Trial Outcomes & Findings for Effects of Levosimendan in Patients Eligible for Aortic Valve Replacement With Left Ventricular Hypertrophy (NCT NCT01188369)

Results Overview

Ration between early transmitral flow (E) and mitral annular tissue velocity(E'). This ratio is an echocardiographic index of diastolic function

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

20 participants

Primary outcome timeframe

4 hours before operation until 21 hour after operation

Results posted on

2018-12-03

Participant Flow

Participant milestones

Participant milestones
Measure	Levosimendan infusion 0,1ug/kg/min for duration of ca. 4 hours prior to operation and until the end of operation levosimendan: Intravenous infusion, 0,1ug/kg/min, duration 4 hours prior to operation and until the end of operation.	Placebo Identical placebo placebo drug: Intravenous infusion, colour identical to levosimendan
Overall Study STARTED	10	10
Overall Study COMPLETED	10	10
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Levosimendan n=10 Participants infusion 0,1ug/kg/min for duration of ca. 4 hours prior to operation and until the end of operation levosimendan: Intravenous infusion, 0,1ug/kg/min, duration 4 hours prior to operation and until the end of operation.	Placebo n=10 Participants Identical placebo placebo drug: Intravenous infusion, colour identical to levosimendan	Total n=20 Participants Total of all reporting groups
Age, Continuous	76 years n=5 Participants	73 years n=7 Participants	74 years n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants
Region of Enrollment Denmark	10 participants n=5 Participants	10 participants n=7 Participants	10 participants n=5 Participants

PRIMARY outcome

Timeframe: 4 hours before operation until 21 hour after operation

Ration between early transmitral flow (E) and mitral annular tissue velocity(E'). This ratio is an echocardiographic index of diastolic function

Outcome measures

Outcome measures
Measure	Levosimendan n=10 Participants infusion 0,1ug/kg/min for duration of ca. 4 hours prior to operation and until the end of operation levosimendan: Intravenous infusion, 0,1ug/kg/min, duration 4 hours prior to operation and until the end of operation.	Placebo n=10 Participants Identical placebo placebo drug: Intravenous infusion, colour identical to levosimendan
E/E'(Unitless)	12.6 Unitless Interval 8.9 to 24.6	13.7 Unitless Interval 8.4 to 28.1

SECONDARY outcome

Timeframe: 4 hours before surgery until 1 hour before operation

Transthoracic measure of the time from aortic valve closure until mitral valve opening. A measure of diastolic function

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At start of operation until end of operation, approximately 3 hours

Transeosophageal echocardiography: Measure of systolic function

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 hours before operation until 1 hour before operation

Invasive measurement measuring the cardiac output divided by calculated body surface area (DuBois formula)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 hours before operation until 1 hours before operation

Invasive measurement of pressure in the vena cava

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 hours before operation until 1 hour before operation

Invasive measurement of mean pressure in the pulmonary artery

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 hours before operation until 1 hour before operation

Invasive measurements of arterial mean pressure

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 hours before operation until 4 hours after operation

blood sample reflecting stretch of the atrium/ventricle

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 hours before operation until 4 hours after operation

Blood sample expressing damage to the myocytes

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 hours before operation until 4 hour after operation

Arterial sampling of blood lactate

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 hours before operation until 4 hour after operation

Oxygen content (per cent of hemoglobin saturated) of venous blood in pulmonary artery

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At the start of operation until the end of operationon, approximately 3 hours

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At the start of operation until the end of operation, approximately 3 hours

Transoesophageal echocardiographic (TEE) measure of systolic function. At this time not validated properly against acknowledged indices of systolic function.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From start of operation until 5 days after operation

Conventional inotropics are comprised of all inotropics acting primarily through alfa- or beta- stimulation.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Within 24 hours from start of operation

Total volume of intravenous fluid required including blood products.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From "knife start" until "knife end", approximately 3 hours

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From time of cardioplegia until selfsufficient cardiac action, approximately 1 hour

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From intubation until extubation, approximately 6 hours

Total time intubated including time of operation and in the intensive care ward

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From admission to the intensive care unit until discharge from intensive care unit, approximately 24 hours

Total admission time in the intensive care after operation

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: -4 hours until + 96 hours with respect to start of operation

Development of Ventricular tachycardia

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: -4 hours until + 96 hours with respect to start of operation

Development of atrial flutter/fibrillation

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 hours before operaton until 1 hour before operaton

Need for norepinephrine as an antagonist to the vasodilatatory effect of levosimendan

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 hours before operation until 1 hour before operation

Occurence of nausea

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 hours before operation until approximately 1 hour before operation

Occurence of headache

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 hours before until 1 hour before start of operation

Index of systolic function derived from single transthoracic echocardiographic (TTE) projection

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 hour before until 21 hour after start of operation

TTE: Index of systolic function

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 21 hours after operation until 96 hours after start of operation

TTE: Index of systolic function

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 96 hours after operation until 6 months after operation

TTE: Index of systolic function

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Froml the end of operation until approx 4 hours after operation

Transoesophageal echocardiographic (TEE) measure of systolic function. At this time not validated properly against acknowledged indices of systolic function.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At the end of operationon until approx 4 hours after operation

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 96 hour after operation until 6 months after operation

TTE: Index of both systolic and diastolic function

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 hours after operation until 21 hours after operation

Oxygen content (per cent of hemoglobin saturated) of venous blood in pulmonary artery

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 hours after operation until 21 hours after operation

Arterial sampling of blood lactate

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 hours after operation until 21 hours after operation

Blood sample expressing damage to the myocytes

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 21 hours after operation until 96 hours after operation

