Clinical trial NCT01188369: Effects of Levosimendan in Patients Eligible for Aortic Valve Replacement With Left Ventricular Hypertrophy
Official title: Effects of Levosimendan on Systolic Deformation and Diastolic Function in Patients Eligible for Aortic Valve Replacement With Left Ventricular Hypertrophy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Diastolic Dysfunction
Left Ventricular Hypertrophy
Keywords: levosimendan
heart failure
inotropics
diastolic dysfunction
left ventricular hypertrophy
aortic valve stenosis
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2010-08-25
Enrollment: 20
Sex: ALL
Minimum age (years): 30
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a clinical, randomised, double-blinded study in which patients eligible for aortic valve replacement are enrolled. Patients receive infusion of either levosimendan or placebo 4 hours prior to surgery and until the end of surgery.

Detailed description: Levosimendan or placebo will be infusion for approximately 4 hours prior to aortic valve replacement in patients with severe hypertrophy of the left ventricle and echocardiographic signs of diastolic dysfunction. Outcome measures will be obtained at some of the following:

* Approximately 4 hours prior to surgery. Baseline. Start of levosimendan/placebo infusion
* Immediately before surgery
* After induction of anaesthesia and before "knife time" = start of surgery.
* At the end of surgery: Levosimendan infusion will stop.
* Approximately 4 hours after surgery immediately before extubation.
* Approximately 21 hours after surgery
* Approximately 96 hours after surgery (day 4)
* 6 months after surgery

Outcome measures are comprised of invasive measurements, blood samples, transthoracic echocardiography and transoesophageal echocardiography focusing on measures of systolic and diastolic function of the heart.

Interim analysis will be conducted after 30 included patients.

Eligibility criteria: Inclusion Criteria:

* Eligible for aortic valve replacement
* EF \> 45%
* Left ventricular posterior wall \> 12mm
* Sinus rhythm

Exclusion Criteria:

* Concomitant bypass operation
* Severe mitral insufficiency
* Active endocarditis
* Insufficient ultrasound opportunity
* Systolic blood pressure \< 100 mmHg
* moderate-severe renal failure
* allergy to levosimendan
* lack of patient consent Pregnancy or status of lactating
* Fertile women who do not use relevant anticonception

