Evaluation of TU-100 (Daikenchuto), a Traditional Japanese Kampo Medicine, As an Adjunct to Enhanced Recovery After Surgery, for Acceleration of Gastrointestinal Recovery After Bowel Resection - Results of a Proof-of-Concept, Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial.

Abstract

Background: A transient inhibition of gastrointestinal motility (postoperative ileus) can occur after colorectal surgery and may lead to complications and prolonged hospitalization.

Objective: To examine the effect of TU-100, Japanese herbal medicine, on acceleration of gastrointestinal recovery after bowel resection.

Design: Proof-of-concept, randomized, double-blind, placebo-controlled Phase 2 trial (NCT04742907).

Settings: Thirty-six United States hospital sites.

Patients: Patients undergoing elective bowel resection.

Interventions: Placebo, TU-100 7.5g/day, or TU-100 15 g/day orally from postoperative day 1 for ≤10 days while hospitalized.

Main outcome measures: The primary endpoint was time to gastrointestinal recovery, a composite representing upper (first toleration of clear liquids) and lower ([first bowel movement] or [absence of distension and presence of bowel sounds and flatus]) gastrointestinal motility. Multiple gastrointestinal- and discharge-related outcomes were also evaluated.

Results: A total of 392 patients received ≥1 dose. TU-100 7.5 g/day was not associated with a statistically significant difference for gastrointestinal recovery (hazard ratio = 1.17 [95% CI: 0.91, 1.50]). But a higher proportion of patients in the 7.5 g/day group achieved gastrointestinal recovery by postoperative day 2 vs placebo (78.1% vs 66.9%, p = 0.047). Median length of stay was significantly shorter in the 7.5 g/day (2 days) vs placebo (3 days [p = 0.03]). Patient-reported nausea and abdominal bloating bothersomeness were lower in the early postoperative period for 7.5 g/day vs placebo. Overall, no significant differences between 15 g/day and placebo were noted.

Limitations: Limited dosing and short evaluation window (short hospital stay).

Conclusions: Compared with placebo, TU-100 7.5 g/day was associated with consistent, encouraging trends for efficacy outcomes, including more patients achieving gastrointestinal recovery by postoperative day 2 with less bothersome gastrointestinal symptoms. A statistically significant difference in hospital stay for 7.5 g/day vs placebo was noted despite relatively short stays, drug administration not begun until postoperative day 1, and use with enhanced recovery after surgery pathways. Further studies are warranted. See Video Abstract.