Trial Outcomes & Findings for Study of Renin-angiotensin System in Mechanically Ventilated Subjects (NCT NCT03212690)
NCT ID: NCT03212690
Last Updated: 2020-04-01
Results Overview
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.
TERMINATED
NA
57 participants
Days 1, 2 and 3
2020-04-01
Participant Flow
This study elucidated the association of the Renin-angiotensin system and right ventricular (RV) function in mechanically ventilated participants. This study was conducted at two centers in France from 11-June-2018 to 08-July-2019. A total of 57 participants were enrolled in this study.
The study was terminated as overall probability of project success was considered low. The study had significant programmatic risks identified with development plan for Recombinant Human Angiotensin Converting Enzyme2 in critical care including participant identification, uncertainty around potential to impact mortality and operational feasibility.
Participant milestones
| Measure |
Mechanically Ventilated Participants
Participants were enrolled following being mechanically ventilated and had their first echocardiogram (transthoracic echocardiogram \[TTE\] and transoesophageal echocardiogram \[TOE\]) within 48 hours of mechanical ventilation. Participants were assessed every 24 hours for a further two days with daily echocardiography to monitor right and left ventricular function. Participants received standard of care including fluid, use of vasopressor drugs and renal support.
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|---|---|
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Overall Study
STARTED
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57
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Overall Study
COMPLETED
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56
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Overall Study
NOT COMPLETED
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1
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Reasons for withdrawal
| Measure |
Mechanically Ventilated Participants
Participants were enrolled following being mechanically ventilated and had their first echocardiogram (transthoracic echocardiogram \[TTE\] and transoesophageal echocardiogram \[TOE\]) within 48 hours of mechanical ventilation. Participants were assessed every 24 hours for a further two days with daily echocardiography to monitor right and left ventricular function. Participants received standard of care including fluid, use of vasopressor drugs and renal support.
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Overall Study
Protocol Violation
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1
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Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Mechanically Ventilated Participants
n=57 Participants
Participants were enrolled following being mechanically ventilated and had their first echocardiogram (TTE and TOE) within 48 hours of mechanical ventilation. Participants were assessed every 24 hours for a further two days with daily echocardiography to monitor right and left ventricular function. Participants received standard of care including fluid, use of vasopressor drugs and renal support.
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|---|---|
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Age, Continuous
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63.74 Years
STANDARD_DEVIATION 12.807 • n=57 Participants
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Sex: Female, Male
Female
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24 Participants
n=57 Participants
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Sex: Female, Male
Male
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33 Participants
n=57 Participants
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Region of Enrollment
France
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57 Participants
n=57 Participants
|
PRIMARY outcome
Timeframe: Days 1, 2 and 3Population: Evaluable Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
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.
Outcome measures
| Measure |
Mechanically Ventilated Participants
n=44 Participants
Participants were enrolled following being mechanically ventilated and had their first echocardiogram (TTE and TOE) within 48 hours of mechanical ventilation. Participants were assessed every 24 hours for a further two days with daily echocardiography to monitor right and left ventricular function. Participants received standard of care including fluid, use of vasopressor drugs and renal support.
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|---|---|
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Renin-angiotensin System Cascade Biomarker to Include Angiotensin (Ang) II Level
Day 1, n=44
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41.693 Picograms per milliliter
Standard Deviation 67.4893
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Renin-angiotensin System Cascade Biomarker to Include Angiotensin (Ang) II Level
Day 2, n=43
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43.861 Picograms per milliliter
Standard Deviation 110.6191
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Renin-angiotensin System Cascade Biomarker to Include Angiotensin (Ang) II Level
Day 3, n=35
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27.801 Picograms per milliliter
Standard Deviation 49.1054
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PRIMARY outcome
Timeframe: Days 1, 2 and 3Population: Evaluable Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Right ventricular size ratio was measured using TTE or TOE.
Outcome measures
| Measure |
Mechanically Ventilated Participants
n=45 Participants
Participants were enrolled following being mechanically ventilated and had their first echocardiogram (TTE and TOE) within 48 hours of mechanical ventilation. Participants were assessed every 24 hours for a further two days with daily echocardiography to monitor right and left ventricular function. Participants received standard of care including fluid, use of vasopressor drugs and renal support.
