EFFECTS OF ORAL LEVOSIMENDAN ON AMBULATORY ELECTROCARDIOGRAPHIC VARIABLES AND CEREBROVASCULAR REACTIVITY IN PATIENTS WITH RECENT STROKE OR TIA. A RANDOMISED, DOUBLE BLIND, PLACEBO-CONTROLLED, DOSE FINDING, MULTICENTRE STUDY WITH PARALLEL GROUP DESIGN - ELECTRO

• Register: EUCTR
• Last refreshed on: 14 August 2012
• Main ID: EUCTR2007-007197-31-HU
• Date of registration: 26/05/2008
• Prospective Registration: Yes
• Primary sponsor: Orion Corporation Orion Pharma
• Public title: EFFECTS OF ORAL LEVOSIMENDAN ON AMBULATORY ELECTROCARDIOGRAPHIC VARIABLES AND CEREBROVASCULAR REACTIVITY IN PATIENTS WITH RECENT STROKE OR TIA. A RANDOMISED, DOUBLE BLIND, PLACEBO-CONTROLLED, DOSE FINDING, MULTICENTRE STUDY WITH PARALLEL GROUP DESIGN - ELECTRO
• Scientific title: EFFECTS OF ORAL LEVOSIMENDAN ON AMBULATORY ELECTROCARDIOGRAPHIC VARIABLES AND CEREBROVASCULAR REACTIVITY IN PATIENTS WITH RECENT STROKE OR TIA. A RANDOMISED, DOUBLE BLIND, PLACEBO-CONTROLLED, DOSE FINDING, MULTICENTRE STUDY WITH PARALLEL GROUP DESIGN - ELECTRO
• Date of first enrolment: 10/07/2008
• Target sample size: 45
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-007197-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Finland, Germany, Hungary, Sweden

Key inclusion & exclusion criteria

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. Other inclusion criteria are:
• Maintenance treatment with an angiotensin II receptor blocker or angiotensin converting enzyme inhibitor, cholesterol lowering agent (preferably 3-hydroxy-3-methyl-glutaryl-Coenzyme A [HMG-CoA] reductase inhibitor) and antiaggregatory agent started at least 1 month before the screening visit

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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Stroke or TIA due to cardiac embolism, vasculitis or arterial dissection
• Severe hemiparesis or dysphasia inhibiting the ability to fully comply with the study protocol requirements
• Haemodynamically significant uncorrected valve disease or hypertrophic cardiomyopathy or restrictive cardiomyopathy
• Acute myocardial infarction or any other acute coronary event within 1 month before the screening visit
• Cardiovascular surgery (e.g. carotid endarterectomy, coronary by-pass) or angioplasty or any other major surgery within 1 month before the screening visit
• Patients who are scheduled for coronary by-pass or angioplasty, or carotid endarterectomy or any major surgery during the planned study period
• History of life-threatening ventricular arrhythmia within 3 months before randomization defined as an episode of resuscitated sudden death, ventricular fibrillation (VF) or sustained or haemodynamically destabilising ventricular tachycardia (VT)
• History of Torsades de Pointes (TdP) or family history of long QT-syndrome
• Anticipated technical problems in transcranial Doppler (TCD) assessments (e.g. poor insonation of the temporal bone window, patient’s inability to hold breath for at least 30 seconds)
• Heart rate (HR) < 50 or > 100 bpm in the 12-lead ECG or as an average in the 24-hour ambulatory Holter recording at screening
• Systolic blood pressure (SBP) < 100 mmHg or > 180 mmHg, or diastolic blood pressure (DBP) > 100 mmHg at screening
• Ventricular tachycardia (wide complex tachycardia > 100/min, = 3 consecutive beats) in the 24-hour ambulatory Holter recording at screening
• Episode of atrial fibrillation or atrial flutter lasting > 60 seconds in 24-h ambulatory Holter recording at screening
• Second or third degree atrioventricular (AV) block in the 12-lead ECG or in the 24-h ambulatory Holter recording at screening
• Potassium (K) < 3.7 mmol/l or > 5.5 mmol/l at screening
• Creatinine > 170 µmol/l at screening or on dialysis
• Blood haemoglobin <10 g/dl at screening
• Clinically significant hepatic impairment at the discretion of the investigator.
• Women of reproductive age without a negative pregnancy test and without a commitment to using an acceptable method of barrier or hormonal contraception (e.g. condoms, diaphragms, oral contraceptives and long acting progestin agents) if sexually active during the study and for 1 month after the last dose of the study treatment. Women who are postmenopausal (1 year since last menstrual cycle), surgically sterilised or who have undergone a hysterectomy are considered not to be reproductive and can be included.
• Other serious diseases limiting the life expectancy considerably (e.g. end-stage cancer).
• Participation in a clinical trial with any experimental treatment within 30 days prior to the screening visit or previous participation in the present study.
• Hypersensitivity to levosimendan.
• Administration of levosimendan within 30 days prior to screening visit.
• Any other condition that in the opinion of the investigator could create a hazard to the subject safety, or interfere with study procedures or with the interpretation of study results.
• A predictable poor compliance or inability to communicate well with the study personnel.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Stroke or TIA
MedDRA version: 9.1 Level: LLT Classification code 10042244 Term: Stroke

Intervention(s)

Product Name: Levosimendan Capsules 0.5 mg
Pharmaceutical Form: Capsule*
INN or Proposed INN: Levosimendan
CAS Number: 141505-33-1
Current Sponsor code: (-)-OR-1259
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Product Name: Levosimendan Capsules 0.125 mg
Pharmaceutical Form: Capsule*
INN or Proposed INN: Levosimendan
CAS Number: 141505-33-1
Current Sponsor code: (-)-OR-1259
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.125-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Product Name: Levosimendan Capsules 0.25 mg
Pharmaceutical Form: Capsule*
INN or Proposed INN: Levosimendan
CAS Number: 141505-33-1
Current Sponsor code: (-)-OR-1259
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.25-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Product Name: Levosimendan Capsules 1.0 mg
Pharmaceutical Form: Capsule*
INN or Proposed INN: Levosimendan
CAS Number: 141505-33-1
Current Sponsor code: (-)-OR-1259
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1.0-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: The secondary objectives are
• to evaluate the effect of oral levosimendan on cerebrovascular reactivity
• to evaluate the effect of oral levosimendan on biomarkers
• to evaluate the effect of oral levosimendan on thrombocyte aggregation
• to study the pharmacokinetics of different doses of levosimendan

Main Objective: 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.

Primary end point(s): Ventricular extrasystoles per hour (VES/h) in 24-h ambulatory ECG (Holter)

Secondary ID(s)

2007-007197-31-FI

3001088