Plain English Summary
Background and study aims
Primary hyperparathyroidism (PHPT) occurs when too much of an hormone called parathyroid hormone (PHT) is produced, leading to high levels of calcium in the blood. This may be associated with cardiovascular (heart) problems such as myocardial ischemia (decreased blood flow to the heart), arrhythmia (heart rhythm problems), arterial hypertension (high blood pressure), endothelial dysfunction (problems with the inner lining of blood vessels) and metabolic abnormalities. Increasing evidence suggests a link between PHT and another hormone called aldosterone. Primary aldosteronism occurs when too much aldosterone is produced. It is suggested that the treatment of either disease (primary aldosteronism or PHPT) has a positive effect on the other.
The aim of the study is to find out whether aldosterone inhibition by the drug eplerenone has beneficial effects on the cardiovascular system, bone metabolism and kidney function. The expected outcome is that in PHPT patients treatment with eplerenone decreases PTH levels, improves bone metabolism and decreases blood pressure and cardiovascular pathology.
Who can participate?
Male and female patients aged 18 and over, who have asymptomatic PHPT (i.e., without symptoms) and do not meet the guidelines for surgical treatment, or patients with symptomatic PHPT (i.e., with symptoms) in whom surgery is recommended but not performed because of patient and/or physician preference or medical reasons.
What does the study involve?
Participants will be randomly allocated to be treated for 8 weeks with either eplerenone or a dummy drug called a placebo.
What are the possible benefits and risks of participating?
Eplerenone may have additional positive health effects (e.g. muscular) which may be of additional benefit for the study participants. Previous studies documented no significant differences in the incidence of severe adverse events in participants receiving eplerenone compared to those on placebo. To minimize potential harm to the patients, there will be several visits taking place more frequently in the early phase of the study, to guarantee timely detection of potential adverse effects.
Where is the study run from?
Medical University of Graz, Department of Internal Medicine, Division of Cardiology and Division of Endocrinology and Metabolism (Austria).
When is the study starting and how long is it expected to run for?
The study started in July 2012 and will run for three years until June 2015.
Who is funding the study?
Austrian National Bank (Austria).
Who is the main contact?
Dr Andreas Tomaschitz
andreas.tomaschitz@gmx.at
Trial website
Contact information
Type
Scientific
Primary contact
Dr Andreas Tomaschitz
ORCID ID
Contact details
Medical University of Graz
Department of Internal Medicine
Divison of Cardiology
Auenbruggerplatz 15
Graz
8036
Austria
+43 316 385 12544
andreas.tomaschitz@gmx.at
Additional identifiers
EudraCT number
2011-005683-21
ClinicalTrials.gov number
Protocol/serial number
4.0: 30.01.2012
Study information
Scientific title
Effects of eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism: a randomized, double-blind, placebo-controlled trial
Acronym
EPATH
Study hypothesis
In patients with primary hyperparathyroidism (PHPT) Mineralocorticoid-receptor (MR) blockade with eplerenone improves cardiovascular and bone health.
We propose a randomized controlled trial to test this hypothesis in PHPT patients. The expected outcome is that in PHPT patients inhibition of aldosterone mediated effects by MR-blockade with eplerenone results in:
1. A decrease of PTH levels
2. Positive effects on bone metabolism reflected by markers of bone metabolism
3. Decreased blood pressure and cardiovascular pathology
The majority of studies noted that even mild forms of primary hyperparathyroidism (PHPT) are associated with higher risk of cardiovascular morbidity and mortality. The precise mechanisms underlying these associations in patients with PHPT their potential role as therapeutic targets are currently not fully elucidated.
Increasing evidence suggests a clinically relevant interplay between aldosterone and PTH. Most studies in humans identified a positive correlation between aldosterone and PTH levels particularly in patients with PHPT. Some studies advocated that PTH is a direct or indirect stimulus for of aldosterone synthesis and secretion in the adrenal, This is of utmost clinical importance, as several studies documented that aldosterone is a major cardiovascular risk factor. Given the linkage between aldosterone and PTH it is suggested that treatment of either disease (primary aldosteronism and PHPT) results in positive effects in the other hormone system.
Ethics approval
Ethics Committee of Medical University of Graz, Austria, 12 December 2011, ref: 24-032 ex 11/12
Study design
Single-center randomized double-blind placebo-controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Primary hyperparathyroidism (PHPT)
Intervention
Overall, 110 participants will be randomized to 8 weeks of double-blind treatment with eplerenone 25mg and 50 mg once daily, respectively.
Eplerenone will be initiated at 25 mg once daily and titrated to 50 mg once daily after 4 weeks as tolerated by the patient. The study consists of a 8-weeks, double-blind, randomized (active) treatment period: after 8 weeks of randomized treatment the primary outcome [mean change of iPTH(1-84) levels] will be evaluated.
Intervention type
Drug
Phase
Phase III
Drug names
Eplerenone
Primary outcome measures
Mean change of iPTH(1-84) levels from baseline after 8 weeks
Secondary outcome measures
1. Mean change of 24-hour systolic and diastolic ambulatory BP levels from baseline after 8 weeks
2. Mean change of NT-pro-BNP and osteoprotegerin from baseline after 8 weeks
3. Mean change of biomarkers of bone metabolism: osteocalcin, β-CrossLaps, bone alkaline phosphatase
Overall trial start date
01/07/2012
Overall trial end date
30/06/2015
Reason abandoned
Eligibility
Participant inclusion criteria
1. Written informed consent
2. Patients with PHPT:
2.1. Asymptomatic PHPT who do not meet guidelines for surgical treatment
2.2. Symptomatic PHPT in whom surgery is recommended, but not performed because of patient and/or physician preference or perceived medical contraindications
3. Age ≥ 18 years
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 110 adult men and women
Participant exclusion criteria
1. 25 - hydroxy vitamin D [25(OH)D] levels < 20 ng/dl (50 nmol/liter)
2. Estimated glomerular filtration rate (eGFR; according to the MDRD formula) ≤ 50 ml/min
3. Serum potassium > 5.0 mEq/L (mmol/L) at baseline or > 5.5 mEq/L (mmol/L) during active study period
4. Pregnancy or lactating women
5. Drug intake as part of another clinical study 4 weeks before enrolment into the EPATH study and/or during the active study period
6. Any disease with an estimated life expectancy below 1 year
7. Chemotherapy or radiation therapy during the study
8. Intolerance to eplerenone or any ingredient occurring in eplerenone
9. Severe acute or chronic liver diseases (Child-Pugh Class C)
10. Concurrent intake of potassium sparing drugs, e.g. diuretics (amiloride and triamterene) or CPY3A4-inhibitors and ongoing potassium supplementation
Recruitment start date
01/07/2012
Recruitment end date
30/06/2015
Locations
Countries of recruitment
Austria
Trial participating centre
Medical University of Graz
Graz
8036
Austria
Sponsor information
Organisation
Medical University of Graz (Austria)
Sponsor details
c/o Dr Andreas Tomaschitz
MD
Medical University of Graz
Department of Internal Medicine
Division of Cardiology
Auenbruggerplatz 15
Graz
8036
Austria
+43 316 385 12544
andreas.tomaschitz@gmx.at
Sponsor type
University/education
Website
Funders
Funder type
Government
Funder name
Austrian National Bank (Austria) (Jubiläumsfond ref: 14621)
Alternative name(s)
Austrian National Bank, OeNB
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
Austria
Funder name
Medical University of Graz (Austria)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary