548. A Randomized, Double-blind, Controlled Trial of Vancomycin Taper/Pulse and Fidaxomicin compared to Vancomycin for Treatment of a First or Second Recurrence of Clostridioides difficile Infection

Abstract Background Vancomycin taper followed by pulse and fidaxomicin are two common treatments for recurrent C. difficile infection (rCDI) but they have not been formally compared.Kaplan-Meier plot of days from symptom resolution to recurrences of diarrhea [A] and recurrent C. difficile infection (rCDI) [B] in the modified intent-to-treat population. Methods We conducted a randomized, double-blind trial of vancomycin taper and pulse (VAN-TP, 125 mg four times daily for 10d, followed by a once daily, once every other day, and once every third day, each for 7 days) and fidaxomicin (FDX, 200 mg twice daily for 10d) compared to vancomycin (VAN, 125 mg four times daily for 10d) for patients with a first or second rCDI episode. The primary study endpoint was sustained clinical response (SCR) at day 59 using a diarrhea composite outcome (D-COM) in modified intent to treat analysis (mITT). Secondary outcomes included SCR without rCDI (CDI-COM), diarrhea resolution at day 10, recurrent diarrhea and rCDI. Results 308 participants were randomized to 1 of the 3 arms. Sustained D-COM was higher for VAN-TP (58.6%) than for VAN (44.1%) at day 59 (Unadjusted P=0.04, Z-statistic scores at 2.03-2.08, efficacy boundary 2.234 controlling the FWER at 0.05, mITT). Sustained CDI-COM was also higher for VAN-TP (64.8%) than for VAN (48.4%) (P=0.05). There was no difference in D-COM or CDI-COM at day 59 between FDX and VAN (D-COM: 44.1% vs. 44.1%, P=1.00; CDI-COM: 51.8% vs. 48.4%, P=0.86). Symptom resolution by day 10 was greater than 90% for all three groups. CDI recurrence, but not diarrhea recurrence was less common in VAN-TP than in VAN at day 59 (rCDI: 26.6% versus 43.6%, P=0.05; diarrhea recurrence: 34.1% vs. 49.4%, P=0.08). Survival estimates for days from symptom resolution to diarrhea recurrence (Fig A) and CDI recurrence (Fig B) show separation by day 20 which continues to day 90 for VAN-TP compared to VAN. Conclusion A tapered and pulsed regimen of vancomycin following a standard treatment course was superior to a standard course of vancomycin for sustained resolution of diarrhea and CDI at day 59 in patients with recurrent CDI. A standard course of fidaxomicin was not different from a standard course of vancomycin in this population. Disclosures All Authors: No reported disclosures