppression is not performed, IF: 4.1. Plasma Aldosterone > 450 pmol/L AND plasma renin <0.5 pmol/ml/hr (<9 mU/L) if measured on treatment with ACEI (Lisinopril >=20 mg or equivalent) or ARB (Losartan 100 mg or equivalent); OR 4.2. Age <40 AND definite adrenal adenoma on CT or MRI Patients whose CT/MRI does not show probable or definite adenoma must also be reviewed by MDT before enrolment/consent 5. All patients will have a positive Aldosterone renin ratio (ARR) serum measurement with another local diagnostic confirmatory test as specified from local specialised APA Guidelines. This is often standard cross-sectional imaging by CT or MR scanning. Any exception to recommended diagnostic criteria will be subject to approval by monthly MDT |
| Key exclusion criteria | 1. Those patients who indicate that they are unlikely to proceed with surgery will not be recruited, because there will be no outcome change in blood pressure, restoration of normal renin/angiotensin physiology) against which to compare the accuracy of the two Investigations 2. Patients contraindicated for spironolactone therapy 3. Any patients continuing on beta-blockers or direct renin blockers 4. Pregnant/breastfeeding females or women unable/unwilling to take secure contraceptive precautions whilst undergoing investigations 5. Patients unwilling/unable to take the dexamethasone required to prepare for a metomidate PET-CT scan 6. Any illness, condition or drug regimen that is considered a contraindication by the PI |
| Date of first enrolment | 01/12/2016 |
| Date of final enrolment | 01/10/2019 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
William Harvey Research Institute
Charterhouse Square
London
EC1M 6BQ
United Kingdom
Sponsor information
University/education
Joint Research Management Office
Queen Mary Innovation Centre
5 Walden Street
London
E1 2EF
England
United Kingdom
"ROR" |
https://ror.org/026zzn846 |
|---|
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/12/2021 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan | The current data sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No | ||
| Protocol (other) | 16/01/2023 | 13/02/2024 | No | No | |
| Results article | 16/01/2023 | 13/02/2024 | Yes | No | |
| Statistical Analysis Plan | 16/01/2023 | 13/02/2024 | No | No |
Editorial Notes
13/02/2024: Publication reference, total final enrolment, protocol and statistical analysis plan added.
23/06/2022: The overall trial end date has been changed from 01/12/2020 to 30/11/2022 and the plain English summary has been updated accordingly.
18/07/2017: Internal edit.
