A3(T)
TRIAL ANNOUNCEMENT. INTRODUCING ‘ERICCA’: A MULTI-CENTRE,
RANDOMISED, DOUBLE-BLINDED, CONTROLLED CLINICAL TRIAL ON THE
EFFECT OF REMOTE ISCHAEMIC PRECONDITIONING ON CLINICAL
OUTCOMES (INCLUDING ACUTE KIDNEY INJURY) IN PATIENTS UNDERGOING
CORONARY ARTERY BYPASS GRAFT SURGERY
Candillo, L1. Laing, C2, Kunst, G3, Pepper, J4, Kolvekar, S5, Knight, R6, Ariti, C6,
Clayton, T6, Yellon, D1, Hausenloy, D1 (on behalf of the ERICCA investigators)
1
The Hatter Cardiovascular Insititute, University College London, 2UCL Centre for
Nephrology Royal Free, London, 3King’s College London, London, 4Royal Brompton
Hospital, London, 5The Heart Hospital, University College London Hospitals, London,
6
Clinical Trials Unit, London School of Hygiene and Tropical Medicine, London
BACKGROUND: Novel cardioprotective strategies are required to improve clinical outcomes
including acute kidney injury (AKI) in high-risk patients undergoing coronary artery bypass
graft (CABG) ±valve surgery. Remote ischemic pre-conditioning (RIC), in which brief episodes
of ischemia and reperfusion are applied to the arm, has been demonstrated to reduce myocardial
injury during CABG ±valve surgery. We have also published pilot data suggesting a reduction
in AKI in this context. We are to formally investigate whether RIC can improve clinical
outcomes in the ERICCA trial (Effect of Remote Ischemic preConditioning on clinical
outcomes in patients undergoing Coronary Artery Bypass Graft surgery. ClinicalTrials.gov
Identifier: NCT01247545).
OBJECTIVES: The primary objective of the study is to determine if RIC improves one year
cardiovascular clinical outcomes (CV death, non-fatal myocardial infarction, revascularisation
and stroke), acute kidney injury, development of CKD at 1 year, myocardial injury (assessed by
troponin rise), inpatient morbidity (ITU stay, inotrope score, 6-minute walk test, and quality of
life) and LV function in patients undergoing high-risk cardiac (CABG+/-valve) surgery.
STUDY DESIGN: This is a randomised, double-blind, placebo controlled trial and will recruit
1610 patients. The study has been funded by NIHR and The British Heart Foundation.
Inclusion criteria are age>18, cardiac surgery with cold-blood cardioplegia and Euroscore of
perioperative risk greater than or equal to 6. Exclusion criteria include eGFR<30.
Randomisation will ocurr to RIC or sham-RIC. Radnomisation will be controlled centrally by
the Clinical Trials Unit, London School of Hygiene and Tropical Medicine. RIC will be
performed post-anaesthesia. Renal evaluation will be through AKI score (AKIN classification)
with serum creatinine at baseline, daily postoperative, 6 weeks and 12 months. A 24hour area
under the curve serum NGAL measurement will be done with NGAL measurements at baseline,
6, 12 and 24 hours post-pump. Samples for genomic metabolic and proteomic analyses will be
taken and stored.
IMPLICATIONS: Acute kidney injury (AKI) is common in cardiac surgery and even mild
forms of AKI confer considerable increases in mortality in this scenario. Severe AKI is one of
the most reliable predictors of postoperative death. If RIC reduces AKI in cardiac surgery this
will not improve outcomes in such cardiac patients but may have applications in other AKI
scenarios. ERICCA will be one of the largest prospective studies investigating AKI after
cardiac surgery. It will also be one of the largest studies examining NGAL biomarker
performance in AKI and CKD prediction in this context. As regards the RIC intervention,
ERICCA will be the largest AKI prevention study yet undertaken through a formal randomised,
controlled trial.