Safety and Efficacy of TU-100 as an Adjunct to an Enhanced Recovery After Surgery in Subjects Undergoing Bowel Resection
- Registration Number
- NCT04742907
- Lead Sponsor
- Tsumura USA
- Brief Summary
This multicenter, randomized, double-blinded, placebo-controlled study will evaluate the effect of TU-100 on resolution of postoperative ileus (POI) in subjects undergoing open or laparoscopic bowel resection (BR).
- Detailed Description
Subjects will be screened up to 28 days before their planned surgery and will be randomized 1:1:1 (TU-100 15 g/day: TU-100 7.5 g/day: placebo) on postoperative Day 1 before the first dose of study medication. After randomization, subjects will receive a total daily dose of TU-100 15g, TU-100 7.5 g, 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 adjunct to an enhanced recovery (ERAS) pathway for gastrointestinal (GI) recovery.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 402
- Male or female ≥ 18 years of age
- Women of childbearing potential (WOCBP) or men whose sexual partners are WOCBP; must be able and willing to use at least 1 highly effective method of contraception during the study and for 30 days after the last dose of study drug
- American Society of Anesthesiologists Physical Status Score of 1 to 3
- Scheduled for an elective BR via open or laparoscopic approach
- Ability to understand the study procedures, have agreed to participate in the study program, and have voluntarily provided informed consent
- Scheduled for a BR that is not listed in this protocol
- Requires any additional resections beyond the intestine (eg, hepatectomy, distal pancreatectomy, pancreaticoduodenectomy, gastric resection, uterine resection), or concomitant surgeries (with the exception of biopsies)
- Requires the formation of a stoma (ileostomy or colostomy)
- History of surgeries, illness, or behavior (eg, depression, psychosis) that in the opinion of the investigator might confound the study results or pose additional risk in administering the study procedures
- Have a functional colostomy or ileostomy
- Diagnosed with advanced or metastatic colon cancer (Stage IV by tumor, node, and metastasis classification)
- Positive coronavirus disease 2019 (COVID-19) test
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (including human immunodeficiency virus (HIV)), diabetes, symptomatic congestive heart failure and ejection fraction < 35%, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with protocol requirements
- Chronic pain syndrome unrelated to the planned surgery requiring consistent management with analgesics and/or other non-pharmacologic modalities
- Myocardial infarction within 3 months
- Corrected QT interval > 500 msec
- Diabetic gastroparesis
- Compromised immune system, either from treatment with corticosteroids or other immunosuppressive agent within 2 weeks of surgery or from immunosuppressive disease (HIV)
- Pregnant (identified by a positive serum pregnancy test) or lactating, or are not postmenopausal (no menses for at least 1 year) and are of childbearing potential and not using an accepted method of birth control (surgical sterilization, intrauterine contraceptive device, oral contraceptive, diaphragm, or condom in combination with contraceptive cream, jelly, or foam or abstinence)
- Participated in another investigational drug/biologic or medical device study within 30 days of surgery or will be enrolled in another investigational drug or medical device study, or any study in which active subject participation is required outside routine hospital data collection during the course of the study
- Illicit drug use or alcohol abuse based on medical history, or currently engaged in illicit drug use or alcohol abuse
- Uses of supplemental ginger, ginseng, or Zanthoxylum fruit within 72 hours before randomization
- Has a history of allergic reactions to ginseng, ginger, Zanthoxylum fruit, or lactose
- Has clinical symptoms of lactose intolerance after ingesting milk or milk-containing products (abdominal pain, flatulence, diarrhea)
- Unwilling or unable to comply with procedures described in this protocol or is otherwise unacceptable for enrollment in the opinion of the investigator
- Has a history of previous surgeries, illness (interstitial pneumonia), or behavior (depression, psychosis) that, in the opinion of the investigator, might confound the study results or pose additional risk in administering the study procedures
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Subjects will receive placebo TID until hospital discharge or ≤ 10 days (whichever is earlier). TU-100 15 g/day TU-100 Subjects will receive a total daily dose of TU-100 5 g TID until hospital discharge or ≤ 10 days (whichever is earlier). TU-100 7.5 g/day TU-100 Subjects will receive a total daily dose of TU-100 2.5 g TID until hospital discharge or ≤ 10 days (whichever is earlier).
