Clinical trial NCT04742907: Safety and Efficacy of TU-100 as an Adjunct to an Enhanced Recovery After Surgery in Subjects Undergoing Bowel Resection
Official title: Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial to Evaluate the Safety and Efficacy of TU-100 as an Adjunct to an Enhanced Recovery After Surgery (ERAS) Protocol in Subjects Undergoing Bowel Resection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Enhanced Recovery After Surgery
Lead sponsor: Tsumura USA
Sponsor class: INDUSTRY
First posted: 2021-02-08
Enrollment: 402
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, Double-Blind, Placebo-Controlled
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Male or female ≥ 18 years of age
2. 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
3. American Society of Anesthesiologists Physical Status Score of 1 to 3
4. Scheduled for an elective BR via open or laparoscopic approach
5. Ability to understand the study procedures, have agreed to participate in the study program, and have voluntarily provided informed consent

Exclusion Criteria:

1. Scheduled for a BR that is not listed in this protocol
2. Requires any additional resections beyond the intestine (eg, hepatectomy, distal pancreatectomy, pancreaticoduodenectomy, gastric resection, uterine resection), or concomitant surgeries (with the exception of biopsies)
3. Requires the formation of a stoma (ileostomy or colostomy)
4. 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
5. Have a functional colostomy or ileostomy
6. Diagnosed with advanced or metastatic colon cancer (Stage IV by tumor, node, and metastasis classification)
7. Positive coronavirus disease 2019 (COVID-19) test
8. 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
9. Chronic pain syndrome unrelated to the planned surgery requiring consistent management with analgesics and/or other non-pharmacologic modalities
10. Myocardial infarction within 3 months
11. Corrected QT interval \> 500 msec
12. Diabetic gastroparesis
13. Compromised immune system, either from treatment with corticosteroids or other immunosuppressive agent within 2 weeks of surgery or from immunosuppressive disease (HIV)
14. 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)
15. 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
16. Illicit drug use or alcohol abuse based on medical history, or currently engaged in illicit drug use or alcohol abuse
17. Uses of supplemental ginger, ginseng, or Zanthoxylum fruit within 72 hours before randomization
18. Has a history of allergic reactions to ginseng, ginger, Zanthoxylum fruit, or lactose
19. Has clinical symptoms of lactose intolerance after ingesting milk or milk-containing products (abdominal pain, flatulence, diarrhea)
20. Unwilling or unable to comply with procedures described in this protocol or is otherwise unacceptable for enrollment in the opinion of the investigator
21. 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

Primary outcomes:
measure: Time to Gastrointestinal Recovery (GIR)
timeFrame: From the day after surgery (Day 1) until hospital discharge or Day 10 (whichever is earlier)
Secondary outcomes:
measure: Time to GIR Responses
timeFrame: From the day after surgery (Day 1) until hospital discharge or Day 10 (whichever is earlier)
measure: Time to Discharge
timeFrame: From surgery to hospital discharge
measure: GIR Outcome Related to Length of Hospitalization (Mean)
timeFrame: From surgery to hospital discharge
measure: GIR Outcome Related to Length of Hospitalization (Median)
timeFrame: From surgery to hospital discharge
measure: Percentage of GIR Responders
timeFrame: From the day after surgery (Day 1) until hospital discharge or Day 10 (whichever is earlier)
measure: POI-related Morbidity
timeFrame: From the day after surgery to discharge follow-up visit (30 days (+ 15 days) after hospital discharge)
measure: Number of Participants With Adverse Events
timeFrame: From baseline to discharge follow-up visit (30 days (+ 15 days) after hospital discharge)
Other outcomes:
measure: Subject-Reported Occurrence of Nausea
timeFrame: From the day after surgery (Day 1) until hospital discharge or Day 10 (whichever is earlier)
measure: Subject-Reported Bothersomeness of Nausea
timeFrame: From the day after surgery (Day 1) until hospital discharge or Day 10 (whichever is earlier)
measure: Subject-Reported Occurrence of Abdominal Bloating
timeFrame: From the day after surgery (Day 1) until hospital discharge or Day 10 (whichever is earlier)
measure: Subject-Reported Bothersomeness of Abdominal Bloating
timeFrame: From the day after surgery (Day 1) until hospital discharge or Day 10 (whichever is earlier)
Locations:
city: Florence
country: United States
facility: Florence Site
state: Alabama
city: Gilbert
country: United States
facility: Gilbert Site
state: Arizona
city: Little Rock
country: United States
facility: Little Rock Site
state: Arkansas
city: Duarte
country: United States
facility: Duarte Site
state: California
city: Los Angeles
country: United States
facility: Los Angeles Site #1
state: California
city: Los Angeles
country: United States
facility: Los Angeles Site #2
state: California
city: Palo Alto
country: United States
facility: Palo Alto Site
state: California
city: Sacramento
country: United States
facility: Sacramento Site
state: California
city: Danbury
country: United States
facility: Danbury Site
state: Connecticut
city: Clearwater
country: United States
facility: Clearwater Site
state: Florida
city: Orlando
country: United States
facility: Orlando Site
state: Florida
city: Tampa
country: United States
facility: Tampa Site
state: Florida
city: Weston
country: United States
facility: Weston Site
state: Florida
city: Chicago
country: United States
facility: Chicago Site #2
state: Illinois
city: Chicago
country: United States
facility: Chicago Site #1
state: Illinois
city: Urbana
country: United States
facility: Urbana Site
state: Illinois
city: Lexington
country: United States
facility: Lexington Site
state: Kentucky
city: Metairie
country: United States
facility: Metairie Site
state: Louisiana
city: Boston
country: United States
facility: Boston Site #1
state: Massachusetts
city: Detroit
country: United States
facility: Detroit Site
state: Michigan
city: Saint Louis
country: United States
facility: St. Louis Site
state: Missouri
city: Newark
country: United States
facility: Newark Site
state: New Jersey
city: Mineola
country: United States
facility: Mineola Site
state: New York
city: New York
country: United States
facility: New York Site
state: New York
city: Stony Brook
country: United States
facility: Stony Brook Site
state: New York
city: Cleveland
country: United States
facility: Cleveland Site #2
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Site #1
state: Ohio
city: Philadelphia
country: United States
facility: Philadelphia Site #2
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Pittsburgh Site
state: Pennsylvania
city: Charleston
country: United States
facility: Charleston Site
state: South Carolina
city: Memphis
country: United States
facility: Memphis Site
state: Tennessee
city: Dallas
country: United States
facility: Dallas Site
state: Texas
city: Fort Worth
country: United States
facility: Fort Worth Site
state: Texas
city: Salt Lake City
country: United States
facility: Salt Lake City Site
state: Utah
city: Roanoke
country: United States
facility: Roanoke Site
state: Virginia
city: Milwaukee
country: United States
facility: Milwaukee Site
state: Wisconsin
Study officials:
References: