Condition category
Nutritional, Metabolic, Endocrine
Date applied
22/09/2011
Date assigned
20/02/2012
Last edited
23/01/2014
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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

http://www.meduni-graz.at/

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

Publication citations

Additional files

Editorial Notes