- Primary Outcome Measures
Name Time Method Time to Gastrointestinal Recovery (GIR) From the day after surgery (Day 1) until hospital discharge or Day 10 (whichever is earlier) Time to achieve recovery of GI motility as measured by a composite endpoint representing upper AND lower GI recovery
- Secondary Outcome Measures
Name Time Method Time to GIR Responses From the day after surgery (Day 1) until hospital discharge or Day 10 (whichever is earlier) Time to achieve first toleration of solid diet AND first bowel movement (Time to GI-2), time to first toleration of clear liquids, and time to absence of distension and presence of bowel sounds and flatus
Time to Discharge From surgery to hospital discharge Time at which the subject is considered ready for discharge by the investigator based solely on GI recovery (Time to ready for discharge), and time at which the investigator writes discharge order for the subject (Time to discharge order written)
GIR Outcome Related to Length of Hospitalization (Mean) From surgery to hospital discharge Mean number of days that the subject stayed in the hospital calculated based on calendar day of discharge order written
GIR Outcome Related to Length of Hospitalization (Median) From surgery to hospital discharge Median number of days that the subject stayed in the hospital calculated based on calendar day of discharge order written
Percentage of GIR Responders From the day after surgery (Day 1) until hospital discharge or Day 10 (whichever is earlier) Percentage of subjects who achieve GIR (GIR responders) by day
POI-related Morbidity From the day after surgery to discharge follow-up visit (30 days (+ 15 days) after hospital discharge) Primary POI that is not secondary to surgical complication, such as anastomotic leak, abscess formation, or sepsis that requires readmission within 7 days of discharge, or need for postoperative nasal gastric tube insertion to manage symptoms of POI (vomiting/retching, abdominal distension)
Number of Participants With Adverse Events From baseline to discharge follow-up visit (30 days (+ 15 days) after hospital discharge) Number of patients with adverse events (AEs) observed following administration of TU-100.
Trial Locations
- Locations (36)
Florence Site
🇺🇸Florence, Alabama, United States
Little Rock Site
🇺🇸Little Rock, Arkansas, United States
Duarte Site
🇺🇸Duarte, California, United States
Palo Alto Site
🇺🇸Palo Alto, California, United States
Clearwater Site
🇺🇸Clearwater, Florida, United States
Weston Site
🇺🇸Weston, Florida, United States
Urbana Site
🇺🇸Urbana, Illinois, United States
Lexington Site
🇺🇸Lexington, Kentucky, United States
Metairie Site
🇺🇸Metairie, Louisiana, United States
St. Louis Site
🇺🇸Saint Louis, Missouri, United States
Newark Site
🇺🇸Newark, New Jersey, United States
Mineola Site
🇺🇸Mineola, New York, United States
New York Site
🇺🇸New York, New York, United States
Stony Brook Site
🇺🇸Stony Brook, New York, United States
Cleveland Site #2
🇺🇸Cleveland, Ohio, United States
Philadelphia Site #2
🇺🇸Philadelphia, Pennsylvania, United States
Memphis Site
🇺🇸Memphis, Tennessee, United States
Charleston Site
🇺🇸Charleston, South Carolina, United States
Fort Worth Site
🇺🇸Fort Worth, Texas, United States
Roanoke Site
🇺🇸Roanoke, Virginia, United States
Gilbert Site
🇺🇸Gilbert, Arizona, United States
Cleveland Site #1
🇺🇸Cleveland, Ohio, United States
Pittsburgh Site
🇺🇸Pittsburgh, Pennsylvania, United States
Los Angeles Site #1
🇺🇸Los Angeles, California, United States
Danbury Site
🇺🇸Danbury, Connecticut, United States
Dallas Site
🇺🇸Dallas, Texas, United States
Los Angeles Site #2
🇺🇸Los Angeles, California, United States
Chicago Site #2
🇺🇸Chicago, Illinois, United States
Chicago Site #1
🇺🇸Chicago, Illinois, United States
Boston Site #1
🇺🇸Boston, Massachusetts, United States
Salt Lake City Site
🇺🇸Salt Lake City, Utah, United States
Detroit Site
🇺🇸Detroit, Michigan, United States
Milwaukee Site
🇺🇸Milwaukee, Wisconsin, United States
Tampa Site
🇺🇸Tampa, Florida, United States
Sacramento Site
🇺🇸Sacramento, California, United States
Orlando Site
🇺🇸Orlando, Florida, United States