- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03212690
Study of Renin-angiotensin System in Mechanically Ventilated Subjects
March 19, 2020 updated by: GlaxoSmithKline
Study to Elucidate the Association of the Renin-angiotensin System and Right Ventricular Function in Mechanically Ventilated Patients
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 Overview
Status
Terminated
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
57
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Boulogne-Billancourt, France, 92100
- GSK Investigational Site
-
Créteil, France, 94000
- GSK Investigational Site
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
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:
- Male or female subject must be 18 to 80 years of age inclusive, at the time of enrolment.
- Subjects who are receiving invasive mechanical ventilation (duration of ventilation less than equal to 48 hours).
- Body mass index within the range 18.0 - 38.0 kilograms per meter square (kg/m^2, inclusive). Clinical estimate of height and weight is acceptable.
- Given subjects will be mechanically ventilated upon enrolment, obtaining informed consent directly from the subjects will not be feasible. Consent will be obtained by subject's Legally Acceptable Representative (LAR) or subject will be enrolled upon emergency consent process or subject will be enrolled by signing the informed consent.
Exclusion Criteria:
- Subjects who are moribund or whose clinical condition is deteriorating rapidly or any subject for whom the investigator does not consider there is a reasonable expectation that they will be able to complete the 3 days of observation in the study.
- Subjects undergoing elective surgery. Investigator will make every effort to ensure that the following exclusion criteria are met; however, in some instances it may not be possible to assess all of these criteria within the 48-hour window. In this case, a subject can be included and investigator will obtain the information when available.
- Chronic obstructive pulmonary disease (COPD) requiring long term oxygen treatment or home mechanical ventilation.
- Documented pre-existing chronic pulmonary hypertension.
- Massive pulmonary embolism (defined by pulmonary embolism with systemic hypotension [defined as a systolic arterial pressure less than 90 mmHg or a drop in systolic arterial pressure of at least 40 mmHg for at least 15 minutes (mins)] which is not caused by new onset arrhythmias) or shock (manifested by evidence of tissue hypo-perfusion and hypoxia, including an altered level of consciousness, oliguria, or cool, clammy extremities).
- Pulmonary vasculitis or pulmonary hemorrhage including diffuse alveolar hemorrhage.
- Lung transplantation within last 6 months.
- Cardiopulmonary arrest during concurrent illness.
- Any use of RAS modulators including Angiotensin Converting Enzyme (ACE) type 1 inhibitors, Renin inhibitors and Angiotensin Receptor Blockers within 4 days or 5.5 half live whichever is longer.
- Do not resuscitate status.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: DIAGNOSTIC
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Mechanically ventilated subjects
Subjects receiving invasive mechanical ventilation (Duration of ventilation <=48 hours) will be evaluated using standard care investigations.
|
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).
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Renin-angiotensin System Cascade Biomarker to Include Angiotensin (Ang) II Level
Time Frame: Days 1, 2 and 3
|
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)
Time Frame: Days 1, 2 and 3
|
Right ventricular size ratio was measured using TTE or TOE.
|
Days 1, 2 and 3
|
Number of Participants With Paradoxical Septal Motion
Time Frame: Days 1, 2 and 3
|
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
Time Frame: Days 1, 2 and 3
|
Pulmonary arterial systolic pressure was measured using TTE or TOE.
|
Days 1, 2 and 3
|
Right Atrial Pressure at Indicated Time Points
Time Frame: Days 1, 2 and 3
|
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
Time Frame: Days 1, 2 and 3
|
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.
|
Days 1, 2 and 3
|
Pearson Correlation Coefficient Between PASP and Ang II Level
Time Frame: Up to Day 3
|
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
Time Frame: Up to Day 3
|
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
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Pulmonary Circulatory Dysfunction
Time Frame: Days 1, 2 and 3
|
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.
|
Days 1, 2 and 3
|
Number of Participants With Acute Cor Pulmonale
Time Frame: Days 1, 2 and 3
|
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
Time Frame: Days 1, 2 and 3
|
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
Time Frame: Days 1, 2 and 3
|
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
Time Frame: Days 1, 2 and 3
|
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)
Time Frame: Up to Day 3
|
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)
Time Frame: Up to Day 3
|
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)
Time Frame: Up to Day 3
|
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)
Time Frame: Up to Day 3
|
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
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
June 11, 2018
Primary Completion (ACTUAL)
July 8, 2019
Study Completion (ACTUAL)
July 8, 2019
Study Registration Dates
First Submitted
July 6, 2017
First Submitted That Met QC Criteria
July 6, 2017
First Posted (ACTUAL)
July 11, 2017
Study Record Updates
Last Update Posted (ACTUAL)
April 1, 2020
Last Update Submitted That Met QC Criteria
March 19, 2020
Last Verified
March 1, 2020
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 205821
- 2017-A01653-50 (REGISTRY: Biological Research and Collections)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
IPD for this study will be made available via the Clinical Study Data Request site.
IPD Sharing Time Frame
IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
IPD Sharing Access Criteria
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
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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