A Study of TAK-954 to Treat Gastrointestinal Dysfunction in Adults After Surgery
- Conditions
- Postoperative Gastrointestinal Dysfunction
- Interventions
- Drug: TAK-954 PlaceboDrug: TAK-954
- Registration Number
- NCT03827655
- Lead Sponsor
- Takeda
- Brief Summary
The main aim of this study is to check for side effects from TAK-954 and whether it speeds up the recovery of gastrointestinal function after small-bowel or large-bowel resection surgery.
Participants will be treated with TAK-954 before surgery and up to 10 days after surgery.
- Detailed Description
The drug being tested in this study is called TAK-954. In this study TAK-954 is being administered presurgery to evaluate if it can enhance the recovery of GI function postsurgery in participants undergoing open or laparoscopic-assisted partial small- or large-bowel resection. In addition, some participants will also receive TAK-954 postoperatively to evaluate if there is an additional benefit when this drug is administered both pre and post-surgery.
The study will enroll approximately 180 participants. Participants will be equally randomized into one of the three remaining parallel treatment arms- which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need).
All participants will be given intravenous infusion preoperation and daily postoperation until return of upper and lower GI function or for up to 10 days.
This multi-center trial will be conducted in the United States and Germany. The overall time to participate in this study is up to 100 days. Participants will be treated with the study drug for up to 10 days after surgery or until return of GI function post-surgery (whichever occurs first).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 209
- Participant is scheduled to undergo a laparoscopic-assisted or open partial small- or large-bowel resection.
- Participant's American Society of Anesthesiologists (ASA) physical status classification is ASA 1 to 3.
- Has significant mechanical bowel obstruction that is not expected to resolve after the surgery, short bowel syndrome, pre-existing clinically significant GI motility disorder (example, gastroparesis, scleroderma, chronic intestinal pseudo-obstruction), uncontrolled diabetes (glycosylated hemoglobin [HbA1c] greater than [>] 10 percent [%]), has an active gastric pacemaker, or requires parenteral nutrition.
- Had previous major abdominal surgery (example, gastrectomy, gastric bypass, gastric sleeve, lap banding, Whipple, pancreatic resection, total/subtotal colectomy, hemicolectomy, extensive bowel resection).
- Had a history of radiation therapy to the abdomen or pelvis.
- Scheduled to undergo any of the following surgeries: low anterior resection, total or subtotal colectomy, colostomy, ileostomy or reversal of stoma, or has a diagnosis that requires rectal resection (eg, tumors in the anorectum) and will likely require lower anterior resection surgery. Participants with planned surgery for which there is no anticipated significant rectal resection and is, therefore, likely to preserve anorectal function and continence postsurgery, will likely be eligible for inclusion in the study if they meet all the study inclusion/exclusion criteria (eg, participants with lesions not involving the rectum [sigmoid colon and above]).
- Has pre-existing hepatic disease that meets Child-Pugh Class B (moderate; total score 7 to 9 points) or C (severe; total score 10 to 15 points).
- Has received alvimopan, erythromycin, prucalopride, metoclopramide, domperidone, cisapride, mosapride, renzapride, or azithromycin in the 24 hours prior to starting study drug.
- Participant has known COVID-19 infection, or suspected COVID-19 infection.
- Scheduled for abdominal surgery that is classified as emergency.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description TAK-954 0.1 mg/100 mL + Placebo TAK-954 TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function. TAK-954 0.5 mg/100 mL + Placebo TAK-954 Placebo TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function. TAK-954 0.5 mg/100 mL TAK-954 TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days. TAK-954 0.1 mg/100 mL TAK-954 TAK-954 0.1 milligrams per 100 milliliters (mg/100 mL), 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days. Placebo TAK-954 Placebo TAK-954 placebo-matching, 60-minute infusion, intravenously (IV), once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days. TAK-954 0.1 mg/100 mL + Placebo TAK-954 Placebo TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function. TAK-954 0.5 mg/100 mL + Placebo TAK-954 TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.
- Primary Outcome Measures
Name Time Method Time From End of the Surgery to Resolution of Upper and Lower Gastrointestinal (GI) Function Postsurgery as Assessed by the Investigator Day 1 (surgery) up to Day 10 postsurgery The time from end of surgery to tolerance of solid food, without first occurrence of vomiting or clinically significant nausea for 1 calendar day after a solid meal (upper GI function) and first spontaneous bowel movement (lower GI function), whichever occurred later up to 10 days postsurgery was observed. Kaplan-Meier survival analysis method was used.
