A Tolerability and Efficacy Study of TU-100 For The Treatment of Postoperative Ileus

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tsumura USA
ClinicalTrials.gov Identifier:
NCT00266461
First received: December 14, 2005
Last updated: July 11, 2013
Last verified: June 2012
  Purpose

Postoperative ileus (POI), a transient impairment of gastrointestinal (GI) motility, commonly occurs in patients who have undergone abdominal surgery and contributes to postoperative morbidity, including delayed enteral nutrition, increased patient discomfort, and prolonged hospitalization. POI appears to be have many causes, with activation of inhibitory reflexes, inflammatory responses, and the effects of anesthesia and analgesics all playing roles. However, there is no approved pharmacological therapy for the treatment and prevention of POI.

Daikenchuto (TU-100) is an herbal formulation consisting of Asian ginseng, Zanthoxylum fruit (Sichuan pepper), ginger, and malt sugar, which was originally described in Jin kui yao lue, the classical medical textbook written in ancient China in the third century by Zhang Zhong Jing. Since it was introduced to Japan, Daikenchuto has been used in the treatment of abdominal pain and a feeling of coldness in the abdomen.

TSUMURA Daikenchuto Extract Granules, Product Code TU-100, is a modern herbal product manufactured in the dosage form of granules by Tsumura & Co. The current Tsumura product, TU-100, was approved for manufacture as a prescription drug in 1986 by the Japanese Ministry of Health and Welfare and has been sold commercially as a prescription Kampo (a generic term for the system of traditional medicine that was developed in Japan after being introduced from China in the fourth century) drug in Japan for many years. The drug product proposed for use in the clinical studies is identical to the drug currently sold in Japan. In addition, all three botanical components and maltose syrup powder are considered as food substances and are currently part of the United States food supply.

The purpose of this study evaluate the tolerability, efficacy and safety of TU-100 for the treatment of postoperative ileus (POI) in patients undergoing laparotomy for large bowel resection


Condition Intervention Phase
Postoperative Ileus
Drug: Daikenchuto Extract Granules (TU-100)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Controlled, Open-Label Tolerability And Efficacy Study Of TU-100 For The Treatment Of Postoperative Ileus In Patients Undergoing Laparotomy For Large Bowel Resection

Further study details as provided by Tsumura USA:

Primary Outcome Measures:
  • Evaluate the tolerability of TU-100 for the treatment of postoperative ileus (POI) in patients undergoing laparotomy for large bowel resection based on the incidence of adverse events (AEs). [ Time Frame: Up to 10 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To evaluate the safety of TU-100 in the treatment of POI based on an assessment of objective and subjective symptoms and clinical laboratory data [ Time Frame: Up to 10 days ] [ Designated as safety issue: Yes ]
  • To evaluate the efficacy of TU-100 in the treatment of POI based on the length of time from the end of surgery to gastrointestinal(GI) function recovery and time to discharge order, and [ Time Frame: Up to 10 days ] [ Designated as safety issue: Yes ]
  • To determine the acceptability of TU-100 to American patients based on the number of discontinuations due to noncompliance and an assessment of taste. [ Time Frame: Up to 10 days ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: December 2005
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TU-100 7.5g/day
Subjects will be randomized to TU-100 7.5g, 15g, or no active treatment group. Subjects will take a daily dose divided into 3 times a day.
Drug: Daikenchuto Extract Granules (TU-100)
Experimental: TU-100 15g/day
Subjects will be randomized to TU-100 7.5g, 15g, or no active treatment group. Subjects will take a daily dose divided into 3 times a day.
Drug: Daikenchuto Extract Granules (TU-100)
No Intervention: Water
Subjects will be randomized to TU-100 7.5g, 15g, or no active treatment group. Subjects will take a daily dose divided into 3 times a day.