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|---|---|
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Ratio of RV to Left Ventricular (LV) End-diastolic Area (RV Size Ratio)
Day 1, n=45
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0.653 Ratio
Standard Deviation 0.2418
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|
Ratio of RV to Left Ventricular (LV) End-diastolic Area (RV Size Ratio)
Day 2, n=42
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0.655 Ratio
Standard Deviation 0.2276
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Ratio of RV to Left Ventricular (LV) End-diastolic Area (RV Size Ratio)
Day 3, n=35
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0.634 Ratio
Standard Deviation 0.1662
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PRIMARY outcome
Timeframe: Days 1, 2 and 3Population: Evaluable Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
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.
Outcome measures
| Measure |
Mechanically Ventilated Participants
n=43 Participants
Participants were enrolled following being mechanically ventilated and had their first echocardiogram (TTE and TOE) within 48 hours of mechanical ventilation. Participants were assessed every 24 hours for a further two days with daily echocardiography to monitor right and left ventricular function. Participants received standard of care including fluid, use of vasopressor drugs and renal support.
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|---|---|
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Number of Participants With Paradoxical Septal Motion
Day 1, n=43
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5 Participants
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Number of Participants With Paradoxical Septal Motion
Day 2, n=41
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11 Participants
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Number of Participants With Paradoxical Septal Motion
Day 3, n=34
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10 Participants
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PRIMARY outcome
Timeframe: Days 1, 2 and 3Population: Evaluable Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Pulmonary arterial systolic pressure was measured using TTE or TOE.
Outcome measures
| Measure |
Mechanically Ventilated Participants
n=39 Participants
Participants were enrolled following being mechanically ventilated and had their first echocardiogram (TTE and TOE) within 48 hours of mechanical ventilation. Participants were assessed every 24 hours for a further two days with daily echocardiography to monitor right and left ventricular function. Participants received standard of care including fluid, use of vasopressor drugs and renal support.
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|---|---|
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Pulmonary Arterial Systolic Pressure at Indicated Time Points
Day 1, n=38
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36.350 Millimeters of mercury
Standard Deviation 15.7070
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Pulmonary Arterial Systolic Pressure at Indicated Time Points
Day 2, n=39
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35.564 Millimeters of mercury
Standard Deviation 12.2985
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Pulmonary Arterial Systolic Pressure at Indicated Time Points
Day 3, n=29
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37.224 Millimeters of mercury
Standard Deviation 13.3521
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PRIMARY outcome
Timeframe: Days 1, 2 and 3Population: Evaluable Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Right atrial pressure is the blood pressure in the right atrium of the heart. Right atrial pressure was measured by TTE or TOE.
Outcome measures
| Measure |
Mechanically Ventilated Participants
n=42 Participants
Participants were enrolled following being mechanically ventilated and had their first echocardiogram (TTE and TOE) within 48 hours of mechanical ventilation. Participants were assessed every 24 hours for a further two days with daily echocardiography to monitor right and left ventricular function. Participants received standard of care including fluid, use of vasopressor drugs and renal support.
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|---|---|
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Right Atrial Pressure at Indicated Time Points
Day 1, n=42
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9.055 Millimeters of mercury
Standard Deviation 4.5279
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Right Atrial Pressure at Indicated Time Points
Day 2, n=40
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9.425 Millimeters of mercury
Standard Deviation 5.0530
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Right Atrial Pressure at Indicated Time Points
Day 3, n=34
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9.456 Millimeters of mercury
Standard Deviation 4.7456
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PRIMARY outcome
Timeframe: Days 1, 2 and 3Population: Evaluable Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
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.
Outcome measures
| Measure |
Mechanically Ventilated Participants
n=41 Participants
Participants were enrolled following being mechanically ventilated and had their first echocardiogram (TTE and TOE) within 48 hours of mechanical ventilation. Participants were assessed every 24 hours for a further two days with daily echocardiography to monitor right and left ventricular function. Participants received standard of care including fluid, use of vasopressor drugs and renal support.
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|---|---|
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Inferior Vena Cava Diameter at End Expiration at Indicated Time Points
Day 1, n=38
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18.529 Millimeter
Standard Deviation 4.8940
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Inferior Vena Cava Diameter at End Expiration at Indicated Time Points
Day 2, n=41
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18.412 Millimeter
Standard Deviation 5.5483
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Inferior Vena Cava Diameter at End Expiration at Indicated Time Points
Day 3, n=34
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17.915 Millimeter
Standard Deviation 5.0126
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PRIMARY outcome
Timeframe: Up to Day 3Population: Evaluable Population.
