Uso del Ensayo Clínico de Terapia Antimicrobiana Oral versus Parenteral (COPAT) para Influir en la Transformación de...

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 impact of early oral transition in a real-world setting and studied its influence on practice transformation.

C omparing Oral vs. Parenteral Antimicrobial Therapy (COPAT) Trial was a pragmatic, randomized controlled trial at five hospitals in one rural health system. Patients requiring two or more weeks of IV antibiotics (for all but central nervous system infections) were randomized 2:1 to Experimental (early oral) vs. Control (IV-only). Two primary outcomes and hypotheses were assessed at three months: early oral group safety superiority and efficacy equivalence. Clinical cases of patients who completed the trial were presented at multiple forums.

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% vs. 6.5%, p= 0.02). Lower cumulative hazard for first study related adverse event in early oral group (HR 0.24, 95% CI 0.08-0.75, p= 0.01) appeared to emerge by day 10. Therapeutic efficacy was equivalent. Cumulative enrollment in the trial had a significant association with COpAT:OPAT program consult ratio (R2= 0.54, p< 0.001).

Early oral antibiotic transition was significantly safer. At our academic health system, implementation of the COPAT Trial accelerated practice transformation.