Using TEE to Evaluate the Effect of Levosimendan on Patients With ARDS Associated With RVD During MV

Using Transesophageal Echocardiography to Evaluate the Effect of Levosimendan on Patients With Acute Respiratory Distress Syndrome Associated With Right Ventricular Dysfunction During Mechanical Ventilation

Acute respiratory distress syndrome (ARDS) is often complicated by right ventricular dysfunction (RVD), Acute cor pulmonale is the most serious form of ARDS complicated with RVD.Levosimendan is indicated for short-term treatment of acute decompensated heart failure that is not responding well to conventional therapy and requires increased myocardial contractile force.In 2016, the European Society of Cardiology issued recommendations for the management of acute right heart failure, stating that levosimendan can improve right ventriculo-pulmonary artery coupling by both increasing right heart contractility and reducing pulmonary vascular resistance.However, the clinical application of levosimendan in the treatment of ARDS right heart dysfunction is insufficient.Therefore, this study intends to use transesophageal ultrasound to evaluate right ventricular function, reduce the limitation of poor right ventricular window in transthoracic echocardiography, and conduct a multi-center randomized controlled study to further explore the effects of levosimendan on right ventricular function in ARDS patients, such as tricuspid ring systolic displacement (TAPSE) and tricuspid ring systolic displacement velocity (S '). Effects of right ventricular area change fraction (RV FAC), right ventricular end-diastolic area/left ventricular end-diastolic area (RVEDA/LVEDA), pulmonary circulation resistance (PVR), hemodynamics and mortality.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Respiratory Distress Syndrome; Right Ventricular Dysfunction; Transesophageal Echocardiography
• Intervention / Treatment: Drug: levosimendan; Drug: 5% glucose injection

Detailed Description

Acute respiratory distress syndrome (ARDS) is often complicated by right ventricular dysfunction (RVD),the incidence can be as high as 64%, Acute cor pulmonale is the most serious form of ARDS complicated with RVD. The prognosis of ARDS patients with RVD is worse and the risk of death would be significantly increased.Currently, there are very limited clinical drug treatment options for RVD.Levosimendan is indicated for short-term treatment of acute decompensated heart failure that is not responding well to conventional therapy and requires increased myocardial contractile force.In 2016, the European Society of Cardiology issued recommendations for the management of acute right heart failure, stating that levosimendan can improve right ventriculo-pulmonary artery coupling by both increasing right heart contractility and reducing pulmonary vascular resistance. Levosimendan is therefore recommended to be given priority over dobutamine in the treatment of acute right heart failure.At present, there are also relevant clinical studies reporting that levosimendan can be used in acute right heart failure caused by different causes, including a single center randomized controlled study reporting that levosimendan can do work in the right ventricle of patients with sepsis ARDS, and has beneficial hemodynamic effects.However, the clinical application of levosimendan in the treatment of ARDS right heart dysfunction is insufficient.Therefore, this study intends to use transesophageal ultrasound to evaluate right ventricular function, reduce the limitation of poor right ventricular window in transthoracic echocardiography, and conduct a multi-center randomized controlled study to further explore the effects of levosimendan on right ventricular function in ARDS patients, such as tricuspid ring systolic displacement (TAPSE) and tricuspid ring systolic displacement velocity (S '). Effects of right ventricular area change fraction (RV FAC), right ventricular end-diastolic area/left ventricular end-diastolic area (RVEDA/LVEDA), pulmonary circulation resistance (PVR), RV-PA coupling, hemodynamics and mortality.

• Study Type: Interventional
• Enrollment (Anticipated): 58
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Yongran Wu, MD; Phone Number: 027-85351606; Email: 974528836@qq.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Yongran WU, master; Phone Number: 027-85351607 18627004016; Email: 974528836@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients who agree to participate in this clinical trial and sign informed consent
• Age 18-80 years old, gender unlimited
• Patients with ARDS(According to the diagnostic criteria of ARDS in Berlin 2012) requiring mechanical ventilation; Acute right ventricular dysfunction due to ARDS

Exclusion Criteria:

• Pregnant or lactating women;
• Chronic cardiac insufficiency, pulmonary hypertension and/or right ventricular enlargement caused by chronic cardiopulmonary disease, cardiogenic shock or after major cardiac surgery before ARDS;
• right ventricular myocardial infarction;
• Uncorrected hypotension, hypoxemia and hypercapnia, or acid-base balance disturbance
• Mechanical ventilation driving pressure >=18cmH2O before randomization
• Rapid arrhythmia;
• pericardial tamponade;
• Pulmonary embolism;
• severe renal insufficiency;
• severe liver insufficiency;
• Failure to sign informed consent;
• known allergy to the test drug and control drug;
• Patients who have participated in other clinical trials within 30 days

