Effects of Oral Levosimendan on Ambulatory Electrocardiographic Variables

This is a prospective, multicentre, phase II, randomized, double-blind, placebo-controlled 2-arm parallel group study with 5 escalating dose-levels of oral levosimendan, each given for 13-18 days. The study population will be randomly allocated either to the levosimendan group or to the placebo group. The double-blind phase with either placebo or levosimendan is preceded by a 13-day long single-blind treatment with placebo (placebo run-in). The study consists of 9 visits (screening visit, 7 visits during the treatment period and an end-of-study visit). Each subject will be on study treatment (including placebo run-in) for 78-108 days and the duration of the study for each subject, including the screening and the end of study visit, is approximately 17 weeks.

Inclusion criteria

• Male and female patients 50 to 80 years of age with ischaemic stroke or TIA within 1 to 9 months before the screening visit.

Exclusion criteria

• Stroke or TIA due to cardiac embolism, vasculitis or arterial dissection
• Severe hemiparesis or dysphasia, haemodynamically significant uncorrected valve disease or hypertrophic cardiomyopathy or restrictive cardiomyopathy, any acute coronary event or angioplasty or any other major surgery within 1 month, any major surgery during the planned study period
• History of life-threatening ventricular arrhythmia within 3 months.
• History of Torsades de Pointes (TdP) or family history of long QT-syndrome
• Heart rate (HR) < 50 or > 100 bpm.
• Systolic blood pressure (SBP) < 100 mmHg or > 180 mmHg, or diastolic blood pressure (DBP) > 100 mmHg.
• Ventricular tachycardia.
• Episode of atrial fibrillation or atrial flutter lasting > 60 seconds.
• Second or third degree atrioventricular (AV) block.
• Potassium (K) < 3.7 mmol/l or > 5.5 mmol/l.
• Creatinine > 170 µmol/l or on dialysis.
• Blood haemoglobin <10 g/dl; clinically significant hepatic impairment.