Delay in GI Recovery/Postoperative Ileus (POI)
Conditions
Keywords
TU-100, Daikenchuto, Kampo Medicine, Enhanced Recovery After Surgery, ERAS, Postoperative Ileus, Gastrointestinal Recovery, Radical Cystectomy, Complex Abdominal Wall Reconstruction, Abdominal Surgery, Major Abdominopelvic Surgery
Brief summary
This Phase 2, multicenter, randomized, double-blind, placebo-controlled master protocol study will evaluate the safety and efficacy of TU-100, adjunctive to an Enhanced Recovery After Surgery (ERAS) pathway, for accelerating gastrointestinal recovery following major abdominopelvic surgery. TU-100 will be evaluated in 2 surgical populations under a Master Protocol: 1. Subjects undergoing Radical Cystectomy (RC), 2.subjects undergoing Complex Abdominal Wall Reconstruction (CAWR).
Detailed description
Subjects will be screened for eligibility up to 28 days before their planned RC or CAWR surgery and will be randomized 1:1 (TU-100 7.5 g/day: placebo) on postoperative Day 1 before the first dose of study medication. After randomization, subjects will receive TU-100 7.5 g/day or matching placebo (3 times per day (TID)) until hospital discharge or ≤ 10 days (whichever is earlier). All subjects will be treated with study medication as adjunctive to an Enhanced Recovery After Surgery (ERAS) pathway for gastrointestinal recovery. The primary objective of the study is to compare the effect of TU-100 with placebo, in conjunction with and ERAS pathway, on the proportion of subjects achieving confirmed upper and lower GI recovery (GIR) following major abdominopelvic surgery requiring extensive manipulation and/or resection of the bowel.
Interventions
DRUGTU-100
TU-100 is a traditional Japanese herbal medicine consisting of processed ginger, ginseng, and Japanese pepper (Zanthoxylum fruit). Participants will receive 7.5 g/day orally administered as 2.5 g three times daily.
DRUGPlacebo
Matching placebo granules similar in appearance to TU-100 and administered orally three times daily.
Sponsors
Tsumura USA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Participants, investigators, study staff, sponsor designees, clinical endpoint adjudication committee (CEAC), and study treatment administrators will remain blinded to treatment assignment. Participants will be randomized 1:1 to receive TU-100 7.5 g/day or matching placebo. An independent statistical group supporting DSMB reviews will be unblinded. Emergency unblinding is permitted when required for subject safety.
Intervention model description
This Phase 2 multicenter master protocol consists of two parallel sub-studies in subjects undergoing Radical Cystectomy (RC) or Complex Abdominal Wall Reconstruction (CAWR). Within each sub-study, eligible participants will be randomized 1:1 on postoperative Day 1 to receive TU-100 7.5 g/day or matching placebo. Aanalyses will be performed for each sub-study individually and for key outcomes for the pooled sub-studies.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female participants aged 18 years or older * American Society of Anesthesiologists (ASA) Physical Status Classification I-III * Scheduled to undergo elective open or minimally invasive Radical Cystectomy (RC) with continent or incontinent urinary diversion requiring bowel resection, or open or complex minimally invasive surgery for Complex Abdominal Wall Reconstruction (CAWR) with anticipated myofascial advancement flap and mesh placement for moderate or giant hernia defects * Body mass index (BMI) ≤40 kg/m² * Women of childbearing potential and men with partners of childbearing potential must agree to use highly effective contraception * Willing and able to comply with study procedures and able to voluntarily provide informed consent
Exclusion criteria
* Not scheduled for a Radical Cystectomy (RC) or Complex Abdominal Wall Reconstruction (CAWR) procedure meeting the inclusion criteria * Known gastric or bowel obstruction * Have had or have planned gastrectomy, gastric bypass, colostomy, or ileostomy * Significant gastrointestinal motility disorders * Pregnancy or breastfeeding * Clinically significant hepatic, renal, cardiovascular, or other uncontrolled medical conditions * Immunocompromised state or recent immunosuppressive therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Confirmed Gastrointestinal Recovery (GIR) Response by postoperative day (POD) 3 | Postoperative Day 3 | Proportion of subjects achieving gastrointestinal recovery (\[first toleration of solids\] and \[first spontaneous bowel movement or 1st consistent flatus\]; GIR) by POD 3 without a subsequent serious adverse event (SAE) of primary POI. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Confirmed GI-2 Recovery Response by POD 4 | Postoperative Day 4 | Proportion of subjects achieving first toleration of solids and first spontaneous bowel movement (GI-2 recovery) by POD 4 without a subsequent SAE of primary POI. |
