Title: The Renoprotective value of Leukodepletion in Heart Valve surgery: an external feasibility randomised controlled trial (ROLO Trial)
Funder: Department of Health (England)

Abstract: BACKGROUND The incidence of cardiac surgery-associated acute kidney injury (CSA-AKI) is around 23%7-8 and over 50% in patients over 70yrs9, placing the older population of heart valve surgery patients (73yrs10) at significant risk. CSA-AKI is associated with higher mortality, morbidity and costs of care1,11. Acute systemic inflammation associated with exposure to the cardiopulmonary-bypass circuit may be a key contributory factor in the development of CSA-AKI12. We have demonstrated biochemical evidence for the renoprotective benefits of using a leukodepletion (LG6) filter to protect against CSA-AKI in low risk patients6, but clinical benefit was unclear. We therefore propose a feasibility trial to a) estimate parameters for a larger trial and b) to confirm or refute potential benefit by replicating the previous study in higher risk patients. AIMS To test the hypothesis: Leukodepletion during cardiopulmonary bypass reduces severity of post-operative CSA-AKI and improves clinical outcomes in patients undergoing heart valve surgery. PLAN OF INVESTIGATION This will be a single centre, double blind, randomised, controlled parallel group external feasibility trial conducted in a regional cardiothoracic centre. P atients scheduled for elective heart valve surgery will be screened for eligibility, excluding those with insufficient baseline renal function to benefit from the intervention or where contraindicated. We will stratify randomisation by pre-operative risk of CSA-AKI. Both the surgeon and research nurse will be blinded to the nature of the filter. Consenting patients will be randomised to receive surgery as follows: I ntervention, an arterial line leukodepletion filter (LG6) on the CPB circuit, or the C omparator, a standard arterial line filter. O utcomes will be measured in the acute phase over the first 5 post-operative days, and at 6- and 12-week follow-up. The primary outcome is acute kidney injury as defined by the KDIGO criteria which are endorsed by the Renal Association13. Secondary outcomes include: tubular kidney injury (RBP:Cr and KIM-1:Cr), glomerular kidney injury (A:Cr and Cystatin C), diuretic dosage, daily fluid balance, adverse events (mortality, CVVH, infection rates), length of post-operative stay (ICU and hospital), health economics and health-related quality of life. To estimate the proportion of patients experiencing any KDIGO-defined CSA-AKI stage we propose to recruit and follow-up 108 patients over a period of 17 months during the 24-month study timeline. Since this will be an external feasibility trial, we will estimate the effect size (relative risk and 95% CI), although clearly the trial will not be powered to detect an important clinical difference in the proportions of patients experiencing AKI. While the estimated treatment effect will be a consideration, the target relative risk for a subsequent larger trial will be based primarily on consensus about what would constitute a clinically important reduction in the proportion of patients experiencing AKI. Levels of biomarkers over time will be compared using mixed regression models, including main effects for group, time and group-by-time interaction. The economic evaluation will be expressed as an incremental cost per QALY. Other outcomes will be summarised descriptively. BENEFITS TO PATIENTS AND NHS Acute kidney injury is life threatening and a frequent serious complication after cardiac surgery. Reducing its incidence would benefit both the cardiac surgery population and the NHS Trusts through a reduction in post-operative intensive care and hospital stay. This feasibility trial is a key step in the translational evaluation of this inexpensive filter, providing vital information required for the next stage of translation, i.e. the design of a large, pragmatic multicentre trial. Adoption of this innovative approach in routine practice will depend on results of the larger multicentre trial that this feasibility study is designed to inform.


Research activity codes: 6.4 SURGERY
Health categories: CARDIOVASCULAR;RENAL AND UROGENITAL