Primary outcomes:
measure: E/E'(Unitless)
timeFrame: 4 hours before operation until 21 hour after operation
Secondary outcomes:
measure: Isovolumetric Relaxation Time (IVRT) (s)
timeFrame: 4 hours before surgery until 1 hour before operation
measure: Ejection Fraction (Per Cent)
timeFrame: At start of operation until end of operation, approximately 3 hours
measure: Cardiac Index (l/Min/m2)
timeFrame: 4 hours before operation until 1 hour before operation
measure: Central Venous Pressure (mmHg)
timeFrame: 4 hours before operation until 1 hours before operation
measure: Pulmonary Artery Pressures (mmHg)
timeFrame: 4 hours before operation until 1 hour before operation
measure: Systemic Arterial Pressure (mmHg)
timeFrame: 4 hours before operation until 1 hour before operation
measure: N-terminal Pro Brain Natriuretic Peptide (NT proBNP)(pg/ml)
timeFrame: 4 hours before operation until 4 hours after operation
measure: Troponin T (ug/l)
timeFrame: 4 hours before operation until 4 hours after operation
measure: Lactate (mmol/l)
timeFrame: 4 hours before operation until 4 hour after operation
measure: Mixed Venous Oxygenation (Per Cent)
timeFrame: 4 hours before operation until 4 hour after operation
measure: E/A Ratio (Unitless)
timeFrame: At the start of operation until the end of operationon, approximately 3 hours
measure: Regional Longitudinal Strain (Unitless)
timeFrame: At the start of operation until the end of operation, approximately 3 hours
measure: Need for Conventional Inotropical Agents
timeFrame: From start of operation until 5 days after operation
measure: Intravenous Fluid Requirement (l)
timeFrame: Within 24 hours from start of operation
measure: Operation Time (Minutes)
timeFrame: From "knife start" until "knife end", approximately 3 hours
measure: Time on Heart-lung Machine (Minutes)
timeFrame: From time of cardioplegia until selfsufficient cardiac action, approximately 1 hour
measure: Intubation Time (Minutes)
timeFrame: From intubation until extubation, approximately 6 hours
measure: Postoperative Admission Time at Intensive Care Unit (Hours)
timeFrame: From admission to the intensive care unit until discharge from intensive care unit, approximately 24 hours
measure: No. of Patients With Adverse Events
timeFrame: -4 hours until + 96 hours with respect to start of operation
measure: No. of Patients With Adverse Event
timeFrame: -4 hours until + 96 hours with respect to start of operation
measure: No. of Patients With Adverse Event
timeFrame: 4 hours before operaton until 1 hour before operaton
measure: No. of Patients With Adverse Event.
timeFrame: 4 hours before operation until 1 hour before operation
measure: No. of Patients With Adverse Event
timeFrame: 4 hours before operation until approximately 1 hour before operation
measure: Regional Longitudinal Strain (Unitless)
timeFrame: 4 hours before until 1 hour before start of operation
measure: Ejection Fraction (Per Cent)
timeFrame: 1 hour before until 21 hour after start of operation
measure: Ejection Fraction (Per Cent)
timeFrame: 21 hours after operation until 96 hours after start of operation
measure: Ejection Fraction (Per Cent)
timeFrame: 96 hours after operation until 6 months after operation
measure: Regional Longitudinal Strain (Unitless)
timeFrame: Froml the end of operation until approx 4 hours after operation
measure: E/A Ratio (Unitless)
timeFrame: At the end of operationon until approx 4 hours after operation
measure: Left Ventricular Rotation (Degrees)
timeFrame: 96 hour after operation until 6 months after operation
measure: Mixed Venous Oxygenation (Per Cent)
timeFrame: 4 hours after operation until 21 hours after operation
measure: Lactate (mmol/l)
timeFrame: 4 hours after operation until 21 hours after operation
measure: Troponin T (ug/l)
timeFrame: 4 hours after operation until 21 hours after operation
measure: Troponin T (ug/l)
timeFrame: 21 hours after operation until 96 hours after operation
measure: N-terminal Pro Brain Natriuretic Peptide (NT proBNP)(pg/ml)
timeFrame: 4 hours after operation until 21 hours after operation
measure: N-terminal Pro Brain Natriuretic Peptide (NT proBNP)(pg/ml)
timeFrame: 21 hours after operation until 96 hours after operation
measure: Systemic Arterial Pressure (mmHg)
timeFrame: 1 hour before operation until start of operation
measure: Systemic Arterial Pressure (mmHg)
timeFrame: Start of operation until the end of operation, approximately 3 hours
measure: Systemic Arterial Pressure (mmHg)
timeFrame: End of operation until approx 4 hours after operation
measure: Systemic Arterial Pressure (mmHg)
timeFrame: 4 hours after operation until 21 hours after operation
measure: Pulmonary Artery Pressures (mmHg)
timeFrame: 1 hour before operation until start of operation
measure: Pulmonary Artery Pressures (mmHg)
timeFrame: Start of operation until end of operation, approximately 3 hours
measure: Pulmonary Artery Pressures (mmHg)
timeFrame: End of operation until approx 4 hours after operation
measure: Pulmonary Artery Pressures (mmHg)
timeFrame: 4 hours after operation until 21 hours after operation
measure: Regional Longitudinal Strain (Unitless)
timeFrame: 1 hour before start of operation until 21 hours after operation
measure: Regional Longitudinal Strain (Unitless)
timeFrame: 21 hours after operation until 96 hours after operation
measure: Regional Longitudinal Strain (Unitless)
timeFrame: 96 hours after operation until 6 months after operation
measure: Central Venous Pressure (mmHg)
timeFrame: 1 hour before operation until start of operation
measure: Central Venous Pressure (mmHg)
timeFrame: Start of operation until end of operation, approximately 3 hours
measure: Central Venous Pressure (mmHg)
timeFrame: End of operation until approx 4 hours after operation
measure: Central Venous Pressure (mmHg)
timeFrame: 4 hours after operation until 21 hours after operation
measure: Peak Systolic Velocity (m/s)
timeFrame: 1 hour before operation until 21 hours after operation
measure: Peak Systolic Velocity (m/s)
timeFrame: 21 hours after operation until 96 hours after operation
measure: Peak Systolic Velocity (m/s)
timeFrame: 96 hours after operation until 6 months after operation
measure: Tricuspid Annular Plane Systolic Excursion (TAPSE) (mm)
timeFrame: 1 hour before operation until 21 hours after operation
measure: Tricuspid Annular Plane Systolic Excursion (TAPSE) (mm)
timeFrame: 21 hours after operation until 96 hours after operation
measure: Tricuspid Annular Plane Systolic Excursion (TAPSE) (mm)
timeFrame: 96 hours after operation until 6 months after operation
measure: E/A-ratio (Unitless)
timeFrame: 1 hour before operation until 21 hours after operation
measure: E/A-ratio (Unitless)
timeFrame: 21 hours after operation until 96 hours after operation
measure: E/A-ratio (Unitless)
timeFrame: 96 hours after operation until 6 months after operation
measure: E'/A'-Ratio (Unitless)
timeFrame: 1 hour before operation until 21 hours after roperation
measure: E'/A'-Ratio (Unitless)
timeFrame: 21 hours after operation until 96 hours after operation
measure: E'/A'-Ratio (Unitless)
timeFrame: 96 hours after operation until 6 months after operation
measure: Isovolumetric Relaxation Time (IVRT) (s)
timeFrame: 1 hour before operation until 21 hours after operation
measure: Isovolumetric Relaxation Time (IVRT) (s)
timeFrame: 21 hours after operation until 96 hours after operation
measure: Isovolumetric Relaxation Time (IVRT) (s)
timeFrame: 96 hours after operation until 6 months after operation
measure: Ejection Fraction (Per Cent)
timeFrame: End of operation until approx. 4 hours after operation
measure: Isovolumetric Relaxation Time (IVRT) (s)
timeFrame: End of operation until approx. 4 hours after operation
measure: Cardiac Index (l/Min/m2)
timeFrame: 1 hour before operation until start of operation
measure: Cardiac Index (l/Min/m2)
timeFrame: Start of operation until end of operation, approximately 3 hours
measure: Cardiac Index (l/Min/m2)
timeFrame: End of operation operation until approx. 4 hours after operation
measure: Cardiac Index (l/Min/m2)
timeFrame: 4 hours after operation until 21 hours after operation
measure: Inflammatory Parameters
timeFrame: 4 hours before operation until 21 hours after operation
measure: Inflammatory Parameters
timeFrame: 21 hours after operation until 96 hours after operation
measure: E/A-ratio (Transoesophageal)
timeFrame: from start of operation until end of operation, approximately 3 hours
measure: E/A-ratio (Transoesophageal)
timeFrame: from end of operation until approximately 4 hours after operation
measure: Urine Clearance
timeFrame: from start of operation until 24 hours after operation
Other outcomes:
Locations:
city: Århus N
country: Denmark
facility: Department of Anaesthesiology
state: Region Midtjylland
Study officials:
affiliation: Department of Anaesthesiology
name: Peter Juhl-Olsen, M.D.
role: PRINCIPAL_INVESTIGATOR
References: