Effects of Levosimendan, Milrinone and Norepinephrine on Left and Right Ventricular Function in Septic Shock (SCLM)

Potential Differences Between Levosimendan and Milrinone on Myocardial and Hemodynamic Variables in Patients With Septic Cardiomyopathy. Effects of Norepinephrine on Right Ventricular Function in Patient With Septic Shock.

The aim of this study is to investigate the effects milrinon and levosimandan on n heart function in septic cardiomyopathy and how norepinephrine affects the left and right ventricular function in patients with septick shock using pulmonary artery catheter, conventional and strain echocardiography.

Study Overview

• Status: Unknown
• Conditions: Septic Shock; Cardiomyopathy
• Intervention / Treatment: Drug: Norepinephrine; Drug: Milrinone; Drug: Levosimendan

Detailed Description

This is a prospective study where 30 patients with septic chock during the care in ICU, will be included. Patients with a history of previous heart disease are excluded from the study. Each patient is in need of norepinephrine infusion and on mechanical ventilation. Initially the mean arterial pressure (MAP) is randomly changed from 60 to 75 and then to 90 mmHg. Hemodynamic variables as blood pressure, cardiac output, pulmonary artery occlusion pressure (PAOP) will be registerd at each MAP-level, arterial line and pulmonary artery catheter (PAC) and the cardiac function will be assessed with conventional and strain echocardiography. Then, if the echocardiogram shows impaired LV-function will the patient be randomized to receive either Milrinone or Levosimendan. Hemodynamic variables as blood pressure, cardiac output, pulmonary artery occlusion pressure (PAOP) will be registered again, as well the cardiac function with conventional and strain echocardiography. Echocardiograms will be analysed for the determination of LV an RV strain. Potential differences between different levels of blood pressure as well as effects of Milrinone or Levosimendan on hemodynamic and echocardiographyc variables will be analysed.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• Sweden
  • Västra Götaland
    • Gothenburg, Västra Götaland, Sweden, 41345
      • Central intensivvårdsavdelning Sahlgrenska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Septic shock.
• All patients will be resuscitated with fluids before the inclusion.
• Need of Norepinephrine infusion.
• Myocardial dysfunction in echocardiogram, either LVEF < 50% or Global Left Ventricular Systolic strain over -15%.

Exclusion Criteria:

• History of previous heart disease or pulmonary hypertension.
• Age < 18 years.
• Cardiac arrhythmia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Norepinephrine; Doser	Drug: Norepinephrine; Norepinephrine will be given to the patient due to septic shock. After the inclusion we will change the dose of Norepinephrine to achieve 3 different MAP-levels, 60 mmHg, 75 mmHg and 90 mmHg.
Active Comparator: Milrinone; Doser	Drug: Milrinone; Corotrope will be given and after 30 minutes of treatment the cardiac function will be assessed with echocardiography and systemic hemodynamics.; Other Names: Corotrope
Active Comparator: Levosimendan; Doser	Drug: Levosimendan; Levosimendan will be given and after 30 minutes of treatment the cardiac function will be assessed with echocardiography and systemic hemodynamics.; Other Names: Simdax

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in LV systolic strain	Changes in LV systolic function (global strain) will be assessed by 2D speckle tracking echocardiography	1.5 hours
Changes in RV systolic strain	Changes in RV systolic function (RV free wall strain) will be assessed by 2D speckle tracking echocardiography	1.5 hours

Collaborators and Investigators

• Sponsor: Sahlgrenska University Hospital, Sweden
• Investigators: Study Chair: Sven-Erik Ricksten, Professor, Sahlgrenska Academy, dep of clinical science

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Anticipated): January 1, 2019
• Study Completion (Anticipated): January 1, 2019

Study Registration Dates

• First Submitted: December 6, 2015
• First Submitted That Met QC Criteria: December 22, 2015
• First Posted (Estimate): December 29, 2015

Study Record Updates

• Last Update Posted (Actual): November 29, 2018
• Last Update Submitted That Met QC Criteria: November 27, 2018
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Norepinephrine; Levosimendan; Milrinone; Myocardial strain; Septic cardiomyopathy
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock; Cardiomyopathies; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Phosphodiesterase Inhibitors; Sympathomimetics; Vasoconstrictor Agents; Phosphodiesterase 3 Inhibitors; Norepinephrine; Simendan; Milrinone
• Other Study ID Numbers: K050711

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No