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: treatment group A; intravenously injected levosimendan 12.5mg with 5% glucose injection 50ml configuration at 2ml/h for 24h	Drug: levosimendan; Levosimendan 12.5mg was injected intravenously in a 5% glucose injection 50ml configuration at a rate of 2ml/h for 24 hours.The injection was performed at a constant rate of 2ml/h. If there was no significant hypotension or tachycardia, the injection was completed within 24h
Placebo Comparator: treatment group B; treatment group B: control group with 5% glucose injection 2ml/h for 24h	Drug: 5% glucose injection; 5% glucose injection 50ml configuration at a rate of 2ml/h for 24 hours.The injection was performed at a constant rate of 2ml/h. If there was no significant hypotension or tachycardia, the injection was completed within 24h

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of right ventricular dysfunction occurrence within 48 hours after randomization.	Right ventricular dysfunction(RVD) is diagnosed when the results of an echocardiogram show one of the following, including: tricuspid annular plane systolic excursion(TAPSE)<16 mm, right ventricular fractional area change(RV FAC)<35% or systolic velocity of the lateral tricuspid valve annulus( RV S')<10 cm/s.	From the time point of enrollment to 48 hours after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
28-day mortality	28-day mortality after study entry	Day 28 after study entry
in-hospital mortality	Any death occurred during hospitalization(up to 90 days)	From the day patients admitted to hospital to the day death or discharge(up to 90 days)
Right ventricular area fractional change (RV FAC) 48 hours after randomization	Right ventricular area fractional change (RV FAC)is a simple and repeatable ultrasound method for evaluating RV function. Methods: The RV end-diastolic area (RVEDA) and RV end-systolic area (RVESA) were measured on the apical four-chamber section by two-dimensional ultrasound. RV FAC=(RVEDA- RVESA)/RVEDA*100%.	at the time of 48 hours after enrollment
tricuspid annular plane systolic excursion(TAPSE) 48 hours after randomization	TAPSE is one of the most effective ultrasound methods for evaluating right ventricular function.Measurement method: TAPSE was measured on the four-chamber section of the apex of the heart by M-mode ultrasound. the sampling line was placed at the side wall of the tricuspid valve ring, parallel to the free wall of the right ventricle as far as possible, and the displacement of the tricuspid valve ring was measured from the end of diastole to the end of systole.	at the time of 48 hours after enrollment
Tricuspid annular systolic S' velocity (TS')	TS' is an objective and accurate ultrasound technique for evaluating right ventricular function.Measurement method:The sample volume was applied to the free wall of the RV and the peak velocity of tricuspid annulus motion was measured in the four-chamber section of the apex by tissue doppler imaging (TDI)	at the time of 48 hours after enrollment
Right ventricular end-diastolic area/left ventricular end-diastolic area (RVEDA/LVEDA)	RVEDA/LVEDA a simple and repeatable ultrasound method for evaluating dynamics changes of RV function.Methods: The RV end-diastolic area (RVEDA) and left ventricular(LV) end-systolic area (LVEDA) were measured on the apical four-chamber section by two-dimensional ultrasound	at the time of 48 hours after enrollment
Pulmonary circulatory resistance (PVR)	Increased PVR can lead to deterioration of RV function.Pulse Doppler imaging (PWD) was used to obtain the pulmonary artery flow spectrum from the pulmonic valve on the short axial section of the parasternal great vessels.	at the time of 48 hours after enrollment
Sequential Organ Failure Assessment score	The higher the Sequential Organ Failure Assessment(SOFA) score, the higher the disease risk factor and the higher the mortality rate(The highest score is 24, while the lowest score is 0).	at the time of 48 hours after enrollment
cardiac index(CI) patients	CI is an important parameter to reflect the cardiac function of	at the time of 48 hours after enrollment
Central venous oxygen saturation(ScvO2)	The patient's blood was collected through a central venous catheter for blood gas analysis to calculate SCVO2 to indicate tissue perfusion	at the time of 48 hours after enrollment
systemic vascular resistance(SVR)	Peripheral vascular resistance is an important indicator of hemodynamics. It is not only a parameter reflecting cardiac afterload, but also a quantitative indicator reflecting the degree of patency of cerebrovascular microcirculation.	at the time of 48 hours after enrollment
Mean arterial pressure (MAP)	MAP represents peripheral organ perfusion pressure.	at the time of 48 hours after enrollment
Central venous pressure(CVP)	CVP is the pressure of the upper and lower vena cava entering the right atrium, measured by the upper and lower vena cava or the internal tube of the right atrium, which reflects the pressure of the right atrium, and is one of the main indicators for clinical observation of hemodynamics	at the time of 48 hours after enrollment
systemic vascular resistance index(SVRI)	SVRI=80*(MAP-CVP)/CI	at the time of 48 hours after enrollment

Collaborators and Investigators

• Sponsor: Wuhan Union Hospital, China

Study record dates

Study Major Dates

• Study Start (Anticipated): March 22, 2023
• Primary Completion (Anticipated): December 1, 2025
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: February 18, 2023
• First Submitted That Met QC Criteria: March 12, 2023
• First Posted (Actual): March 14, 2023

Study Record Updates

• Last Update Posted (Actual): March 14, 2023
• Last Update Submitted That Met QC Criteria: March 12, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Ventricular Dysfunction; Ventricular Dysfunction, Right; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Protective Agents; Cardiotonic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Simendan
• Other Study ID Numbers: ARVD20220810

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No