Vancomycin Taper Trial Finds Mixed Cdi Recurrence Signal

Key Takeaways

• Lower recurrence was observed with the taper regimen at day 38, while the day 56 primary comparison was closer and carried a 73.8% posterior probability of superiority.
• All participants received 14 days of oral vancomycin 125 mg four times daily before randomization on day 15 to taper dosing or matched placebo capsules.
• Adverse effects were uncommon in both groups, and the timing pattern left open the possibility that some recurrences were delayed rather than prevented.

A 4-week vancomycin pulse-and-taper schedule was associated with lower CDI recurrence at day 38 than the 2-week comparison regimen, 6.7% versus 15.4%. In a double-blind randomized trial across 12 Canadian hospitals, 265 adults with a first episode or first recurrence entered the analysis. Investigators compared taper dosing with matched placebo capsules after a standardized vancomycin run-in. The separation was more pronounced earlier in follow-up than at the primary day 56 comparison.

Adults aged 18 years or older were eligible if they had a first episode or first recurrence of CDI with clinical disease and laboratory confirmation. Enrollment also required improvement by day 10, and 265 participants were included in the analysis after withdrawals. All participants received oral vancomycin 125 mg four times daily for 14 days before day 15 randomization to taper dosing or matched placebo capsules with blinded dispensing. The primary recurrence window was days 15 to 56, and the main analysis used a Bayesian framework. Participants had weekly contact through day 56 and then follow-up every 2 weeks until day 90.

By day 56, recurrence occurred in 20 of 135 patients, or 14.8%, in the taper group and 23 of 130, or 17.7%, in the comparison group. The adjusted relative risk was 0.84 with a 95% credible interval of 0.48 to 1.45, and the posterior probability of superiority was 73.8%. At day 38, recurrence was 9 of 135, or 6.7%, versus 20 of 130, or 15.4%. The adjusted relative risk was 0.43, with a 95% CrI of 0.19 to 0.89, and the posterior probability of superiority was 99.0%. A restricted mean survival time analysis favored tapering by 2.19 days, consistent with earlier divergence in recurrence timing rather than established prevention.

By day 90, recurrence was 23 of 135, or 17.0%, in the taper group and 24 of 130, or 18.5%, in the comparison group. The adjusted relative risk at that point was 0.92 with a 95% CrI of 0.54 to 1.56, with less separation between groups. Most recurrences occurred within the first 2 weeks after vancomycin stopped, and exploratory subgroup analyses were generally aligned with the overall pattern. Any adverse effect occurred in 15 of 132 patients, or 11.4%, versus 13 of 129, or 10.1%. Study drug was stopped because of adverse effects in 2 of 132 patients, or 1.5%, versus 3 of 129, or 2.3%. No colectomies or fecal microbiota transplants were reported by day 90, and adverse effects were uncommon in both groups.

The pattern across day 38, day 56, and day 90 raised the possibility that some recurrences were delayed rather than prevented. The day 56 posterior probability remained below the prespecified superiority threshold in the Bayesian design. Recruitment became infeasible and event rates were lower than anticipated, so the trial stopped early, reducing power and limiting certainty around the primary comparison.

Overall, the regimen appeared to shift recurrence timing more clearly than recurrence frequency by the end of follow-up.