Daikenchuto for Intestinal Dysmotility and Prevention of Postoperative Paralytic Ielus After Pancreaticoduodenectomy (JAPAN-PD)
Primary Purpose
Paralytic Ileus
Status
Unknown status
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
Oral/enteral TJ-100 solution
Oral/enteral placebo solution
Sponsored by
About this trial
This is an interventional prevention trial for Paralytic Ileus focused on measuring daikenchuto, postoperative ileus, pancreaticoduodenectomy
Eligibility Criteria
Inclusion Criteria:
- Patients with periampullary tumors (extrahepatic bile duct tumor, tumors of ampulla of Vater and duodenal tumor) and pancreatic tumors (pancreatic cancer, intraductal papillary mucinous neoplasm of the pancreas, pancreatic endocrine tumor and pancreatic neuroendocrine tumor) of the head of the pancreas who are scheduled to undergo PD.
- Age of at least 20 years old at the time of registration.
- All patients provided written informed consent before initiation of study-related procedures.
Exclusion Criteria:
- Clinically problematic cardiac disease.
- Liver cirrhosis or active hepatitis.
- Severe pulmonary disease (interstitial pneumonia, pulmonary fibrosis, pulmonary emphysema etc.).
- Chronic renal failure requiring hemodialysis.
- Other malignant disease that can influence the adverse effect.
- Patients with tumors requiring resection of colon.
- Patients who are expected to have severe intra-abdominal adhesion due to past surgical history or past peritonitis history.
- Patients who had used gastrointestinal prokinetic medication, antipsychotic medication or antidepressants.
- Patients who had used Japanese herbal (Kampo) medicines within 4 weeks before registration.
- Pregnant or lactating women.
- Any other medical condition that makes the patient unsuitable for inclusion in the study according to the opinion of the investigator.
Sites / Locations
- Nagoya University
- Osaka University
- Hiroshima University
- Shizuoka Cancer Center Hospital
- Wakayama Medical University
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Oral/enteral TJ-100 solution
Oral/enteral placebo solution
Arm Description
Oral/enteral TJ-100 solution
Oral/enteral placebo solution
Outcomes
Primary Outcome Measures
Incidence of postoperative paralytic ileus (including the duration of paralysis)
Delayed passage of first flatus for 72 hours (3.0 days) after surgery, or a postoperative condition that requires an intervention for the ileus. Every 12 hours is counted as 0.5 postoperative day and every 24 hours as 1.0 postoperative day.
The duration until the first flatus after surgery.
The first passages of flatus will be confirmed by patients themselves and they will inform it to the medical staffs.
Secondary Outcome Measures
QOL assessment by the Gastrointestinal Symptom Rating Scale (GSRS) Score (Japanese Version)
QOL assessment by the Gastrointestinal Symptom Rating Scale (GSRS) Score (Japanese Version) on postoperative day 7.
Abdominal pain and abdominal distention scores on the Visual Analogue Scale.
Abdominal pain and abdominal distention scores on the Visual Analogue Scale on postoperative day 3.
The change ratio of abdominal circumference.
The change ratio of abdominal circumference on postoperative day 3 and operative day just after surgery
The incidence of postoperative complication.
The incidence of postoperative complication based on Dindo's classification.
The length of postoperative hospital day.
Patients were discharged only when they fulfilled the criteria as follows: a return to preoperative activities of daily living, no deep-site infections, normal laboratory data, no drains, and the possibility for oral nutrition above the basal metabolism.
The incidence of surgical site infection.
Intra-abdominal abscess was defined as intra-abdominal fluid collection with positive cultures identified by ultrasonography or computed tomography associated with persistent fever and elevations of white blood cell counts.
The long term incidence of postoperative ileus after surgery.
The follow-up investigation of the long term incidence of postoperative ileus is scheduled in two years after surgery.
