Effects of Levosimendan in Patients Eligible for Aortic Valve Replacement With Left Ventricular Hypertrophy

Diastolic Dysfunction Clinical Trial

Official title:

Effects of Levosimendan on Systolic Deformation and Diastolic Function in Patients Eligible for Aortic Valve Replacement With Left Ventricular Hypertrophy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01188369
• Other study ID #: 1616
• Status: Terminated
• Phase: Phase 4
• Start date: September 2010
• Est. completion date: March 2013

Study information

• Verified date: August 2012
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 20
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Diastolic Dysfunction
• Hypertrophy
• Hypertrophy, Left Ventricular
• Left Ventricular Hypertrophy

Intervention

Drug:
• levosimendan
Intravenous infusion, 0,1ug/kg/min, duration 4 hours prior to operation and until the end of operation.
• placebo drug
Intravenous infusion, colour identical to levosimendan

Locations

Country	Name	City	State
Denmark	Department of Anaesthesiology	Århus N	Region Midtjylland

Sponsors (1)

Lead Sponsor	Collaborator
University of Aarhus

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	E/E'(Unitless)	Ration between early transmitral flow (E) and mitral annular tissue velocity(E'). This ratio is an echocardiographic index of diastolic function	4 hours before operation until 21 hour after operation
Secondary	Isovolumetric Relaxation Time (IVRT) (s)	Transthoracic measure of the time from aortic valve closure until mitral valve opening. A measure of diastolic function	4 hours before surgery until 1 hour before operation
Secondary	Ejection Fraction (Per Cent)	Transeosophageal echocardiography: Measure of systolic function	At start of operation until end of operation, approximately 3 hours
Secondary	Cardiac Index (l/Min/m2)	Invasive measurement measuring the cardiac output divided by calculated body surface area (DuBois formula)	4 hours before operation until 1 hour before operation
Secondary	Central Venous Pressure (mmHg)	Invasive measurement of pressure in the vena cava	4 hours before operation until 1 hours before operation
Secondary	Pulmonary Artery Pressures (mmHg)	Invasive measurement of mean pressure in the pulmonary artery	4 hours before operation until 1 hour before operation
Secondary	Systemic Arterial Pressure (mmHg)	Invasive measurements of arterial mean pressure	4 hours before operation until 1 hour before operation
Secondary	N-terminal Pro Brain Natriuretic Peptide (NT proBNP)(pg/ml)	blood sample reflecting stretch of the atrium/ventricle	4 hours before operation until 4 hours after operation
Secondary	Troponin T (ug/l)	Blood sample expressing damage to the myocytes	4 hours before operation until 4 hours after operation
Secondary	Lactate (mmol/l)	Arterial sampling of blood lactate	4 hours before operation until 4 hour after operation
Secondary	Mixed Venous Oxygenation (Per Cent)	Oxygen content (per cent of hemoglobin saturated) of venous blood in pulmonary artery	4 hours before operation until 4 hour after operation
Secondary	E/A Ratio (Unitless)	TEE ratio between early (E) transmitral flow and late (A) transmitral flow. An index of diastolic function althought not validated properly yet when measured from the oesophagus	At the start of operation until the end of operationon, approximately 3 hours
Secondary	Regional Longitudinal Strain (Unitless)	Transoesophageal echocardiographic (TEE) measure of systolic function. At this time not validated properly against acknowledged indices of systolic function.	At the start of operation until the end of operation, approximately 3 hours
Secondary	Need for Conventional Inotropical Agents	Conventional inotropics are comprised of all inotropics acting primarily through alfa- or beta- stimulation.	From start of operation until 5 days after operation
Secondary	Intravenous Fluid Requirement (l)	Total volume of intravenous fluid required including blood products.	Within 24 hours from start of operation
Secondary	Operation Time (Minutes)		From "knife start" until "knife end", approximately 3 hours
Secondary	Time on Heart-lung Machine (Minutes)		From time of cardioplegia until selfsufficient cardiac action, approximately 1 hour
Secondary	Intubation Time (Minutes)	Total time intubated including time of operation and in the intensive care ward	From intubation until extubation, approximately 6 hours
Secondary	Postoperative Admission Time at Intensive Care Unit (Hours)	Total admission time in the intensive care after operation	From admission to the intensive care unit until discharge from intensive care unit, approximately 24 hours
Secondary	No. of Patients With Adverse Events	Development of Ventricular tachycardia	-4 hours until + 96 hours with respect to start of operation
Secondary	No. of Patients With Adverse Event	Development of atrial flutter/fibrillation	-4 hours until + 96 hours with respect to start of operation
Secondary	No. of Patients With Adverse Event	Need for norepinephrine as an antagonist to the vasodilatatory effect of levosimendan	4 hours before operaton until 1 hour before operaton
