Clinical trial NCT03212690: Study of Renin-angiotensin System in Mechanically Ventilated Subjects
Official title: Study to Elucidate the Association of the Renin-angiotensin System and Right Ventricular Function in Mechanically Ventilated Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Acute Lung Injury
Keywords: mechanical ventilation
echocardiography
right ventricular function
Ang (1-7)
Ang II
Renin-angiotensin system
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2017-07-11
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Renin-angiotensin System Cascade Biomarker to Include Angiotensin (Ang) II Level
timeFrame: Days 1, 2 and 3
measure: Ratio of RV to Left Ventricular (LV) End-diastolic Area (RV Size Ratio)
timeFrame: Days 1, 2 and 3
measure: Number of Participants With Paradoxical Septal Motion
timeFrame: Days 1, 2 and 3
measure: Pulmonary Arterial Systolic Pressure at Indicated Time Points
timeFrame: Days 1, 2 and 3
measure: Right Atrial Pressure at Indicated Time Points
timeFrame: Days 1, 2 and 3
measure: Inferior Vena Cava Diameter at End Expiration at Indicated Time Points
timeFrame: Days 1, 2 and 3
measure: Pearson Correlation Coefficient Between PASP and Ang II Level
timeFrame: Up to Day 3
measure: Pearson Correlation Coefficient Between RV Size Ratio and Ang II Level
timeFrame: Up to Day 3
Secondary outcomes:
measure: Number of Participants With Pulmonary Circulatory Dysfunction
timeFrame: Days 1, 2 and 3
measure: Number of Participants With Acute Cor Pulmonale
timeFrame: Days 1, 2 and 3
measure: Number of Participants With Severe Acute Cor Pulmonale
timeFrame: Days 1, 2 and 3
measure: Renin-angiotensin System Cascade Biomarker: Ang(1-7) Level
timeFrame: Days 1, 2 and 3
measure: Renin-angiotensin System Cascade Biomarker: Ang II/ Ang(1-7) Ratio
timeFrame: Days 1, 2 and 3
measure: Pearson Correlation Coefficient Between PASP and Ang(1-7)
timeFrame: Up to Day 3
measure: Pearson Correlation Coefficient Between PASP and Ang II/Ang(1-7)
timeFrame: Up to Day 3
measure: Pearson Correlation Coefficient Between RV Size Ratio and Ang(1-7)
timeFrame: Up to Day 3
measure: Pearson Correlation Coefficient Between RV Size Ratio and Ang II/Ang(1-7)
timeFrame: Up to Day 3
Other outcomes:
Locations:
city: Boulogne-Billancourt
country: France
facility: GSK Investigational Site
city: Créteil
country: France
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: