Acute Respiratory Distress Syndrome, post-operative coronary artery bypass graft patients Respiratory
Conditions
Interventions
Patients will be randomised 1:1 to either a standard care arm or treatment (metformin arm) using the sealed envelope platform.
In the treatment arm of the trial, patients will receive a total of 14 da
Sponsors
Belfast Health and Social Care Trust
Eligibility
Sex/Gender
All
Age
18 Years to 110 Years
Inclusion criteria
Inclusion criteria: Adult patients =18 years of age undergoing elective coronary artery bypass graft surgery using cardiopulmonary bypass.
Exclusion criteria
Exclusion criteria: 1. Age 3x upper limit of normal 8. Patients with known mitochondrial disorders 9. Inability to take oral medication pre-operatively 10. Known hypersensitivity or intolerance to the study medication 11. Lack of capacity to consent to trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Plasma RAGE measured using ELISA from baseline to immediately post cardiopulmonary bypass (RAGEimmediately post bypass – RAGEimmediately pre bypass) | — |
Secondary
| Measure | Time frame |
|---|---|
| At baseline and post-operative timepoints unless noted: 1. Inflammation 1.1. Total and differential white blood cell count and plasma NETs (neutrophil extracellular traps) measured using automated hematology analyser 1.2. Plasma markers of inflammation - CRP, TNFa, sTNFR, IL-6, IL-8, IL-18, IL-1Ra measured using immunoassay 2. Markers of organ or cell injury 2.1. Type I alveolar epithelial cell dysfunction – In addition to the timepoints for the primary outcome, plasma RAGE will be taken using ELISA at 24, 48 and 72 hours. 2.2. Type II alveolar epithelial cell dysfunction – measured by plasma SP-D measured using ELISA 2.3. Endothelial dysfunction – plasma vWF, Ang2 measured using ELISA 2.4. Urinary markers of injury – NGAL, Albumin: Creatinine ratio measured using ELISA Additional outcomes: 3. Mechanistic effects of metformin 3.1. Anti-inflammatory: a. PBMC AMPK phosphorylation from PBMCs +/- LPS ex vivo stimulation b. PBMC NFkB in PBMCs +/- LPS ex vivo stimulation c. PBMC inflammasome activation in PBMC +/- LPS ex vivo stimulation; including ASC speck formation, flow cytometry, IL-1beta/IL-18/LDH, caspase 1, gasdermin and other inflammasome markers. d. GDF 15 3.2. Mitochondrial modulation a. Blood mtDNA b. PBMC Mitophagy markers (PNIK1, PARKIN, MFN2, NIX, LC3-II, LAMP2) on lysates from PBMC +/- ex vivo LPS stimulation 3.3. Blood transcriptome 3.4. Blood epigenome 3.5. Muscle transcriptome and muscle/plasma metabolome 4. Clinical outcomes: 4.1. Clinical outcomes will be recorded although it is recognised the study will not be powered for these. Outcomes include rate of post-operative pneumonia, rate of acute kidney injury; post-operative neurological dysfunction; rate of wound infection; prolonged ventilation (>24 hours after procedure); rate of re-operation on the same hospital admission; length of hospital stay; length of hospital stay; inpatient and 30 day mortality. 5. Muscle mass and strength: 5.1. Mid-thigh circumference and grip strength manometry will | — |
Countries
United Kingdom
Contacts
Public ContactJonathan Strickland
Outcome results
None listed