Secondary	No. of Patients With Adverse Event.	Occurence of nausea	4 hours before operation until 1 hour before operation
Secondary	No. of Patients With Adverse Event	Occurence of headache	4 hours before operation until approximately 1 hour before operation
Secondary	Regional Longitudinal Strain (Unitless)	Index of systolic function derived from single transthoracic echocardiographic (TTE) projection	4 hours before until 1 hour before start of operation
Secondary	Ejection Fraction (Per Cent)	TTE: Index of systolic function	1 hour before until 21 hour after start of operation
Secondary	Ejection Fraction (Per Cent)	TTE: Index of systolic function	21 hours after operation until 96 hours after start of operation
Secondary	Ejection Fraction (Per Cent)	TTE: Index of systolic function	96 hours after operation until 6 months after operation
Secondary	Regional Longitudinal Strain (Unitless)	Transoesophageal echocardiographic (TEE) measure of systolic function. At this time not validated properly against acknowledged indices of systolic function.	Froml the end of operation until approx 4 hours after operation
Secondary	E/A Ratio (Unitless)	TEE ratio between early (E) transmitral flow and late (A) transmitral flow. An index of diastolic function althought not validated properly yet when measured from the oesophagus	At the end of operationon until approx 4 hours after operation
Secondary	Left Ventricular Rotation (Degrees)	TTE: Index of both systolic and diastolic function	96 hour after operation until 6 months after operation
Secondary	Mixed Venous Oxygenation (Per Cent)	Oxygen content (per cent of hemoglobin saturated) of venous blood in pulmonary artery	4 hours after operation until 21 hours after operation
Secondary	Lactate (mmol/l)	Arterial sampling of blood lactate	4 hours after operation until 21 hours after operation
Secondary	Troponin T (ug/l)	Blood sample expressing damage to the myocytes	4 hours after operation until 21 hours after operation
Secondary	Troponin T (ug/l)	Blood sample expressing damage to the myocytes	21 hours after operation until 96 hours after operation
Secondary	N-terminal Pro Brain Natriuretic Peptide (NT proBNP)(pg/ml)	blood sample reflecting stretch of the atrium/ventricle	4 hours after operation until 21 hours after operation
Secondary	N-terminal Pro Brain Natriuretic Peptide (NT proBNP)(pg/ml)	blood sample reflecting stretch of the atrium/ventricle	21 hours after operation until 96 hours after operation
Secondary	Systemic Arterial Pressure (mmHg)	Invasive measurements of arterial mean pressure	1 hour before operation until start of operation
Secondary	Systemic Arterial Pressure (mmHg)	Invasive measurements of arterial mean pressure	Start of operation until the end of operation, approximately 3 hours
Secondary	Systemic Arterial Pressure (mmHg)	Invasive measurements of arterial mean pressure	End of operation until approx 4 hours after operation
Secondary	Systemic Arterial Pressure (mmHg)	Invasive measurements of arterial mean pressure	4 hours after operation until 21 hours after operation
Secondary	Pulmonary Artery Pressures (mmHg)	Invasive measurement of mean pressure in the pulmonary artery	1 hour before operation until start of operation
Secondary	Pulmonary Artery Pressures (mmHg)	Invasive measurement of mean pressure in the pulmonary artery	Start of operation until end of operation, approximately 3 hours
Secondary	Pulmonary Artery Pressures (mmHg)	Invasive measurement of mean pressure in the pulmonary artery	End of operation until approx 4 hours after operation
Secondary	Pulmonary Artery Pressures (mmHg)	Invasive measurement of mean pressure in the pulmonary artery	4 hours after operation until 21 hours after operation
Secondary	Regional Longitudinal Strain (Unitless)	Index of systolic function derived from single transthoracic echocardiographic (TTE) projection	1 hour before start of operation until 21 hours after operation
Secondary	Regional Longitudinal Strain (Unitless)	Index of systolic function derived from single transthoracic echocardiographic (TTE) projection	21 hours after operation until 96 hours after operation
Secondary	Regional Longitudinal Strain (Unitless)	Index of systolic function derived from single transthoracic echocardiographic (TTE) projection	96 hours after operation until 6 months after operation
Secondary	Central Venous Pressure (mmHg)	Invasive measurement of pressure in the vena cava	1 hour before operation until start of operation
Secondary	Central Venous Pressure (mmHg)	Invasive measurement of pressure in the vena cava	Start of operation until end of operation, approximately 3 hours
Secondary	Central Venous Pressure (mmHg)	Invasive measurement of pressure in the vena cava	End of operation until approx 4 hours after operation
Secondary	Central Venous Pressure (mmHg)	Invasive measurement of pressure in the vena cava	4 hours after operation until 21 hours after operation
