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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-A01653-50 | Registry Identifier | Biological Research and Collections |
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Study stopped early following termination of associated clinical development program (due to lack of efficacy)
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Mechanically ventilated subjects | Experimental | Subjects receiving invasive mechanical ventilation (Duration of ventilation <=48 hours) will be evaluated using standard care investigations. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Local standard of care | Drug | Local standard of care will include fluid resuscitation, use of vasopressor drugs and renal support. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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. | Days 1, 2 and 3 |
| Pulmonary Arterial Systolic Pressure at Indicated Time Points | Pulmonary arterial systolic pressure was measured using TTE or TOE. | 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. | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Boulogne-Billancourt | 92100 | France | |||
| GSK Investigational Site |
IPD for this study will be made available via the Clinical Study Data Request site.
IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted when justified, for up to another 12 months
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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Mechanically Ventilated 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Evaluable Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). | Posted | Mean | Standard Deviation | Picograms per milliliter | Days 1, 2 and 3 |
|
Adverse events and serious adverse events were collected up to Day 3
Safety Population consisted of all participants for whom at least one echocardiograph and/or blood sample has been taken, and who did not retrospectively withdraw the consent.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Mechanically Ventilated 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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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 | GSKClinicalSupportHD@gsk.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 30, 2019 | Mar 12, 2020 | SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Feb 27, 2019 | Mar 19, 2020 | Prot_001.pdf |
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| ID | Term |
|---|---|
| D055371 | Acute Lung Injury |
| ID | Term |
|---|---|
| D055370 | Lung Injury |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D012121 | Respiration, Artificial |
| ID | Term |
|---|---|
| D058109 | Airway Management |
| D013812 | Therapeutics |
| D012151 | Resuscitation |
| D004638 | Emergency Treatment |
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| Mechanical ventilation | Procedure | 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). |
|
| 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). | 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. | Up to Day 3 |
| 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. | 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. | 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. | 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. | Days 1, 2 and 3 |
| 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. | 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. | 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. | 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. | Up to Day 3 |
| Créteil |
| 94000 |
| France |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
|
|
| Primary | Ratio of RV to Left Ventricular (LV) End-diastolic Area (RV Size Ratio) | Right ventricular size ratio was measured using TTE or TOE. | Evaluable Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). | Posted | Mean | Standard Deviation | Ratio | Days 1, 2 and 3 |
|
|
|
| Primary | 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. | Evaluable Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). | Posted | Count of Participants | Participants | Days 1, 2 and 3 |
|
|
|
| Primary | Pulmonary Arterial Systolic Pressure at Indicated Time Points | Pulmonary arterial systolic pressure was measured using TTE or TOE. | Evaluable Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). | Posted | Mean | Standard Deviation | Millimeters of mercury | Days 1, 2 and 3 |
|
|
|
| Primary | 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. | Evaluable Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). | Posted | Mean | Standard Deviation | Millimeters of mercury | Days 1, 2 and 3 |
|
|
|
| Primary | 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. | Evaluable Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). | Posted | Mean | Standard Deviation | Millimeter | Days 1, 2 and 3 |
|
|
|
| Primary | 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). | Evaluable Population. | Posted | Number | Unitless | Up to Day 3 |
|
|
|
| Primary | 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. | Evaluable Population. | Posted | Number | Unitless | Up to Day 3 |
|
|
|
| Secondary | 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. | At risk Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). | Posted | Count of Participants | Participants | Days 1, 2 and 3 |
|
|
|
| Secondary | 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. | At risk Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). | Posted | Count of Participants | Participants | Days 1, 2 and 3 |
|
|
|
| Secondary | 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. | At risk Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). | Posted | Count of Participants | Participants | Days 1, 2 and 3 |
|
|
|
| Secondary | Renin-angiotensin System Cascade Biomarker: Ang(1-7) Level | Blood samples were collected for renin-angiotensin system biomarkers at indicated time points. | Evaluable Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). | Posted | Mean | Standard Deviation | Picograms per milliliter | Days 1, 2 and 3 |
|
|
|
| Secondary | Renin-angiotensin System Cascade Biomarker: Ang II/ Ang(1-7) Ratio | Blood samples were collected for renin-angiotensin system biomarkers at indicated time points. | Evaluable Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). | Posted | Mean | Standard Deviation | Ratio | Days 1, 2 and 3 |
|
|
|
| Secondary | 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. | Evaluable Population. | Posted | Number | Unitless | Up to Day 3 |
|
|
|
| Secondary | 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. | Evaluable Population. | Posted | Number | Unitless | Up to Day 3 |
|
|
|
| Secondary | 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. | Evaluable Population. | Posted | Number | Unitless | Up to Day 3 |
|
|
|
| Secondary | 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. | Evaluable Population. | Posted | Number | Unitless | Up to Day 3 |
|
|
|
| 0 |
| 57 |
| 0 |
| 57 |
| 0 |
| 57 |
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.
| D012138 |
| Respiratory Therapy |
|
| Day 3, n=35 |
|
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| Day 3, n=34 |
|
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| Day 3, n=29 |
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| Day 3, n=34 |
|
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| Day 3, n=34 |
|
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| Day 3, n=43 |
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| Day 3, n=43 |
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| Day 3, n=43 |
|
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| Day 3, n=36 |
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| Day 3, n=35 |
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