The purpose of this study is to assess whether circulating Angiotensin (Ang) II and Ang (1-7) levels are associated with right ventricular (RV) dysfunction in mechanically ventilated subjects. It is also designed to further characterize the subject population for severity of RV dysfunction. This study will investigate the association of renin-angiotensin system (RAS) peptides and markers of RV function, as measured by echocardiography, in subjects requiring acute mechanical ventilation. Maximum 150 subjects will be enrolled for the study and they will be evaluated over three days period using standard of care investigations, including trans-thoracic echocardiography (TTE) and/or trans-esophageal echocardiography (TOE) echocardiography. The maximum total duration of this study for subjects is 28 days.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
57
Local standard of care will include fluid resuscitation, use of vasopressor drugs and renal support.
Mechanical ventilation will be based on volume-assist control mode, with a target tidal volume of 6-8 milliliter per kg (mL/kg) and a target plateau pressure of 30 centimeter of water (cmH2O).
GSK Investigational Site
Boulogne-Billancourt, France
GSK Investigational Site
Créteil, France
Renin-angiotensin System Cascade Biomarker to Include Angiotensin (Ang) II Level
Blood samples were collected for renin-angiotensin system biomarkers at indicated time points. Evaluable Population consisted of all participants for whom pulmonary arterial systolic pressure (PASP), ratio of right ventricular to left ventricular end-diastolic area (RV size ratio), Ang II and Ang(1-7) data have been recorded for at least one study time point, and who did not retrospectively withdraw the consent.
Time frame: Days 1, 2 and 3
Ratio of RV to Left Ventricular (LV) End-diastolic Area (RV Size Ratio)
Right ventricular size ratio was measured using TTE or TOE.
Time frame: Days 1, 2 and 3
Number of Participants With Paradoxical Septal Motion
Paradoxical septal motion is the systolic movement of the interventricular septum toward the RV despite normal thickening. Paradoxical septal motion was measured by TTE or TOE. Number of participants who had paradoxical septal motion have been reported.
Time frame: Days 1, 2 and 3
Pulmonary Arterial Systolic Pressure at Indicated Time Points
Pulmonary arterial systolic pressure was measured using TTE or TOE.
Time frame: Days 1, 2 and 3
Right Atrial Pressure at Indicated Time Points
Right atrial pressure is the blood pressure in the right atrium of the heart. Right atrial pressure was measured by TTE or TOE.
Time frame: Days 1, 2 and 3
Inferior Vena Cava Diameter at End Expiration at Indicated Time Points
Inferior vena cava diameter was measured using TTE or TOE. Pulmonary arterial systolic pressure was estimated from trans-tricuspid pressure and right atrial pressure or inferior vena cava diameter.
Time frame: Days 1, 2 and 3
Pearson Correlation Coefficient Between PASP and Ang II Level
Pearson correlation coefficient between PASP and Ang II level was derived using all available data from participants in the evaluable population. Pearson's correlation coefficient is a measure of the linear dependence between 2 variables. A correlation of +1 or -1 may occur if the data from the 2 variables lie exactly on a line. Pearson's correlation coefficient was calculated using Statistical Analysis Software (SAS).
Time frame: Up to Day 3
Pearson Correlation Coefficient Between RV Size Ratio and Ang II Level
Pearson correlation coefficient between RV size ratio and Ang II level was derived using all available data from participants in the evaluable population. Pearson's correlation coefficient is a measure of the linear dependence between 2 variables. A correlation of +1 or -1 may occur if the data from the 2 variables lie exactly on a line. Pearson's correlation coefficient was calculated using SAS.
Time frame: Up to Day 3
Number of Participants With Pulmonary Circulatory Dysfunction
Pulmonary circulatory dysfunction is defined as moderate dysfunction (pulmonary arterial systolic pressure \[\>40 millimeters of mercury\] or a dilated RV end diastolic RV/left ventricle \[LV\] area ratio \[\>=0.6\] but without septal dyskinesia). At risk Population consisted of participants who satisfied following criteria: 1. pulmonary arterial systolic pressure and ratio of RV to LV end-diastolic area recorded for all three study days \[regardless of the Ang II and Ang(1-7) status\] and/or; 2. databased acute cor pulmonale/pulmonary circulatory dysfunction and/or acute respiratory distress syndrome (ARDS) assessment during the study period (even if they do not have three days worth of study assessments for the echo outcomes) were evaluated for acute cor pulmonale/pulmonary circulatory dysfunction and ARDS incidence rates. Number of participants with Pulmonary Circulatory Dysfunction have been reported.
Time frame: Days 1, 2 and 3
Number of Participants With Acute Cor Pulmonale
Acute cor pulmonale is defined as a dilated RV in the mid-esophagus longitudinal view or apical 4-chamber view (end-diastolic RV/LV area ratio \[0.6\]) associated with the presence of a septal dyskinesia in the (transgastric) short-axis view of the heart. Number of participants with acute cor pulmonale have been reported.
Time frame: Days 1, 2 and 3
Number of Participants With Severe Acute Cor Pulmonale
Severe acute cor pulmonale is defined as severely dilated RV (end-diastolic RV/LV area ratio \>=1) with septal dyskinesia. Number of participants with severe acute cor pulmonale have been reported.
Time frame: Days 1, 2 and 3
Renin-angiotensin System Cascade Biomarker: Ang(1-7) Level
Blood samples were collected for renin-angiotensin system biomarkers at indicated time points.
Time frame: Days 1, 2 and 3
Renin-angiotensin System Cascade Biomarker: Ang II/ Ang(1-7) Ratio
Blood samples were collected for renin-angiotensin system biomarkers at indicated time points.
Time frame: Days 1, 2 and 3
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Pearson Correlation Coefficient Between PASP and Ang(1-7)
Pearson correlation coefficient between PASP and Ang(1-7) was derived using all available data from participants in the evaluable population. Pearson's correlation coefficient is a measure of the linear dependence between 2 variables. A correlation of +1 or -1 may occur if the data from the 2 variables lie exactly on a line. Pearson's correlation coefficient was calculated using SAS.
Time frame: Up to Day 3
Pearson Correlation Coefficient Between PASP and Ang II/Ang(1-7)
Pearson correlation coefficient between PASP and Ang II/Ang(1-7) was derived using all available data from participants in the evaluable population. Pearson's correlation coefficient is a measure of the linear dependence between 2 variables. A correlation of +1 or -1 may occur if the data from the 2 variables lie exactly on a line. Pearson's correlation coefficient was calculated using SAS.
Time frame: Up to Day 3
Pearson Correlation Coefficient Between RV Size Ratio and Ang(1-7)
Pearson correlation coefficient between RV size ratio and Ang(1-7) was derived using all available data from participants in the evaluable population. Pearson's correlation coefficient is a measure of the linear dependence between 2 variables. A correlation of +1 or -1 may occur if the data from the 2 variables lie exactly on a line. Pearson's correlation coefficient was calculated using SAS.
Time frame: Up to Day 3
Pearson Correlation Coefficient Between RV Size Ratio and Ang II/Ang(1-7)
Pearson correlation coefficient between RV size ratio and Ang II/Ang(1-7) was derived using all available data from participants in the evaluable population. Pearson's correlation coefficient is a measure of the linear dependence between 2 variables. A correlation of +1 or -1 may occur if the data from the 2 variables lie exactly on a line. Pearson's correlation coefficient was calculated using SAS.
Time frame: Up to Day 3