| Time to Gastrointestinal Recovery (GIR) | From the day of surgery (Day -1) through hospital discharge or Day 10, whichever occurs first | Time from the end of surgery to confirmed GIR, defined as first toleration of solid food and first spontaneous bowel movement or first consistent flatus. |
| Proportion of subjects who achieve confirmed GIR by each postoperative day | Postoperative Days 1-10 | Percentage of subjects achieving confirmed GIR, defined as first toleration of solid food and first spontaneous bowel movement or first consistent flatus, without a subsequent SAE of primary POI. |
| Time to GI-2 Recovery | From the day of surgery (Day -1) through hospital discharge or Day 10, whichever occurs first | Time from the end of surgery to GI-2 recovery, defined as first toleration of solid food and first spontaneous bowel movement. |
| Proportion of subjects who achieve GI-2 recovery by each postoperative day | Postoperative Days 1-10 | Percentage of subjects achieving GI-2 recovery, defined as first toleration of solid food and first spontaneous bowel movement. |
| Length of Hospital Stay | From the day of surgery (Day -1) through hospital discharge or Day 10, whichever occurs first | Length of hospital stay measured as the number of calendar days from the day of surgery to the date of hospital discharge. |
| Occurrence of Nausea, Vomiting and/or Retching, and Abdominal Bloating | Postoperative Days 1-10 | Proportion of subjects reporting nausea, vomiting and/or retching, and abdominal bloating during postoperative recovery. Data will be collected using subject-reported assessments and summarized by postoperative day. |
| Bothersomeness of Nausea and Abdominal Bloating | Postoperative Days 1-10 | Subject-reported bothersomeness of nausea and abdominal bloating (24-hour reflection) during postoperative recovery. Data will be collected using subject-reported assessments and summarized by postoperative day. Bothersomeness is measured on a 0-10 point scale with 10 being the most bothersome. |
| Average of Abdominal Pain | Postoperative Days 1-10 | Subject-reported abdominal pain (24-hour reflection) during postoperative recovery. Data will be collected using subject-reported assessments and summarized by postoperative day. Average abdominal pain will be reported on a 11-point Numeric Pain Rating Scale (NPRS), with 0 being no pain and 10 being worst pain imaginable. |
| Time to ready for discharge | From the day of surgery (Day -1) through hospital discharge or Day 10, whichever occurs first | Time from the end of surgery to readiness for discharge, based solely on GI recovery. |
| Time to discharge order written | From the day of surgery (Day -1) through hospital discharge or Day 10, whichever occurs first | Time from the end of surgery to discharge order entry. |
| Time to actual hospital discharge | From the day of surgery (Day -1) through hospital discharge or Day 10, whichever occurs first | Time from the end of surgery to actual hospital discharge. |
| Time to first consistent flatus | From the day of surgery (Day -1) through hospital discharge or Day 10, whichever occurs first | Time from the end of surgery to first consistent flatus. |
| Time to First Spontaneous Bowel Movement | From the day of surgery (Day -1) through hospital discharge or Day 10, whichever occurs first | Time from the end of surgery to the first spontaneous bowel movement. |
| Time to Toleration of Solid Food | From the day of surgery (Day -1) through hospital discharge or Day 10, whichever occurs first | Time from the end of surgery to the first toleration of solid food without clinically significant intolerance requiring cessation of oral intake. |
Contacts
CONTACTTomoyuki Hashiguchi, Director, Clinical Development
STUDY_DIRECTORTomoyuki Hashiguchi, Director, Clinical Development
Tsumura USA
Outcome results
None listed