Early-oral antibiotics showed safety superiority and efficacy equivalence versus IV-only in patients requiring prolonged therapy

BACKGROUND: Extensive literature has established equivalent efficacy of early intravenous (IV) to oral antibiotic transition. However, there is variability in adoption across practice settings. Unlike Outpatient Parenteral Antimicrobial Therapy (OPAT) programs, Complex Outpatient Antimicrobial Therapy with Oral Agents (COpAT) programs face significant implementation science challenges. We used a clinical trial with broad enrollment criteria to determine the impact of early oral transition in a real-world setting and studied its influence on practice transformation. METHODS: Comparing Oral versus Parenteral Antimicrobial Therapy (COPAT) Trial was a pragmatic, randomized controlled trial at 5 hospitals in 1 rural health system. Patients who required 2 or more weeks of IV antibiotics (for all but central nervous system infections) were randomized 2:1 to experimental (early-oral) group or control (IV-only) group. Two primary outcomes and hypotheses were assessed at 3 months: early-oral group safety superiority and efficacy equivalence. Clinical cases of patients who completed the trial were presented at multiple forums. RESULTS: The trial was stopped early after two-thirds enrollment for a significant safety benefit. Early-oral group demonstrated a significantly lower adverse event rate (3.2% versus 6.5%, P = .02). Lower cumulative hazard for first study-related adverse event in early-oral group (hazard ratio, 0.24; 95% confidence interval, .08-.75; P = .01) appeared to emerge by day 10. Therapeutic efficacy was equivalent. Cumulative enrollment in the trial had a significant association with the COpAT:OPAT program consult ratio (R2= 0.54, P < .001). CONCLUSIONS: Early oral antibiotic transition was significantly safer. At our academic health system, implementation of the COPAT Trial accelerated practice transformation. CLINICAL TRIALS REGISTRATION: NCT05977868.