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

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

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

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 Summary:

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.


Sponsor: University of Aarhus

Current Primary Outcome: E/E'(unitless) [ Time Frame: 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


Original Primary Outcome:

  • Global Strain (unitless) [ Time Frame: 20 hours before operation until1 hour before operation ]
    Echocardiographic index of systolic function of especially longitudinally oriented myofilaments
  • E/E'(unitless) [ Time Frame: 20 hours before operation until 1 hour before operation ]
    Ration between early transmitral flow (E) and mitral annular tissue velocity(E'). This ratio is an echocardiographic index of diastolic function
  • Global Strain (unitless) [ Time Frame: 1 hour before operation until approx. 21 hours after operation ]
    Echocardiographic index of systolic function of especially longitudinally oriented myofilaments
  • E/E'(unitless) [ Time Frame: 1 hour before operation until about 21 hours after operation ]
    Ration between early transmitral flow (E) and mitral annular tissue velocity(E'). This ratio is an echocardiographic index of diastolic function


Current Secondary Outcome:

  • Ejection fraction (per cent) [ Time Frame: 4 hours before until 1 hour before start of operation ]
    TTE: Index of systolic function
  • Peak systolic velocity (m/s) [ Time Frame: 4 hours before operation until 1 hour before operation ]
    Tissue Doppler measure of systolic function
  • Tricuspid annular plane systolic excursion (TAPSE) (mm) [ Time Frame: 4 hours before operation until 1 hour before operation ]
    Transthoracic echocardiographic measure of systolic function
  • E/A-ratio (unitless) [ Time Frame: 4 hours before operation until 1 hour before operation ]
    Transthoracic echocardiographic ratio between early (E) and late (A) transmitral blood velocities. Index of diastolic function.
  • E'/A'-ratio (unitless) [ Time Frame: 4 hours before operation until 1 hour before 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.
  • Isovolumetric relaxation time (IVRT) (s) [ Time Frame: 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
  • Ejection fraction (per cent) [ Time Frame: At start of operation until end of operation, approximately 3 hours ]
    Transeosophageal echocardiography: Measure of systolic function
  • Cardiac index (l/min/m2) [ Time Frame: 4 hours before operation until 1 hour before operation ]
    Invasive measurement measuring the cardiac output divided by calculated body surface area (DuBois formula)
  • Central venous pressure (mmHg) [ Time Frame: 4 hours before operation until 1 hours before operation ]
    Invasive measurement of pressure in the vena cava
  • Pulmonary artery pressures (mmHg) [ Time Frame: 4 hours before operation until 1 hour before operation ]
    Invasive measurement of mean pressure in the pulmonary artery
  • Systemic arterial pressure (mmHg) [ Time Frame: 4 hours before operation until 1 hour before operation ]
    Invasive measurements of arterial mean pressure
  • N-terminal pro Brain natriuretic peptide (NT proBNP)(pg/ml) [ Time Frame: 4 hours before operation until 4 hours after operation ]
    blood sample reflecting stretch of the atrium/ventricle
  • Troponin T (ug/l) [ Time Frame: 4 hours before operation until 4 hours after operation ]
    Blood sample expressing damage to the myocytes
  • lactate (mmol/l) [ Time Frame: 4 hours before operation until 4 hour after operation ]
    Arterial sampling of blood lactate
  • Mixed venous oxygenation (per cent) [ Time Frame: 4 hours before operation until 4 hour after operation ]
    Oxygen content (per cent of hemoglobin saturated) of venous blood in pulmonary artery
  • E/A ratio (unitless) [ Time Frame: 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
  • Regional longitudinal strain (unitless) [ Time Frame: 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.
  • Need for conventional inotropical agents [ Time Frame: From start of operation until 5 days after operation ]
    Conventional inotropics are comprised of all inotropics acting primarily through alfa- or beta- stimulation.
  • Intravenous fluid requirement (l) [ Time Frame: Within 24 hours from start of operation ]
    Total volume of intravenous fluid required including blood products.
  • Operation time (minutes) [ Time Frame: From "knife start" until "knife end", approximately 3 hours ]
  • Time on heart-lung machine (minutes) [ Time Frame: From time of cardioplegia until selfsufficient cardiac action, ap

    Original Secondary Outcome:

    • Circumferential strain (unitless) [ Time Frame: 20 hours before until 1 hour before start of operation ]
      Transthoracic echocardiographic (TTE) measure of systolic function
    • Ejection fraction (per cent) [ Time Frame: 20 hours before until 1 hour before start of operation ]
      TTE: Index of systolic function
    • Peak systolic velocity (m/s) [ Time Frame: 20 hours before operation until 1 hour before operation ]
      Tissue Doppler measure of systolic function
    • Tricuspid annular plane systolic excursion (TAPSE) (mm) [ Time Frame: 20 hours before operation until 1 hour before operation ]
      Transthoracic echocardiographic measure of systolic function
    • E/A-ratio (unitless) [ Time Frame: 20 hours before operation until 1 hour before operation ]
      Transthoracic echocardiographic ratio between early (E) and late (A) transmitral blood velocities. Index of diastolic function.
    • E'/A'-ratio (unitless) [ Time Frame: 20 hours before operation until 1 hour before 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.
    • Isovolumetric relaxation time (IVRT) (s) [ Time Frame: 20 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
    • Ejection fraction (per cent) [ Time Frame: At start of operation until end of operation, approximately 3 hours ]
      Transeosophageal echocardiography: Measure of systolic function
    • Isovolumetric relaxation time (IVRT) (s) [ Time Frame: At the start of operation until the end of operation, approximately 3 hours ]
      Transeosophageal echocardiography: Time from closure of aortic valve to opening of mitral valve. Measure of diastolic function.
    • Cardiac index (l/min/m2) [ Time Frame: 20 hours before operation until 1 hour before operation ]
      Invasive measurement measuring the cardiac output divided by calculated body surface area (DuBois formula)
    • Central venous pressure (mmHg) [ Time Frame: 20 hours before operation until 1 hours before operation ]
      Invasive measurement of pressure in the vena cava
    • Pulmonary artery pressures (mmHg) [ Time Frame: 20 hours before operation until 1 hour before operation ]
      Invasive measurement of mean pressure in the pulmonary artery
    • Systemic arterial pressure (mmHg) [ Time Frame: 20 hours before operation until 1 hour before operation ]
      Invasive measurements of arterial mean pressure
    • N-terminal pro Brain natriuretic peptide (NT proBNP)(pg/ml) [ Time Frame: 20 hours before operation until 1 hour before operation ]
      blood sample reflecting stretch of the atrium/ventricle
    • Troponin T (ug/l) [ Time Frame: 20 hours before operation until 1 hour before operation ]
      Blood sample expressing damage to the myocytes
    • lactate (mmol/l) [ Time Frame: 20 hours before operation until 1 hour before operation ]
      Arterial sampling of blood lactate
    • Mixed venous oxygenation (per cent) [ Time Frame: 20 hours before operation until 1 hour before operation ]
      Oxygen content (per cent of hemoglobin saturated) of venous blood in pulmonary artery
    • Left ventricular rotation (degrees) [ Time Frame: 20 hours before operation until 1 hour before operation ]
      TTE: Index of both systolic and diastolic function
    • E/A ratio (unitless) [ Time Frame: 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
    • Regional longitudinal strain (unitless) [ Time Frame: 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.
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      Information By: University of Aarhus

      Dates:
      Date Received: August 10, 2010
      Date Started: September 2010
      Date Completion: March 2013
      Last Updated: August 3, 2012
      Last Verified: August 2012