Detailed Description:

This is a randomized, controlled, open-label study designed to evaluate the tolerability and efficacy of TU-100 for the treatment of POI in patients undergoing laparotomy for large bowel resection. It will be conducted at multiple centers in the United States. A total of 24 patients will be enrolled in the study. Patient participation in the study will last for up to 32 days (from Screening to postoperative day 10 [POD 10] or until the time when a discharge order is written for the patient, whichever comes first), with follow-up safety assessments to occur 7 and 14 days after the last dose of study medication.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

In order to participate in this study, a patient must meet all of the following criteria:

  1. Is at least 18 years of age;
  2. Is male or female. Female patients cannot be pregnant or lactating and must be surgically sterile, postmenopausal (no menses for the previous 12 months), or practicing an effective method of birth control as determined by the investigator (eg, oral contraceptives, double barrier methods, hormonal injectable or implantable contraceptives, tubal ligation, or partner with vasectomy);
  3. Has been diagnosed with sigmoid carcinoma; ascending, transverse, or descending colon carcinoma; colonic polyps; carcinoid tumors; lymphoma localized to the abdomen; ischemic bowel; toxic megacolon with no perforation; any tumor of the bowel determined to require removal; or diverticulitis;
  4. Requires laparotomy for large bowel resection. Note: patients who are shifted to laparotomy during laparoscopic surgery are acceptable;
  5. Is hospitalized for surgery and recovery;
  6. Has a pre-operative Karnofsky performance status of 80% to 100%; and
  7. Provides written informed consent prior to participation in the study after full explanations of the study purpose and procedures.

Exclusion Criteria:

In order to participate in this study, a patient must not meet any of the following criteria:

  1. Has been diagnosed with Crohn's disease, ulcerative colitis, or irritable bowel syndrome. Note: patients with inactive ulcerative colitis who are in stable clinical remission and/or on maintenance therapy to prevent relapse are acceptable;
  2. Is a pregnant or lactating female;
  3. Requires a colostomy or any other ostomy device placement;
  4. Requires emergency surgery or has surgery in the presence of an ongoing infection, including bowel obstruction and perforated bowel;
  5. Has colorectal cancer with a Dukes Classification score of D;
  6. Has diabetic neuropathy;
  7. Has a history of gastroparesis;
  8. Has a compromised immune system, either from treatment with corticosteroids or other immunosuppressive agents within 2 weeks of surgery or from immunosuppressive diseases (eg, human immunodeficiency virus); Note: patients on chronic treatment (for at least 3 months) with corticosteroids of up to 10 mg daily of prednisone or equivalent are acceptable if dosing has been stable for at least 2 weeks;
  9. Has any other serious condition that might adversely affect their safety or ability to participate in this study, such as liver disorders (including alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST] levels greater than 2.5 times the upper limit of normal [ULN]), kidney disorders, heart failure, blood disorders, or metabolic disorders;
  10. Has a history of any allergic reactions to ginseng, ginger, Zanthoxylum fruit (Sichuan pepper), or maltose;
  11. Has a history of narcotic drug abuse (especially heroin or opium) or chronic narcotic use for pain management within 2 weeks of surgery;
  12. Requires anticancer radiation or chemotherapy within 2 weeks of surgery;
  13. Has a history of laparotomy or laparoscopy other than simple laparoscopic procedures such as cholecystectomy, gynecological procedures, or inguinal hernia repair. Note: a history of laparoscopic fundoplication is exclusive, while a history of appendectomy or hysterectomy is acceptable; patients who have had laparotomy procedures in the past with no history of subsequent small bowel or large bowel obstruction are acceptable;
  14. Has a history of any type of ileus;
  15. Has a history of receiving abdominal radiation therapy in addition to subsequent small bowel or large bowel obstruction. Note: a history of radiation therapy with no small bowel or large bowel obstruction is acceptable; a history of pelvic radiation therapy is also acceptable;
  16. Is unwilling or unable to comply with the procedures described in this protocol or is otherwise unacceptable for enrollment in the opinion of the investigator; and
  17. Has participated in any other investigational product or device trial within 30 days prior to enrolling in this study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00266461

Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Tsumura USA
Investigators
Study Director: Shunji Mochida, PhD Tsumura USA Inc.
  More Information

No publications provided

Responsible Party: Tsumura USA
ClinicalTrials.gov Identifier: NCT00266461     History of Changes
Other Study ID Numbers: TU100P2T1
Study First Received: December 14, 2005
Last Updated: July 11, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Tsumura USA:
Postoperative Ileus

Additional relevant MeSH terms:
Ileus
Intestinal Obstruction
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on October 19, 2014