Full Information
NCT ID
NCT01607307
First Posted
May 16, 2012
Last Updated
December 17, 2013
Sponsor
Wakayama Medical University
Collaborators
Epidemiological and Clinical Research Information Network
1. Study Identification
Unique Protocol Identification Number
NCT01607307
Brief Title
Daikenchuto for Intestinal Dysmotility and Prevention of Postoperative Paralytic Ielus After Pancreaticoduodenectomy
Acronym
JAPAN-PD
Official Title
Effect of Daikenchuto (TJ-100) on Intestinal Dysmotility and For the Prevention of Postoperative Paralytic Ileus in Patients Undergoing Pancreaticoduodenectomy: A Multicenter, Randomized, Placebo-Controlled Phase II Trial
Study Type
Interventional
2. Study Status
Record Verification Date
August 2012
Overall Recruitment Status
Unknown status
Study Start Date
August 2012 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
August 2016 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Wakayama Medical University
Collaborators
Epidemiological and Clinical Research Information Network
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
A multicenter randomized-controlled trial of daikenchuto (TJ-100), a traditional Japanese herbal medicine (Kampo), to investigate its effect on intestinal dysmotility and for the prevention of postoperative paralytic ileus.
Detailed Description
Daikenchuto (TJ-100), a traditional Japanese herbal medicine, is used for prevention and treatment of postoperative ileus. TJ-100 extract powder (Tsumura & Co., Tokyo, Japan) is manufactured as an aqueous extract containing 2.2 % Japanese pepper, 5.6 % processed ginger, 3.3 % ginseng, and 88.9 % maltose syrup powder. A recent randomized, parallel-group, double-blind, placebo-controlled, dose-response trial demonstrated that TJ-100 accelerates colonic transit time, particularly in the ascending colon. Given its potential actions in the intestinal tract, it seems reasonable to postulate that TJ-100 may play a role in improving and preventing bowel dysmotility. This study was designed to investigate the effect of TJ-100 on intestinal dysmotility and for the prevention of postoperative paralytic ileus in patients undergoing pancreaticoduodenectomy.
The primary endpoint is the incidence of postoperative paralytic ileus. Secondary endpoints are QOL assessment by the Gastrointestinal Symptom Rating Scale (GSRS) Score (Japanese Version) and visual analogue scale, the change in ratio of abdominal circumference, the incidence of postoperative complications, the length of hospital day, and the incidence of surgical site infection. Two hundred patients are required for the study (100 patients per group).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Paralytic Ileus
Keywords
daikenchuto, postoperative ileus, pancreaticoduodenectomy
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
220 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Oral/enteral TJ-100 solution
Arm Type
Active Comparator
Arm Description
Oral/enteral TJ-100 solution
Arm Title
Oral/enteral placebo solution
Arm Type
Placebo Comparator
Arm Description
Oral/enteral placebo solution
Intervention Type
Drug
Intervention Name(s)
Oral/enteral TJ-100 solution
Other Intervention Name(s)
A
Intervention Description
Oral TJ-100 solution (5 g tid, 15 g/day) given immediately before meals or every 8 h from preoperative day 3 to postoperative day 7 for 10 consecutive days. A diluent TJ-100 solution given immediately after surgery and on postoperative day 1 via Argyle enteral feeding tube (10 Fr), which terminates in the jejunum to prevent aspiration pneumonia.
Intervention Type
Drug
Intervention Name(s)
Oral/enteral placebo solution
Other Intervention Name(s)
B
Intervention Description
Oral placebo solution (5 g tid, 15 g/day) given immediately before meals or every 8 h from preoperative day 3 to postoperative day 7 for 10 consecutive days. A diluent placebo solution given immediately after surgery and on postoperative day 1 via Argyle enteral feeding tube (10 Fr), which terminates in the jejunum to prevent aspiration pneumonia.
Primary Outcome Measure Information:
Title
Incidence of postoperative paralytic ileus (including the duration of paralysis)
Description
Delayed passage of first flatus for 72 hours (3.0 days) after surgery, or a postoperative condition that requires an intervention for the ileus. Every 12 hours is counted as 0.5 postoperative day and every 24 hours as 1.0 postoperative day.
Time Frame
72 hours
Title
The duration until the first flatus after surgery.
Description
The first passages of flatus will be confirmed by patients themselves and they will inform it to the medical staffs.
Time Frame
14 days
Secondary Outcome Measure Information:
Title
QOL assessment by the Gastrointestinal Symptom Rating Scale (GSRS) Score (Japanese Version)
Description
QOL assessment by the Gastrointestinal Symptom Rating Scale (GSRS) Score (Japanese Version) on postoperative day 7.
Time Frame
7 days
Title
Abdominal pain and abdominal distention scores on the Visual Analogue Scale.
Description
Abdominal pain and abdominal distention scores on the Visual Analogue Scale on postoperative day 3.
