Reduction of myocardial and kidney injury risk of post cardiac surgery by increasing the expression of genes that promote myocardial mitochondrial homeostasis via effects on chromatin histone deacetylation. MedDRA version: 21.1 Level: PT Classification code 10069339 Term: Acute kidney injury System Organ Class: 10038359 - Renal and urinary disorders MedDRA version: 20.1 Level: LLT
Conditions
Interventions
Trade Name: Epilim Chrono
Product Name: Epilim Chrono
Pharmaceutical Form: Gastro-resistant tablet
INN or Proposed INN: Sodium Valproate
Sponsors
University of Leicester
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participant may enter the trial if ALL of the following apply 1. Adult cardiac surgery patients (=18 years) undergoing cardiac surgery (CABG, Valve, or CABG and Valve) with cardiopulmonary bypass. 2. Able, in the opinion of the investigator, and willing to give informed consent. 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 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 82
Exclusion criteria
Exclusion criteria: Participant may not enter trial if ANY of the following apply: 1. Emergency or salvage procedure 2. Patients with end stage renal failure defined as an estimated Glomerular Filtration rate (eGFR) <15 mL/min/1.72 m2 calculated from the Modification of Diet in Renal Disease equation,1 or patients who are on long-term haemodialysis or have undergone renal transplantation. 3. Patients with persistent or chronic atrial fibrillation. 4. Patients with acute liver disease. 5. Patients with a family history of severe liver disease. 6. Patients allergic to sodium valproate. 7. Patients with thrombocytopaenia (platelet count <150x109 per mL). 8. Patients taking long-term Histone Deacetylase Inhibitors such as sodium valproate. 9. Patients taking anti-epileptic medication. 10. Patients diagnosed with a mitochondrial deficiency disorder. 11. Patients with porphyria. 12. Patients with known urea cycle disorders. 13. Women of child bearing potential (WOCBP) are excluded from the study. A woman is defined as being of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal, unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. 14. Patients who are participating in another interventional clinical trial. 15. Unable, in the opinion of the investigator, or unwilling to give informed consent protocol. Exclusion criteria for optional MRI study 1. Permanent pacemaker or ICD 2. Brain Aneurysm Clip 3. Implanted neural stimulator 4. Cochlear implant (specific implant must be checked that it is MRI safe) 5. Ocular foreign body (e.g. metal shavings) unless removed 6. Other implanted medical devices: (e.g. Swan Ganz catheter) 7. Insulin pump 8. Retained metal shrapnel or bullet
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The co-primary endpoint will be measured using serial biomarkers of renal and myocardial injury in all patients in the trial. ; Main Objective: The Val-CARD trial tries to answer the question “Does the drug sodium valproate reduce complications affecting the heart and kidneys in patients having heart operations?” through a two phase design, in which the first phase aims to find the optimum dosing regimen that is best tolerated by patients. ;Secondary Objective: The secondary research questions are: "Does the drug sodium valproate reduce: the failure of multiple organs (like the lungs, kidney or abdominal organs); length of hospital stay; bleeding; infection or death?"; Timepoint(s) of evaluation of this end point: 1. Kidney: Serum creatinine measured at baseline, on return to ITU, and at 6-12, 24, 48, 72, 96 hours, 6 weeks and 3 months postoperatively. 2. Myocardium: Serum troponin measured at baseline, on return to ITU, and at 6-12, 24, 48 and 72 hours postoperatively | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Adverse events, other than those included in the primary and secondary endpoints. - Post-surgery organ injury assessed by SOFA scores at baseline, pre-assessment, surgery and 24, 48, 72 and 96 hours post-surgery. - Sepsis-related Organ Failure Assessment Score pre-surgery, and at 24, 48, 72 and 96 hours post-surgery. - Urinary AKI biomarkers pre-surgery, and at 6-12 and 24 post-surgery. - Absolute change from baseline for serum creatinine. - Serum creatinine and eGFR at 6 weeks post-surgery using the Modification of Diet in Renal Disease equation. - Lung Injury; Arterial alveolar oxygen ratios immediately pre-surgery, and at 24, 48, 72 and 96 hours post-surgery. - GI Tract Injury: Serum amylase and liver function tests immediately pre-surgery, and at 24, 48, 72 and 96 hours post-surgery. - Hospital stay and cumulative resource use: time until extubation, discharge from HDU and discharge from hospital will all be measured from the start of surgery; deaths will be censored at time of death - The following clinical adverse events will be recorded: - Sepsis will be defined as suspected or documented infection and an acute change in total SOFA score =2 points consequent to the infection.2 For the purposes of the study suspected or documented infection will be defined as the commencement of intravenous antibiotics. The rise in SOFA score will be assessed within 72 hours of the commencement of antibiotics. - Peak lactate within 24 hours of surgery and time to resolution of hyperlactataemia (arterial serum lactate >2.5 mmol/L) post peak. - Acute Kidney Injury defined as KDIGO stage 1, 2 or 3.3 - Acute lung injury, defined as per the Berlin ARDS guidance.4 - Low cardiac output, defined as new intra-or postoperative intra-aortic b | — |
Countries
United Kingdom
Outcome results
None listed