Secondary	Peak Systolic Velocity (m/s)	Tissue Doppler measure of systolic function	1 hour before operation until 21 hours after operation
Secondary	Peak Systolic Velocity (m/s)	Tissue Doppler measure of systolic function	21 hours after operation until 96 hours after operation
Secondary	Peak Systolic Velocity (m/s)	Tissue Doppler measure of systolic function	96 hours after operation until 6 months after operation
Secondary	Tricuspid Annular Plane Systolic Excursion (TAPSE) (mm)	Transthoracic echocardiographic measure of systolic function	1 hour before operation until 21 hours after operation
Secondary	Tricuspid Annular Plane Systolic Excursion (TAPSE) (mm)	Transthoracic echocardiographic measure of systolic function	21 hours after operation until 96 hours after operation
Secondary	Tricuspid Annular Plane Systolic Excursion (TAPSE) (mm)	Transthoracic echocardiographic measure of systolic function	96 hours after operation until 6 months after operation
Secondary	E/A-ratio (Unitless)	Transthoracic echocardiographic ratio between early (E) and late (A) transmitral blood velocities. Index of diastolic function.	1 hour before operation until 21 hours after operation
Secondary	E/A-ratio (Unitless)	Transthoracic echocardiographic ratio between early (E) and late (A) transmitral blood velocities. Index of diastolic function.	21 hours after operation until 96 hours after operation
Secondary	E/A-ratio (Unitless)	Transthoracic echocardiographic ratio between early (E) and late (A) transmitral blood velocities. Index of diastolic function.	96 hours after operation until 6 months after operation
Secondary	E'/A'-Ratio (Unitless)	Tissue Doppler transthoracic echocardiography: Ratio between tissue velocities at the mitral plan during early (E) diastole and late (A) diastole. Index of diastolic function.	1 hour before operation until 21 hours after roperation
Secondary	E'/A'-Ratio (Unitless)	Tissue Doppler transthoracic echocardiography: Ratio between tissue velocities at the mitral plan during early (E) diastole and late (A) diastole. Index of diastolic function.	21 hours after operation until 96 hours after operation
Secondary	E'/A'-Ratio (Unitless)	Tissue Doppler transthoracic echocardiography: Ratio between tissue velocities at the mitral plan during early (E) diastole and late (A) diastole. Index of diastolic function.	96 hours after operation until 6 months after operation
Secondary	Isovolumetric Relaxation Time (IVRT) (s)	Transthoracic measure of the time from aortic valve closure until mitral valve opening. A measure of diastolic function	1 hour before operation until 21 hours after operation
Secondary	Isovolumetric Relaxation Time (IVRT) (s)	Transthoracic measure of the time from aortic valve closure until mitral valve opening. A measure of diastolic function	21 hours after operation until 96 hours after operation
Secondary	Isovolumetric Relaxation Time (IVRT) (s)	Transthoracic measure of the time from aortic valve closure until mitral valve opening. A measure of diastolic function	96 hours after operation until 6 months after operation
Secondary	Ejection Fraction (Per Cent)	Transeosophageal echocardiography: Measure of systolic function	End of operation until approx. 4 hours after operation
Secondary	Isovolumetric Relaxation Time (IVRT) (s)	Transeosophageal echocardiography: Time from closure of aortic valve to opening of mitral valve. Measure of diastolic function.	End of operation until approx. 4 hours after operation
Secondary	Cardiac Index (l/Min/m2)	Invasive measurement measuring the cardiac output divided by calculated body surface area (DuBois formula)	1 hour before operation until start of operation
Secondary	Cardiac Index (l/Min/m2)	Invasive measurement measuring the cardiac output divided by calculated body surface area (DuBois formula)	Start of operation until end of operation, approximately 3 hours
Secondary	Cardiac Index (l/Min/m2)	Invasive measurement measuring the cardiac output divided by calculated body surface area (DuBois formula)	End of operation operation until approx. 4 hours after operation
Secondary	Cardiac Index (l/Min/m2)	Invasive measurement measuring the cardiac output divided by calculated body surface area (DuBois formula)	4 hours after operation until 21 hours after operation
Secondary	Inflammatory Parameters	Blood sample values of pro- and antiinflammatory mediators	4 hours before operation until 21 hours after operation
Secondary	Inflammatory Parameters	Blood sample values of pro- and antiinflammatory mediators	21 hours after operation until 96 hours after operation
Secondary	E/A-ratio (Transoesophageal)	Transoesophageal echocardiographic measure of diastolic heart function	from start of operation until end of operation, approximately 3 hours
Secondary	E/A-ratio (Transoesophageal)	Transoesophageal echocardiographic measure of diastolic heart function	from end of operation until approximately 4 hours after operation
Secondary	Urine Clearance	Urine analysis. Measure of kidney function.	from start of operation until 24 hours after operation