Brain injury during open heart valve surgery MedDRA version: 21.1 Level: PT Classification code 10067967 Term: Brain injury System Organ Class: 10029205 - Nervous system disorders MedDRA version: 21.1 Level: LLT Classification code 10048935 Term: Open heart surgery System Organ Class: 100000004865 MedDRA version: 20.0 Level: LLT Classification code 10077808 Term: Mild neurocognitive disorder System Organ Class: 10029205 - Nervous system disorders MedDRA version: 20.0 Level: PT Classification
Conditions
Interventions
Trade Name: Medical carbon dioxide
Product Name: Medical carbon dioxide
Product Code: PL 0735/5006R
Pharmaceutical Form: Medicinal gas, compressed
INN or Proposed INN: Carbon dioxide
Concentration uni
Sponsors
University Hospitals Bristol and Weston NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 50 years 2. Planned left side aortic or mitral valve surgical repair or replacement (with or without another procedure, e.g. coronary artery bypass graft) via a partial or full sternotomy using central aortic perfusion cannulae Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 300 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 404
Exclusion criteria
Exclusion criteria: 1. Contraindication to medical carbon dioxide: acquired or genetic of acidosis (i.e. renal tubular acidosis) 2. Contraindication to MRI (e.g. known intolerance, permanent pacemaker in situ or expected implantation of a permanent pacemaker) 3. History of clinical stroke within 3 months prior to randomisation 4. Cardiac catheterisation within 3 days of the planned surgery 5. Cerebral and/or aortic arch arteriography or interventions within 3 days of the planned surgery 6. Active endocarditis at time of randomisation 7. Planned concomitant aortic procedure such as root replacement 8. Clinical signs of cardiogenic shock or treatment with IV inotropic therapy prior to randomisation 9. Participation in an interventional (drug or device) trial 10. Unable to provide written informed consent 11. Prisoners
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main aim is to evaluate the effectiveness and safety of carbon dioxide insufflation during open heart surgery compared to medical air in patients who are having open heart valve surgery. The primary objective is the difference in incidence of acute clinical or radiographic ischemic brain injury, between 2 and 10 days post procedure, between the group that have carbon dioxide insufflation during surgery and the group that have medical air insufflation during surgery.;Secondary Objective: Secondary objectives are: 1. The difference between the carbon dioxide group and medical air group with respect to; clinical outcomes; brain MRI outcomes; adverse events; and patient-reported outcomes. 2. The association between the burden and location of new lesions demonstrating brain injury detected on the brain MRI and post-operative neurocognitive dysfunction assessed by standard neurocognitive function tests.;Primary end point(s): The primary outcome is acute ischemic brain injury within 10 days post-surgery based on new brain lesions identified with diffusion weight magnetic resonance imaging of the brain or clinical evidence of permanent brain injury according to the updated definition of stroke for the 21st century: symptoms persisting = 24 hours in the brain, spinal cord or/and retina; not including cases of global ischemia. ;Timepoint(s) of evaluation of this end point: The primary outcome will be the time from start of surgery to hospital discharge. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Number and volume of DWI brain lesions 2. Objective quantification of the impairment caused by new ischemic brain injury assessed using the National Institutes of Health Stroke Scale (NIHSS) 3. Delirium assessed using the 3-minute diagnostic interview for Confusion Assessment Method (CAM) 4. Functional status assessed using the Barthel Index score 5. Neurocognitive function in 6 domains (verbal memory, visual memory, executive functioning, visuospatial or constructional praxis, attention, and information processing speed), assessed using the following tests: a. Addenbrooke’s Cognitive Examination III b. Trail making Tests A and B 6. Quality of life assessed using the physical and mental subscales of the 12-Item Short-Form Health Survey (SF-12) 7. Composite of all-cause mortality, clinical stroke, or acute kidney injury within 30 days of surgery 8. Serious adverse events (SAEs) to 3 months 9. Survival to 3 months ;Timepoint(s) of evaluation of this end point: Secondary outcomes will be measured at baseline (before surgery), following surgery during the inpatient stay and at the three month follow up visit. | — |
Countries
United Kingdom
Contacts
Public ContactRachel Todd
Bristol Trials Centre, Clinical Trials and Evaluations Unit, University of Bristol
Outcome results
None listed