Effects of Oral Levosimendan on Ambulatory Electrocardiographic Variables

Study Overview
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Brief Summary
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The primary objective is to explore the safety of low doses of oral levosimendan in patients with recent history of an ischaemic cerebrovascular event (stroke or TIA). The main focus will be on the evaluation of proarrhythmic potential of the different dose regimens.

Detailed Description
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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.

Official Title
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Effects of Oral Levosimendan on Ambulatory Electrocardiographic Variables and Cerebrovascular Reactivity in Patients With Recent Stroke or TIA.

Conditions
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Transient Ischemic Attack, Stroke

Intervention / Treatment
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* Drug: Levosimendan
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Levosimendan | Drug: Levosimendan<br>* from 0.125 mg to 2 mg in escalating doses<br>|
| Placebo Comparator: B<br>Placebo | Drug: Placebo<br>* Placebo capsules are identical in appearance to active capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24-h Holter reporting |  | every 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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An ischaemic cerebrovascular event (stroke or TIA)