Blood sample expressing damage to the myocytes

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 hours after operation until 21 hours after operation

blood sample reflecting stretch of the atrium/ventricle

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 21 hours after operation until 96 hours after operation

blood sample reflecting stretch of the atrium/ventricle

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 hour before operation until start of operation

Invasive measurements of arterial mean pressure

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Start of operation until the end of operation, approximately 3 hours

Invasive measurements of arterial mean pressure

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: End of operation until approx 4 hours after operation

Invasive measurements of arterial mean pressure

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 hours after operation until 21 hours after operation

Invasive measurements of arterial mean pressure

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 hour before operation until start of operation

Invasive measurement of mean pressure in the pulmonary artery

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Start of operation until end of operation, approximately 3 hours

Invasive measurement of mean pressure in the pulmonary artery

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: End of operation until approx 4 hours after operation

Invasive measurement of mean pressure in the pulmonary artery

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 hours after operation until 21 hours after operation

Invasive measurement of mean pressure in the pulmonary artery

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 hour before start of operation until 21 hours after operation

Index of systolic function derived from single transthoracic echocardiographic (TTE) projection

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 21 hours after operation until 96 hours after operation

Index of systolic function derived from single transthoracic echocardiographic (TTE) projection

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 96 hours after operation until 6 months after operation

Index of systolic function derived from single transthoracic echocardiographic (TTE) projection

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 hour before operation until start of operation

Invasive measurement of pressure in the vena cava

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Start of operation until end of operation, approximately 3 hours

Invasive measurement of pressure in the vena cava

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: End of operation until approx 4 hours after operation

Invasive measurement of pressure in the vena cava

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 hours after operation until 21 hours after operation

Invasive measurement of pressure in the vena cava

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 hour before operation until 21 hours after operation

Tissue Doppler measure of systolic function

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 21 hours after operation until 96 hours after operation

Tissue Doppler measure of systolic function

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 96 hours after operation until 6 months after operation

Tissue Doppler measure of systolic function

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 hour before operation until 21 hours after operation

Transthoracic echocardiographic measure of systolic function

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 21 hours after operation until 96 hours after operation

Transthoracic echocardiographic measure of systolic function

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 96 hours after operation until 6 months after operation

Transthoracic echocardiographic measure of systolic function

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 hour before operation until 21 hours after operation

Transthoracic echocardiographic ratio between early (E) and late (A) transmitral blood velocities. Index of diastolic function.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 21 hours after operation until 96 hours after operation

Transthoracic echocardiographic ratio between early (E) and late (A) transmitral blood velocities. Index of diastolic function.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 96 hours after operation until 6 months after operation

Transthoracic echocardiographic ratio between early (E) and late (A) transmitral blood velocities. Index of diastolic function.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 hour before operation until 21 hours after roperation

Tissue Doppler transthoracic echocardiography: Ratio between tissue velocities at the mitral plan during early (E) diastole and late (A) diastole. Index of diastolic function.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 21 hours after operation until 96 hours after operation

Tissue Doppler transthoracic echocardiography: Ratio between tissue velocities at the mitral plan during early (E) diastole and late (A) diastole. Index of diastolic function.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 96 hours after operation until 6 months after operation

Tissue Doppler transthoracic echocardiography: Ratio between tissue velocities at the mitral plan during early (E) diastole and late (A) diastole. Index of diastolic function.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 hour before operation until 21 hours after operation

Transthoracic measure of the time from aortic valve closure until mitral valve opening. A measure of diastolic function

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 21 hours after operation until 96 hours after operation

Transthoracic measure of the time from aortic valve closure until mitral valve opening. A measure of diastolic function

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 96 hours after operation until 6 months after operation

Transthoracic measure of the time from aortic valve closure until mitral valve opening. A measure of diastolic function

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: End of operation until approx. 4 hours after operation

Transeosophageal echocardiography: Measure of systolic function

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: End of operation until approx. 4 hours after operation

Transeosophageal echocardiography: Time from closure of aortic valve to opening of mitral valve. Measure of diastolic function.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 hour before operation until start of operation

Invasive measurement measuring the cardiac output divided by calculated body surface area (DuBois formula)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Start of operation until end of operation, approximately 3 hours

Invasive measurement measuring the cardiac output divided by calculated body surface area (DuBois formula)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: End of operation operation until approx. 4 hours after operation

Invasive measurement measuring the cardiac output divided by calculated body surface area (DuBois formula)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 hours after operation until 21 hours after operation

Invasive measurement measuring the cardiac output divided by calculated body surface area (DuBois formula)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 hours before operation until 21 hours after operation

Blood sample values of pro- and antiinflammatory mediators

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 21 hours after operation until 96 hours after operation

Blood sample values of pro- and antiinflammatory mediators

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from start of operation until end of operation, approximately 3 hours

Transoesophageal echocardiographic measure of diastolic heart function

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from end of operation until approximately 4 hours after operation

Transoesophageal echocardiographic measure of diastolic heart function

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from start of operation until 24 hours after operation

Urine analysis. Measure of kidney function.

Outcome measures

Outcome data not reported

Adverse Events

Levosimendan

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Levosimendan n=10 participants at risk infusion 0,1ug/kg/min for duration of ca. 4 hours prior to operation and until the end of operation levosimendan: Intravenous infusion, 0,1ug/kg/min, duration 4 hours prior to operation and until the end of operation.	Placebo n=10 participants at risk Identical placebo placebo drug: Intravenous infusion, colour identical to levosimendan
Cardiac disorders Postoperative atrial fibrillation	90.0% 9/10 • Number of events 10	60.0% 6/10 • Number of events 10

Additional Information

Dr. Peter Juhl-Olsen

Aarhus University Hospital

Phone: +4578451199

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place