Abstract
Introduction
Very few burn care interventions have been rigorously evaluated with adequately powered randomized clinical trials (RCTs) focusing on long-term clinically relevant outcomes. There is a need to improve the efficiency of RCTs in burn care so that more definitive high quality RCTs can be completed with the available resources. Persistent Organ Dysfunction (POD) plus death is a novel endpoint that has been previously validated in general ICU patients. The objective of this study was to validate and demonstrate the utility of POD+death for clinical trials of burn patients.
Methods
We performed a secondary analysis of a dataset from a RCT of enteral glutamine (the RE-ENERGIZE Trial) involving 60 Intensive Care Units (ICUs) around the world. Enrolled patients were followed for 6 months documenting hospital and 6 months outcomes including quality of life. For the purposes of this analysis, we restricted inclusion to patients with >20% burn size. We define POD as requiring supportive technologies during critical illness and is present when a patient has ongoing requirement for vasopressors, dialysis, or mechanical ventilation at the outcome assessments time points. We evaluated the data for the prevalence of POD and its association with outcome. We hypothesized that patients alive with POD, compared to those alive without POD, would have worse clinical outcomes and that by combining POD+death, we would gain statistical efficiencies.
Results
Five hundred thirty-nine patients were involved in this analysis. At 28 days, 4.6% of patients were estimated to have circulatory failure, 6.3% had renal failure, 17.1% had respiratory failure, and 8.9% had died, for an overall prevalence of POD+death=27%. Of survivors at day 28, those with POD, compared to those without POD, had a higher mortality rate in the follow up period, had longer ICU and hospital stays, and a reduced quality of life on many of the domains at 6 months (see Tables). Using our observed 28 day rates, to achieve 80% power at a two-sided alpha=0.05 to determine a 25% RRR in mortality, we would require 2246 patient per group to detect a 25% RRR in mortality from 9% to 6.75%, but only 573 patients per group to detect a 25% RRR in mortality+POD from 27% to 20%
Conclusions
POD+death may be a valid composite outcome measure and compared to historically used endpoints, POD may reduce the sample size requirements of clinical trials of severe burns patients. Further validation in larger clinical trials is required.
Applicability of Research to Practice
To improve the efficiency of RCTs in burn settings.
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