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Study of Renin-angiotensin System in Mechanically Ventilated Subjects

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ClinicalTrials.gov Identifier: NCT03212690
Recruitment Status : Recruiting
First Posted : July 11, 2017
Last Update Posted : August 3, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

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.

Condition or disease Intervention/treatment
Acute Lung Injury Drug: Local standard of care Procedure: Mechanical ventilation

Study Type : Observational
Estimated Enrollment : 150 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Study to Elucidate the Association of the Renin-angiotensin System and Right Ventricular Function in Mechanically Ventilated Patients
Actual Study Start Date : June 11, 2018
Estimated Primary Completion Date : September 16, 2019
Estimated Study Completion Date : September 16, 2019


Group/Cohort Intervention/treatment
Mechanically ventilated subjects
Subjects who are receiving invasive mechanical ventilation (Duration of ventilation <=24 hours) will be evaluated using standard care investigations.
Drug: Local standard of care
Local standard of care will include fluid resuscitation, use of vasopressor drugs and renal support.

Procedure: Mechanical ventilation
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).




Primary Outcome Measures :
  1. Assessment of Ang II levels [ Time Frame: Up to Day 3 ]
    To evaluate the association between plasma Ang II levels and RV function plasma samples (collected at the same time of echocardiography).

  2. Ratio of right ventricular to left ventricular end-diastolic area to evaluate association between plasma Ang II levels and RV function [ Time Frame: Up to Day 3 ]
    Evaluation of ratio of right ventricular to left ventricular end-diastolic area recorded from TTE and/or TOE.

  3. Assessment of Paradoxical septal motion to evaluate association between plasma Ang II levels and RV function [ Time Frame: Up to Day 3 ]
    To evaluate septal motion. TTE and/or TOE will be used for the evaluation.

  4. Assessment of pulmonary arterial systolic pressure (PASP) to evaluate association between plasma Ang II levels and RV function [ Time Frame: Up to Day 3 ]
    TTE and/or TOE will be used for the evaluation. PASP will be estimated from trans-tricuspid pressure and right atrial pressure or inferior vena cava (IVC) diameter.


Secondary Outcome Measures :
  1. Number of subjects with presence of Pulmonary Circulatory Dysfunction (PCD) and severe PCD [ Time Frame: Up to Day 3 ]
    PCD is defined as moderate dysfunction (PASP [40 millimeter of mercury (mmHg) or a dilated RV end diastolic RV/left ventricle (LV) area ratio 0.6] but without septal dyskinesia).

  2. Number of subjects with presence of Acute Cor Pulmonale (ACP) and severe ACP [ Time Frame: Up to Day 3 ]
    ACP 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. Severe ACP is defined as severely dilated RV (end-diastolic RV/LV area ratio greater than or equal to 1) with septal dyskinesia.

  3. Assessment of Ang (1-7) levels [ Time Frame: Up to Day 3 ]
    Blood samples will be collected at the same time of echocardiography for the evaluation of Ang (1-7) levels.

  4. Ratio of Ang II/ Ang (1-7) [ Time Frame: Up to Day 3 ]
    Blood samples will be collected at the same time of echocardiography for evaluation.

  5. Ratio of right ventricular to left ventricular end-diastolic area to evaluate association between plasma Ang(1-7) levels, Ang II/Ang(1-7) ratio and RV function. [ Time Frame: Up to Day 3 ]
    Ratio of right ventricular to left ventricular end-diastolic area will be recorded from TTE and/or TOE.

  6. Assessment of Paradoxical septal motion to evaluate association between plasma Ang (1-7) levels, Ang II/Ang (1-7) ratio and RV function. [ Time Frame: Up to Day 3 ]
    TTE and/or TOE will be used for the evaluation.

  7. Assessment of PASP to evaluate between plasma Ang (1-7) levels, Ang II/Ang (1-7) ratio and RV function. [ Time Frame: Up to Day 3 ]
    TTE and/or TOE will be used for the evaluation. PASP will be estimated from trans-tricuspid pressure and right atrial pressure or IVC diameter.



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Subjects receiving invasive mechanical ventilation with duration of ventilation of less than equal to 24 hours.
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 24 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 24-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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03212690


Contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

Locations
France
GSK Investigational Site Recruiting
Boulogne-Billancourt, France, 92100
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
Créteil, France, 94000
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03212690     History of Changes
Other Study ID Numbers: 205821
First Posted: July 11, 2017    Key Record Dates
Last Update Posted: August 3, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (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
URL: http://clinicalstudydatarequest.com

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GlaxoSmithKline:
mechanical ventilation
echocardiography
right ventricular function
Ang (1-7)
Ang II
Renin-angiotensin system

Additional relevant MeSH terms:
Lung Injury
Acute Lung Injury
Respiratory Distress Syndrome, Adult
Lung Diseases
Respiratory Tract Diseases
Thoracic Injuries
Wounds and Injuries
Respiration Disorders