Study of Renin-angiotensin System in Mechanically Ventilated Subjects

NCT03212690 | Terminated Results

• 2 other identifiers: 2058212017-A01653-50
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 2

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.

Conditions

Acute Lung Injury

Keywords

mechanical ventilation; echocardiography; right ventricular function; Ang (1-7); Ang II; Renin-angiotensin system

Outcome Measures

Primary Outcomes (8)

• 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.

  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

Secondary Outcomes (9)

• Number of Participants With Pulmonary Circulatory Dysfunction

  Days 1, 2 and 3

• Number of Participants With Acute Cor Pulmonale

  Days 1, 2 and 3

• Number of Participants With Severe Acute Cor Pulmonale

  Days 1, 2 and 3

• Renin-angiotensin System Cascade Biomarker: Ang(1-7) Level

  Days 1, 2 and 3

• Renin-angiotensin System Cascade Biomarker: Ang II/ Ang(1-7) Ratio

  Days 1, 2 and 3

Study Arms (1)

Mechanically ventilated subjects

EXPERIMENTAL

Subjects receiving invasive mechanical ventilation (Duration of ventilation \<=48 hours) will be evaluated using standard care investigations.

Drug: Local standard of care; Procedure: Mechanical ventilation

Interventions

Local standard of care DRUG

Local standard of care will include fluid resuscitation, use of vasopressor drugs and renal support.

Mechanically ventilated subjects

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).

Mechanically ventilated subjects

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Boulogne-Billancourt, 92100, France

Location

GSK Investigational Site

Créteil, 94000, France

Location

MeSH Terms

Conditions

Acute Lung Injury

Interventions

Respiration, Artificial

Condition Hierarchy (Ancestors)

Lung Injury; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Airway Management; Therapeutics; Resuscitation; Emergency Treatment; Respiratory Therapy

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2017
• First Posted: July 11, 2017
• Study Start: June 11, 2018
• Primary Completion: July 8, 2019
• Study Completion: July 8, 2019
• Last Updated: April 1, 2020
• Results First Posted: April 1, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
• 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

Locations

FR (2)