Evaluation of the effect of a medicine called eplerenone in people with type II diabetes who have evidence of stiffening of the heart muscle

• Conditions: Asymptomatic left ventricular diastolic dysfunction in diabetes; MedDRA version: 17.0Level: PTClassification code 10052337Term: Diastolic dysfunctionSystem Organ Class: 10007541 - Cardiac disorders; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2011-006123-37-IE
• Lead Sponsor: Solvotrin Innovations Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-03-08
• Last Update Posted: 7 December 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1.Over 18 years of age
2.Ability to give informed consent
3.Type II diabetes mellitus
4.Diastolic dysfunction on Doppler-echocardiogram as evidenced by either LAVI >32ml/m2 and/or e' <10cm/s

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion Criteria

1.Age < 18 years at the time of randomisation
2.Type I diabetes mellitus
3.Administration of eplerenone or spironolactone within 30 days of randomisation
4.Patients with serum potassium level <3.5 or >5.0 mmol/L before randomization
5.Recent admission for acute cardiovascular event (e.g. ischemia) < 3 months
6.Defined history of heart failure, MI, coronary artery bypass grafting, stroke, transient ischemic attack or percutaneous coronary intervention within previous three months or known presence of hemodynamically relevant stenosis of the arteries perfusing the brain
7.Significant mitral regurgitation (significant mitral regurgitation will be defined as moderate or severe defined by echo-doppler imaging including extent of doppler signal, extent of proximal isovelocity surface area and pulmonary vein retrograde flow e.g. moderate mitral regurgitation will be regurgitant fraction >30% and/or proximal isovelocity surface area >0.4cm2)
8.Documented evidence (ECG) of atrial fibrillation
9.Prior documented LVEF <45% or qualitative moderate or severe LV systolic dysfunction
10.Revascularisation being actively considered
11.Haemodynamically severe valvular heart disease
12.Renal dysfunction (GFR < 50 mL/min/1.73m2)
i.The estimated GFR (eGFR) will be calculated using the following MDRD equation: eGFR (ml/min/1.73m2) = 186 (serum creatinine mg/dL)1.154 X (age)0.203 X (0.742 if subject is female) X (1.210 if subject is African American).
13.Patients with ongoing systemic or hepatic illness
14.Patients with severe hepatic insufficiency (Child-Pugh Class C)
15.Pregnant women
16.HbA1c (IFCC) >69mmol/mol
17.Diastolic BP >110 mmHg and a systolic BP >180 mmHg
18.Orthostatic hypertension, secondary hypertension or a history of severe or malignant hypertension
19.Any clinically significant, abnormal laboratory values that could preclude the patient from safely participating in the study.
20.Evidence of significant inflammatory disease, connective tissue disease, hepatic disease, metabolic bone disease which may alter parameters of collagen metabolism
21.Hypertrophic, restrictive or constrictive cardiomyopathy
22.Severe anaemia (Haemoglobin <8.0 g/dL)
23.Subjects with severe hepatic dysfunction defined by AST/ALT/ALP >3 times upper limit of normal
24.Recent major surgery (<6 months) (omit trauma)
25.Subjects with contraindications to MRI (including but not limited to)
a.Hypersensitivity to gadolinium containing contrast agents
b.Brain aneurysm clip
c.Implanted neural stimulator
d.Implanted cardiac pacemaker or defibrillator
e.Cochlear implant
f.Ocular foreign body (e.g. metal shavings)
g.Other implanted medical devices: (e.g. Swan Ganz catheter)
h.Implanted insulin pump
i.Metal shrapnel or bullet.
26.Contraindications to eplerenone therapy:
a.Hypersensitivity to eplerenone or any of the excipients.
b.Medications interacting with eplerenone therapy taken within 30 days of randomisation:
i.Patients receiving potassium-sparing diuretics, potassium-supplements
ii.Patients taking strong inhibitors of CYP 3A4 (eg itraconazole, ketoconazole, ritonavir, nelfinavir, erythromycin, clarithromycin, telithromycin and nefazodone).
iii.Patients taking strong CYP3A4 inducers (rifampicin, carbamazepine, phenytoin, phenobarbital, St John's Wort) should also be excluded as should patients treated with lithium, ciclosporin and tacrolimus.
iv.Patients taking amiodarone, d

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare the change in Left Atrial Volume Index (LAVI), measured by magnetic resonance imaging (MRI) in the treated group vs. the untreated group;Secondary Objective: Change in the level of markers of collagen turnover<br><br>Change in left ventricular mass index<br><br>Change in Doppler-Echocardiogaphic<br>markers of diastolic function including LAVI, mitral valve inflow pattern, tissue Doppler signal<br><br>Change in the level of markers of inflammation <br>;Primary end point(s): The primary endpoint of this study is the difference in the change in Left Atrial Volume Index (LAVI), measured by MRI in diabetic patients with asymptomatic left ventricular diastolic dysfunction treated with eplerenone and those not treated with eplerenone;Timepoint(s) of evaluation of this end point: Baseline, 6 months and 12 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Change in the level of markers of collagen turnover<br><br>Change in left ventricular mass index<br><br>Change in Doppler-Echocardiogaphic markers of diastolic function including LAVI, mitral valve inflow pattern, tissue Doppler signal<br><br>Change in the level of markers of inflammation <br>;Timepoint(s) of evaluation of this end point: Baseline (time 0), 2, 4, 6, 8, 10, 12 months for markers of collagen turnover and inflammatory markers<br><br>Echo doppler at 0, 6 and 12 months only