A trial of in-hospital, electronic alerts for acute kidney injury: design and rationale

Abstract

Background: Acute kidney injury is common in hospitalized patients, increases morbidity and mortality, and is under-recognized. To improve provider recognition, we previously developed an electronic alert system for acute kidney injury. To test the hypothesis that this electronic acute kidney injury alert could improve patient outcome, we designed a randomized controlled trial to test the effectiveness of this alert in hospitalized patients. The study design presented several methodologic, ethical, and statistical challenges.

Purpose: To highlight the challenges faced and the solutions employed in the design and implementation of a clinical trial to determine whether the provision of an early electronic alert for acute kidney injury would improve outcomes in hospitalized patients. Challenges included how to randomize the delivery of the alert system and the ethical framework for waiving informed consent. Other methodologic challenges included the selection and statistical evaluation of our study outcome, a ranked-composite of a continuous covariate (creatinine) and two dichotomous outcomes (dialysis and death), and the use of the medical record as a source of trial data.

Methods: We have designed a randomized trial to assess the effectiveness of an electronic alert system for acute kidney injury. With broad inclusion criteria, and a waiver of informed consent, we enroll and randomize virtually every patient with acute kidney injury in our hospital.

Results: As of 31 March 2014, we have enrolled 2373 patients of 2400 targeted. Pre-alert data demonstrated a strong association between severity of acute kidney injury and inpatient mortality with a range of 6.4% in those with mild, stage 1 acute kidney injury, to 29% among those with stage 3 acute kidney injury (p < 0.001). We judged that informed consent would undermine the scientific validity of the study and present harms that are out of proportion to the very low risk intervention.

Conclusion: Our study demonstrates the feasibility of designing an ethical randomized controlled trial of an early electronic alert for acute kidney injury without obtaining informed consent from individual participants. Our study outcome may serve as a model for other studies of acute kidney injury, insofar as our paradigm accounts for the effect that early death and dialysis have on assessment of acute kidney injury severity as defined by maximum achieved serum creatinine.

Trial registration: ClinicalTrials.gov NCT01862419.

Keywords: Acute kidney injury; acute renal failure; composite outcomes; ethics; waiver of informed consent.

© The Author(s) 2014.

Figures

Figure 1. Time-Course of Study Entry

Three patients who meet criteria for Acute Kidney Injury (AKI) on day 4. –Patient 1 by 50% increase in serum creatinine over ≤7 days, Patient 2 by 0.3 mg/dL increase in serum creatinine increase over ≤48 hours, and Patient 3 by both criteria. Assessment of the combined primary outcome is limited to the 7 days after meeting AKI criteria.

Figure 2. Schema of our rank-based composite endpoint

Participants are ranked initially based on peak relative change in serum creatinine concentration. At the end of 7 days, the outcome for patients who received dialysis but have not died is ranked worse than all patients who neither received dialysis nor died. The outcome for patients who died is ranked worst.