Do the results of the OXYGEN trial change if analyzed as "as-treated?": A secondary analysis of the OXYGEN trial

Augustine M Saiz; Anthony R Carlini; Renan C Castillo; Manjari Joshi; Yanjie Huang; Clinton K Murray; Michael J Bosse; Arman Dagal; Joshua L Gary; Madhav A Karunakar; Michael J Weaver; William Obremskey; Todd O McKinley; Gregory T Altman; Jean-Claude G D'Alleyrand; Reza Firoozabadi; Susan C Collins; Julie Agel; Tara J Taylor; Alec C Stall; Ebrahim Paryavi; Nathan N O'Hara; Robert V O'Toole; Stephen J Warner; METRC

doi:10.1016/j.injury.2024.111953

Do the results of the OXYGEN trial change if analyzed as "as-treated?": A secondary analysis of the OXYGEN trial

Injury. 2024 Oct 13;55(12):111953. doi: 10.1016/j.injury.2024.111953. Online ahead of print.

Authors

Augustine M Saiz¹, Anthony R Carlini², Renan C Castillo², Manjari Joshi³, Yanjie Huang⁴, Clinton K Murray⁵, Michael J Bosse⁶, Arman Dagal⁷, Joshua L Gary⁸, Madhav A Karunakar⁶, Michael J Weaver⁹, William Obremskey¹⁰, Todd O McKinley¹¹, Gregory T Altman¹², Jean-Claude G D'Alleyrand¹³, Reza Firoozabadi¹⁴, Susan C Collins², Julie Agel¹⁴, Tara J Taylor², Alec C Stall¹⁵, Ebrahim Paryavi¹⁶, Nathan N O'Hara³, Robert V O'Toole¹⁷, Stephen J Warner¹⁸; METRC

Affiliations

¹ University of California, Davis, Sacramento, CA, USA.
² Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
³ University of Maryland School of Medicine, Baltimore, MD, USA.
⁴ University of Michigan, Ann Arbor, MI, USA.
⁵ Brooke Army Medical Center, Fort Sam Houston, TX, USA.
⁶ Atrium Health-Carolinas Medical Center, Charlotte, NC, USA.
⁷ University of Miami Ryder Trauma Center, Miami, FL, USA.
⁸ Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
⁹ Brigham and Women's Hospital and Massachusetts General Hospital at Harvard Medical School, Boston, MA, USA.
¹⁰ Vanderbilt University Medical Center, Nashville, TN, USA.
¹¹ Indiana University Health Methodist Hospital, Indianapolis, IN, USA.
¹² Allegheny General Hospital, Pittsburgh, PA, USA.
¹³ Landstuhl Regional Medical Center, Landstuhl, Germany.
¹⁴ University of Washington Medicine Harborview Medical Center, Seattle, WA, USA.
¹⁵ Nemours Children's Health, Orlando, FL, USA.
¹⁶ Alaska Native Medical Center, Anchorage, AK, USA.
¹⁷ University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: rotoole@som.umaryland.edu.
¹⁸ McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, USA.

PMID: 39442485
DOI: 10.1016/j.injury.2024.111953

Abstract

Objective: To determine if the results of the OXYGEN trial changed using an "as-treated" approach instead of the original "intention-to-treat" approach. The multi-center randomized controlled OXYGEN trial aimed to determine the effectiveness of high FiO2 in decreasing infection rates for high-risk tibial plateau, tibial pilon, and calcaneus fractures.

Methods: A secondary analysis of a multi-center randomized controlled trial conducted at 29 US trauma centers was performed. A total of 1231 patients aged 18-80 years with tibial plateau, tibial pilon, or calcaneus fractures thought to be at elevated risk of infection were enrolled. Patients were randomly assigned to receive inspired oxygen at a concentration of 80 % FiO2 (treatment) or 30 % FiO2 (control). Adherence was defined using two different criteria. Criterion 1 required at least 80 % of the surgery time ≤40 % FiO2 for the control group or ≥70 % FiO2 for the treatment group. Criterion 2 required at least 80 % of surgery time within 20-40 % (control) or 70-90 % FiO2 (treatment). The primary outcome was surgical site infection (SSI) within 182 days of definitive fracture fixation. Secondary outcomes were deep and superficial surgical site infections within 90, 182, and 365 days of definitive fixation.

Results: Under Criterion 1, the primary outcome occurred in 7 % (38/523) and 10 % (49/471) of patients in the treatment and control groups, respectively (p = 0.10). Deep infection occurred in 30 (6 %) treatment and 30 (6 %) control patients (p = 0.75). Superficial infection occurred in 9 (2 %) treatment and 20 (4 %) control patients (RR, 0.41; p = 0.03). Using Criterion 2, the primary outcome occurred in 7 % (36/498) of treatment and 10 % (48/468) of control patients (p = 0.12). Deep infection occurred in 28 (6 %) treatment and 29 (6 %) control patients (p = 0.81). Superficial infection occurred in 9 (2 %) treatment and 20 (4.3 %) control patients (RR = 0.43; p = 0.03).

Conclusions: When re-analyzing based on which patients actually received high or control levels of perioperative oxygen fraction, the results are somewhat consistent with the original "intent-to-treat" analysis. Specifically, high perioperative oxygen lowered the risk of superficial SSI but did not affect deep infections.

Keywords: Calcaneus fracture; Intent-to-treat; Perioperative inspiratory oxygen; Pilon; Surgical site infection; Tibial plateau.