Time Frame
3 days
Title
The change ratio of abdominal circumference.
Description
The change ratio of abdominal circumference on postoperative day 3 and operative day just after surgery
Time Frame
3 days
Title
The incidence of postoperative complication.
Description
The incidence of postoperative complication based on Dindo's classification.
Time Frame
14 days
Title
The length of postoperative hospital day.
Description
Patients were discharged only when they fulfilled the criteria as follows: a return to preoperative activities of daily living, no deep-site infections, normal laboratory data, no drains, and the possibility for oral nutrition above the basal metabolism.
Time Frame
30 days
Title
The incidence of surgical site infection.
Description
Intra-abdominal abscess was defined as intra-abdominal fluid collection with positive cultures identified by ultrasonography or computed tomography associated with persistent fever and elevations of white blood cell counts.
Time Frame
30 days
Title
The long term incidence of postoperative ileus after surgery.
Description
The follow-up investigation of the long term incidence of postoperative ileus is scheduled in two years after surgery.
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with periampullary tumors (extrahepatic bile duct tumor, tumors of ampulla of Vater and duodenal tumor) and pancreatic tumors (pancreatic cancer, intraductal papillary mucinous neoplasm of the pancreas, pancreatic endocrine tumor and pancreatic neuroendocrine tumor) of the head of the pancreas who are scheduled to undergo PD.
Age of at least 20 years old at the time of registration.
All patients provided written informed consent before initiation of study-related procedures.
Exclusion Criteria:
Clinically problematic cardiac disease.
Liver cirrhosis or active hepatitis.
Severe pulmonary disease (interstitial pneumonia, pulmonary fibrosis, pulmonary emphysema etc.).
Chronic renal failure requiring hemodialysis.
Other malignant disease that can influence the adverse effect.
Patients with tumors requiring resection of colon.
Patients who are expected to have severe intra-abdominal adhesion due to past surgical history or past peritonitis history.
Patients who had used gastrointestinal prokinetic medication, antipsychotic medication or antidepressants.
Patients who had used Japanese herbal (Kampo) medicines within 4 weeks before registration.
Pregnant or lactating women.
Any other medical condition that makes the patient unsuitable for inclusion in the study according to the opinion of the investigator.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hiroki Yamaue, M.D., Ph.D.
Organizational Affiliation
Second Department of Surgery, Wakayama Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Nagoya University
City
Nagoya
State/Province
Aichi
Country
Japan
Facility Name
Osaka University
City
Suita
State/Province
Osaka
Country
Japan
Facility Name
Hiroshima University
City
Hiroshima
Country
Japan
Facility Name
Shizuoka Cancer Center Hospital
City
Shizuoka
Country
Japan
Facility Name
Wakayama Medical University
City
Wakayama
ZIP/Postal Code
641-8510
Country
Japan
12. IPD Sharing Statement
Citations:
PubMed Identifier
30333892
Citation
Maeda H, Okada KI, Fujii T, Oba MS, Kawai M, Hirono S, Kodera Y, Sho M, Akahori T, Shimizu Y, Ambo Y, Kondo N, Murakami Y, Ohuchida J, Eguchi H, Nagano H, Sakamoto J, Yamaue H. Transition of serum cytokines following pancreaticoduodenectomy: A subsidiary study of JAPAN-PD. Oncol Lett. 2018 Nov;16(5):6847-6853. doi: 10.3892/ol.2018.9422. Epub 2018 Sep 7.
Results Reference
derived
PubMed Identifier
26747224
Citation
Okada K, Kawai M, Hirono S, Fujii T, Kodera Y, Sho M, Nakajima Y, Satoi S, Kwon AH, Shimizu Y, Ambo Y, Kondo N, Murakami Y, Ohuchida J, Eguchi H, Nagano H, Oba MS, Morita S, Sakamoto J, Yamaue H; JAPAN-PD Investigators. Evaluation of the efficacy of daikenchuto (TJ -100) for the prevention of paralytic ileus after pancreaticoduodenectomy: A multicenter, double-blind, randomized, placebo-controlled trial. Surgery. 2016 May;159(5):1333-41. doi: 10.1016/j.surg.2015.11.019. Epub 2015 Dec 31.
Results Reference
derived
Learn more about this trial
Daikenchuto for Intestinal Dysmotility and Prevention of Postoperative Paralytic Ielus After Pancreaticoduodenectomy
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