Effects of eplerenone in patients with primary hyperparathyroidism
| ISRCTN | ISRCTN33941607 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN33941607 |
| EudraCT/CTIS number | 2011-005683-21 |
| Secondary identifying numbers | 4.0: 30.01.2012 |
- Submission date
- 22/09/2011
- Registration date
- 20/02/2012
- Last edited
- 18/09/2017
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English summary of protocol
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 this 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 are 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?
July 2012 to June 2015
Who is funding the study?
Austrian National Bank (Austria)
Who is the main contact?
Dr Andreas Tomaschitz
andreas.tomaschitz@gmx.at
Contact information
Scientific
Medical University of Graz
Department of Internal Medicine
Divison of Cardiology
Auenbruggerplatz 15
Graz
8036
Austria
| Phone | +43 (0)316 385 12544 |
|---|---|
| andreas.tomaschitz@gmx.at |
Study information
| Study design | Single-center randomized double-blind placebo-controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Effects of eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism: a randomized, double-blind, placebo-controlled trial |
| Study acronym | EPATH |
| Study objectives | In patients with primary hyperparathyroidism (PHPT) Mineralocorticoid-receptor (MR) blockade with eplerenone improves cardiovascular and bone health. The trialists 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(s) | Ethics Committee of Medical University of Graz, Austria, 12/12/2011, ref: 24-032 ex 11/12 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Eplerenone |
| Primary outcome measure | 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 study start date | 01/07/2012 |
| Completion date | 30/06/2015 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 110 adult men and women |
| Key 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 |
| Key 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 |
| Date of first enrolment | 01/07/2012 |
| Date of final enrolment | 30/06/2015 |
Locations
Countries of recruitment
- Austria
Study participating centre
8036
Austria
Sponsor information
University/education
c/o Dr Andreas Tomaschitz, MD
Medical University of Graz
Department of Internal Medicine
Division of Cardiology
Auenbruggerplatz 15
Graz
8036
Austria
| Phone | +43 (0)316 385 12544 |
|---|---|
| andreas.tomaschitz@gmx.at | |
| Website | http://www.meduni-graz.at/ |
"ROR" |
https://ror.org/02n0bts35 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Bank of Austria, Austrian National Bank, OeNB
- Location
- Austria
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/12/2017 | Yes | No |
Editorial Notes
18/09/2017: Publication reference added.
