Daikenchuto for Intestinal Dysmotility and Prevention of Postoperative Paralytic Ielus After Pancreaticoduodenectomy

Study Overview
=================
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).

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

Conditions
-----------------
Paralytic Ileus

Intervention / Treatment
-----------------
* Drug: Oral/enteral TJ-100 solution
* Drug: Oral/enteral placebo solution


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Oral/enteral TJ-100 solution<br>Oral/enteral TJ-100 solution | Drug: Oral/enteral TJ-100 solution<br>* 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.<br>* Other names: A;|
| Placebo Comparator: Oral/enteral placebo solution<br>Oral/enteral placebo solution | Drug: Oral/enteral placebo solution<br>* 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.<br>* Other names: B;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 72 hours | 
| 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. | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 7 days | 
| 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. | 3 days | 
| The change ratio of abdominal circumference. | The change ratio of abdominal circumference on postoperative day 3 and operative day just after surgery | 3 days | 
| The incidence of postoperative complication. | The incidence of postoperative complication based on Dindo's classification. | 14 days | 
| 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. | 30 days | 
| 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. | 30 days | 
| 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. | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
daikenchuto, postoperative ileus, pancreaticoduodenectomy