- Secondary Outcome Measures
Name Time Method Time From the End of Surgery to Discharge From Hospital Day 1 (surgery) up to Day 24 Kaplan-Meier survival analysis method was used.
Time From End of Surgery to First Spontaneous Bowel Movement as Assessed by the Investigator Day 1 (surgery) up to Day 10 postsurgery The time from end of surgery to first spontaneous bowel movement was defined as a stool not induced by the use of enemas or laxatives. Kaplan-Meier survival analysis method was used.
Percentage of Participants With Postoperative Gastrointestinal Dysfunction (POGD) >= 5 Days as Assessed by the Investigator Day 1 (surgery) up to Day 10 Participants unable to tolerate solid foods, take anything by mouth, or requiring insertion or reinsertion of nasogastric (NG) tube at or after 5 days post-surgery. Percentages are rounded off to whole number at the nearest single decimal. Stratified Miettinen and Nurminen approach was used for analysis.
Time From End of Surgery to Tolerance of Solid Food as Assessed by the Investigator Day 1 (surgery) up to Day 10 postsurgery The time from end of surgery to tolerance of solid food was defined as intake of solids without vomiting or clinically significant nausea for 1 calendar day after a solid meal. Kaplan-Meier survival analysis method was used.
Percentage of Participants Requiring Insertion of Nasogastric (NG) Tube Postsurgery Day 1 (surgery) up to Day 24 postsurgery (10 days of treatment period postsurgery plus 14-day observation period post last dose for recurrence of symptoms) Participants who required insertion of NG tube postsurgery for drainage and symptom relief in case of persistent nausea and vomiting postsurgery were observed. Percentages are rounded off to whole number at the nearest single decimal. Stratified Miettinen and Nurminen approach was used for analysis.
Time From the End of the Surgery (Time the Incision is Closed) Until Ready for Discharge as Assessed by the Investigator Day 1 (surgery) up to Day 24 The time from the end of surgery (time the incision is closed) until ready for discharge was defined as time from end of surgery until the participant presented effective intestinal transit (spontaneous bowel movement), tolerated solids without vomiting or clinically significant nausea for 1 calendar day after a solid meal, had satisfactory pain control with oral analgesics, and was medically stable/free of complications. Kaplan-Meier survival analysis method was used.
Time From the End of Surgery Until the Discharge Order is Written Day 1 (surgery) up to Day 24 Kaplan-Meier survival analysis method was used.
Time From End of Surgery to First Flatus Day 1 (surgery) up to first flatus (up to Day 10 postsurgery) Kaplan-Meier survival analysis method was used.
Observed Plasma Concentration of TAK-954 at the End of Infusion on Day 1 Day 1 (surgery): postinfusion
Trial Locations
- Locations (25)
Universitatsklinikum Freiburg
🇩🇪Freiburg, Baden-wuerttemberg, Germany
Sankt Josef-Hospital
🇩🇪Bochum, Nordrhein-westfalen, Germany
Universitatsklinikum Mannheim
🇩🇪Mannheim, Baden-wuerttemberg, Germany
Parkview Community Hospital Medical Center
🇺🇸Riverside, California, United States
Klinikum Rechts der Isar der Technischen Universitat Munchen
🇩🇪Munchen, Bayern, Germany
Keck School of Medicine
🇺🇸Los Angeles, California, United States
Penn State Health Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
University of South Alabama Medical Center
🇺🇸Mobile, Alabama, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
Cleveland Clinic Florida
🇺🇸Weston, Florida, United States
Universitaetsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Stony Brook University Hospital
🇺🇸Stony Brook, New York, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Fairview Hospital
🇺🇸Cleveland, Ohio, United States
Indiana University Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
HD Research Corp.
🇺🇸Houston, Texas, United States
North Star Medical
🇺🇸Houston, Texas, United States
University of California Irvine Medical Center
🇺🇸Orange, California, United States
University of Miami Leonard M. Miller School of Medicine
🇺🇸Miami, Florida, United States
Center for Colon & Rectal Surgery - Altamonte Springs
🇺🇸Orlando, Florida, United States
Ochsner Medical Center
🇺🇸New Orleans, Louisiana, United States
University of Massachusetts Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
The Ohio State University Wexner Medical Center
🇺🇸Columbus, Ohio, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Universitaetsklinikum Regensburg
🇩🇪Regensburg, Bavaria, Germany