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).
Outcome measures
| Measure |
Mechanically Ventilated Participants
n=45 Participants
Participants were enrolled following being mechanically ventilated and had their first echocardiogram (TTE and TOE) within 48 hours of mechanical ventilation. Participants were assessed every 24 hours for a further two days with daily echocardiography to monitor right and left ventricular function. Participants received standard of care including fluid, use of vasopressor drugs and renal support.
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|---|---|
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Pearson Correlation Coefficient Between PASP and Ang II Level
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-0.019 Unitless
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PRIMARY outcome
Timeframe: Up to Day 3Population: Evaluable Population.
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.
Outcome measures
| Measure |
Mechanically Ventilated Participants
n=45 Participants
Participants were enrolled following being mechanically ventilated and had their first echocardiogram (TTE and TOE) within 48 hours of mechanical ventilation. Participants were assessed every 24 hours for a further two days with daily echocardiography to monitor right and left ventricular function. Participants received standard of care including fluid, use of vasopressor drugs and renal support.
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|---|---|
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Pearson Correlation Coefficient Between RV Size Ratio and Ang II Level
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0.153 Unitless
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SECONDARY outcome
Timeframe: Days 1, 2 and 3Population: At risk Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
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.
Outcome measures
| Measure |
Mechanically Ventilated Participants
n=56 Participants
Participants were enrolled following being mechanically ventilated and had their first echocardiogram (TTE and TOE) within 48 hours of mechanical ventilation. Participants were assessed every 24 hours for a further two days with daily echocardiography to monitor right and left ventricular function. Participants received standard of care including fluid, use of vasopressor drugs and renal support.
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Number of Participants With Pulmonary Circulatory Dysfunction
Day 1, n=56
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18 Participants
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Number of Participants With Pulmonary Circulatory Dysfunction
Day 2, n=52
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12 Participants
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Number of Participants With Pulmonary Circulatory Dysfunction
Day 3, n=43
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5 Participants
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SECONDARY outcome
Timeframe: Days 1, 2 and 3Population: At risk Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
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.
Outcome measures
| Measure |
Mechanically Ventilated Participants
n=56 Participants
Participants were enrolled following being mechanically ventilated and had their first echocardiogram (TTE and TOE) within 48 hours of mechanical ventilation. Participants were assessed every 24 hours for a further two days with daily echocardiography to monitor right and left ventricular function. Participants received standard of care including fluid, use of vasopressor drugs and renal support.
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|---|---|
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Number of Participants With Acute Cor Pulmonale
Day 1, n=56
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5 Participants
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Number of Participants With Acute Cor Pulmonale
Day 2, n=52
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10 Participants
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Number of Participants With Acute Cor Pulmonale
Day 3, n=43
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8 Participants
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SECONDARY outcome
Timeframe: Days 1, 2 and 3Population: At risk Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
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.
Outcome measures
| Measure |
Mechanically Ventilated Participants
n=56 Participants
Participants were enrolled following being mechanically ventilated and had their first echocardiogram (TTE and TOE) within 48 hours of mechanical ventilation. Participants were assessed every 24 hours for a further two days with daily echocardiography to monitor right and left ventricular function. Participants received standard of care including fluid, use of vasopressor drugs and renal support.
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|---|---|
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Number of Participants With Severe Acute Cor Pulmonale
Day 1, n=56
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3 Participants
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Number of Participants With Severe Acute Cor Pulmonale
Day 2, n=52
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0 Participants
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Number of Participants With Severe Acute Cor Pulmonale
Day 3, n=43
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0 Participants
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SECONDARY outcome
Timeframe: Days 1, 2 and 3Population: Evaluable Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Blood samples were collected for renin-angiotensin system biomarkers at indicated time points.
Outcome measures
| Measure |
Mechanically Ventilated Participants
n=44 Participants
Participants were enrolled following being mechanically ventilated and had their first echocardiogram (TTE and TOE) within 48 hours of mechanical ventilation. Participants were assessed every 24 hours for a further two days with daily echocardiography to monitor right and left ventricular function. Participants received standard of care including fluid, use of vasopressor drugs and renal support.
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|---|---|
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Renin-angiotensin System Cascade Biomarker: Ang(1-7) Level
Day 1, n=44
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6.038 Picograms per milliliter
Standard Deviation 11.7629
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Renin-angiotensin System Cascade Biomarker: Ang(1-7) Level
Day 2, n=44
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6.020 Picograms per milliliter
Standard Deviation 11.3192
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Renin-angiotensin System Cascade Biomarker: Ang(1-7) Level
Day 3, n=36
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4.911 Picograms per milliliter
Standard Deviation 7.8364
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SECONDARY outcome
Timeframe: Days 1, 2 and 3Population: Evaluable Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Blood samples were collected for renin-angiotensin system biomarkers at indicated time points.
Outcome measures
| Measure |
Mechanically Ventilated Participants
n=44 Participants
Participants were enrolled following being mechanically ventilated and had their first echocardiogram (TTE and TOE) within 48 hours of mechanical ventilation. Participants were assessed every 24 hours for a further two days with daily echocardiography to monitor right and left ventricular function. Participants received standard of care including fluid, use of vasopressor drugs and renal support.
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|---|---|
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Renin-angiotensin System Cascade Biomarker: Ang II/ Ang(1-7) Ratio
Day 1, n=44
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10.620 Ratio
Standard Deviation 10.1424
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Renin-angiotensin System Cascade Biomarker: Ang II/ Ang(1-7) Ratio
Day 2, n=43
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9.184 Ratio
Standard Deviation 7.3338
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Renin-angiotensin System Cascade Biomarker: Ang II/ Ang(1-7) Ratio
Day 3, n=35
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7.938 Ratio
Standard Deviation 8.0332
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SECONDARY outcome
Timeframe: Up to Day 3Population: Evaluable Population.
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.
Outcome measures
| Measure |
Mechanically Ventilated Participants
n=45 Participants
Participants were enrolled following being mechanically ventilated and had their first echocardiogram (TTE and TOE) within 48 hours of mechanical ventilation. Participants were assessed every 24 hours for a further two days with daily echocardiography to monitor right and left ventricular function. Participants received standard of care including fluid, use of vasopressor drugs and renal support.
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|---|---|
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Pearson Correlation Coefficient Between PASP and Ang(1-7)
|
-0.050 Unitless
|
SECONDARY outcome
Timeframe: Up to Day 3Population: Evaluable Population.
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.
Outcome measures
| Measure |
Mechanically Ventilated Participants
n=45 Participants
Participants were enrolled following being mechanically ventilated and had their first echocardiogram (TTE and TOE) within 48 hours of mechanical ventilation. Participants were assessed every 24 hours for a further two days with daily echocardiography to monitor right and left ventricular function. Participants received standard of care including fluid, use of vasopressor drugs and renal support.
|
|---|---|
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Pearson Correlation Coefficient Between PASP and Ang II/Ang(1-7)
|
0.193 Unitless
|
SECONDARY outcome
Timeframe: Up to Day 3Population: Evaluable Population.
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.
Outcome measures
| Measure |
Mechanically Ventilated Participants
n=45 Participants
Participants were enrolled following being mechanically ventilated and had their first echocardiogram (TTE and TOE) within 48 hours of mechanical ventilation. Participants were assessed every 24 hours for a further two days with daily echocardiography to monitor right and left ventricular function. Participants received standard of care including fluid, use of vasopressor drugs and renal support.
|
|---|---|
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Pearson Correlation Coefficient Between RV Size Ratio and Ang(1-7)
|
0.350 Unitless
|
SECONDARY outcome
Timeframe: Up to Day 3Population: Evaluable Population.
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.
Outcome measures
| Measure |
Mechanically Ventilated Participants
n=45 Participants
Participants were enrolled following being mechanically ventilated and had their first echocardiogram (TTE and TOE) within 48 hours of mechanical ventilation. Participants were assessed every 24 hours for a further two days with daily echocardiography to monitor right and left ventricular function. Participants received standard of care including fluid, use of vasopressor drugs and renal support.
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|---|---|
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Pearson Correlation Coefficient Between RV Size Ratio and Ang II/Ang(1-7)
|
-0.032 Unitless
|
Adverse Events
Mechanically Ventilated Participants
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER