Operating Room Air Filtration-Sterilization and Surgical Infections: The ORACLE Randomized Trial in 110,538 Surgeries

Background: Surgical infections are the most common nosocomial infections and cause substantial morbidity and mortality. Operating rooms are relatively clean, but far from sterile. An unknown fraction of infections result from wound contamination by air-borne bacteria. We therefore tested the hypothesis that supplemental air purification reduces wound infections and related complications. Methods: Operating rooms, our clusters, were each randomized in each 4-week blocks to either active or identical-looking sham supplemental air sterilization. All investigators, clinicians, and patients were fully blinded to treatment. No other aspect of anesthetic or surgical management was proscribed. Intent-to-treat analysis was restricted to adults who had surgery lasting at least an hour without evidence of pre-existing wound infections. We tested the primary hypothesis that supplemental active purification reduces a collapsed (one or more) composite of surgical wound infections, infection-related complications, or death within 30 days after inpatient surgery. Secondarily, we tested the hypothesis that supplemental air purification reduces the same composite after combined inpatient and outpatient surgeries. Results: A total of 110,538 combined inpatients and outpatients were enrolled across 68 operating rooms, with 107,334 qualifying for analysis. At the third interim analysis, the futility boundary on the composite outcome was crossed for inpatients and for all patients. Enrollment thus stopped with 58,938 randomized inpatients. The primary composite outcome occurred in 8.1% (n=2,389) of inpatients randomized to active purification versus 8.2% (n=2,405) with sham purification: odds ratio 0.98 (95%CI: 0.92 to 1.05), P=0.609. Across all patients, the secondary composite outcome occurred in 5.5% (n=2,959 / 53,730) of active purification cases versus 5.6% (n=2,981 / 53,604) sham cases: odds ratio 0.98 (95% CI: 0.93 to 1.05), P=0.669). Treatment effect did not vary over the weeks in the randomized periods. Conclusion: Supplemental active purification did not reduce surgical wound infections or mortality in surgical patients. Infection-control efforts might better focus on limiting direct wound contamination. Trial registration: A priori registration at ClinicTrials.gov: NCT04610294. Funding: Supported by a grant from ActivePure (Bristol, VA) to the Cleveland Clinic. The funder approved the original protocol which was written by the lead author. The funder was not involved in data acquisition, analysis, or manuscript preparation. A draft of the manuscript was provided to the funder as a courtesy.