Biomarker-guided intervention to prevent acute kidney injury after major surgery (BigpAK-2 trial): study protocol for an international, prospective, randomised controlled multicentre trial

Abstract

IntroductionPrevious studies demonstrated that the implementation of the Kidney Disease Improving Global Outcomes (KDIGO) guideline-based bundle, consisting of different supportive measures in patients at high risk for acute kidney injury (AKI), might reduce rate and severity of AKI after surgery. However, the effects of the care bundle in broader population of patients undergoing surgery require confirmation.Methods and analysisThe BigpAK-2 trial is an international, randomised, controlled, multicentre trial. The trial aims to enrol 1302 patients undergoing major surgery who are subsequently admitted to the intensive care or high dependency unit and are at high-risk for postoperative AKI as identified by urinary biomarkers (tissue inhibitor of metalloproteinases 2*insulin like growth factor binding protein 7 (TIMP-2)*IGFBP7)). Eligible patients will be randomised to receive either standard of care (control) or a KDIGO-based AKI care bundle (intervention). The primary endpoint is the incidence of moderate or severe AKI (stage 2 or 3) within 72 hours after surgery, according to the KDIGO 2012 criteria. Secondary endpoints include adherence to the KDIGO care bundle, occurrence and severity of any stage of AKI, change in biomarker values during 12 hours after initial measurement of (TIMP-2)*(IGFBP7), number of free days of mechanical ventilation and vasopressors, need for renal replacement therapy (RRT), duration of RRT, renal recovery, 30-day and 60-day mortality, intensive care unit length-of-stay and hospital length-of-stay and major adverse kidney events. An add-on study will investigate blood and urine samples from recruited patients for immunological functions and kidney damage.Ethics and disseminationThe BigpAK-2 trial was approved by the Ethics Committee of the Medical Faculty of the University of Münster and subsequently by the corresponding Ethics Committee of the participating sites. A study amendment was approved subsequently. In the UK, the trial was adopted as an NIHR portfolio study. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and will guide patient care and further research.Trial registration numberNCT04647396.

Toward Precision Medicine: Exploring the Landscape of Biomarkers in Acute Kidney Injury

“…Although overall AKI rates did not differ, episodes of moderate and severe AKI, ICU length, and hospital stay were significantly lower in the controlled group [79]. This study led to the initiation of the BigpAK-2, an international multi-center prospective randomized controlled trial expected to enroll 1302 patients to retest the primary outcome in a broader population [80].…”

Future Directions in Optimizing Anesthesia to Reduce Perioperative Acute Kidney Injury

“…The biomarker-guided KDIGO bundle has been shown in previous Prev-AKI trials to be effective in reducing AKI in cardiac surgery patients [121, 122]. Moreover, multiple BIGPAC trials have shown that early biomarker-based prediction of AKI after implementation of the KDIGO care package reduces the risk of postoperative AKI [123, 124]. Anesthetics can improve the level of traditional biomarkers, while the new biomarkers applied by care bundle can be diagnosed earlier.…”