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Efficacy and Safety of Rifaximin for Patients With Chronic Intestinal Pseudo-obstruction: a Phase 2 Trial

Phase 2
Conditions
Chronic Intestinal Pseudo-obstruction
Interventions
Drug: Placebo oral tablet
Registration Number
NCT04118699
Lead Sponsor
Yokohama City University
Brief Summary

The objective of the study is to investigate efficacy and safety of rifaximin (L-105) in patients with chronic idiopathic intestinal pseudo-obstruction(CIIPO) or patients with chronic intestinal pseudo-obstruction (CIPO), secondary to systemic scleroderma

Detailed Description

This is a placebo-controlled, randomized, double-blind, parallel group, comparative study, when patients with chronic idiopathic intestinal pseudo-obstruction(CIIPO) or patients with chronic intestinal pseudo-obstruction (CIPO), secondary to the onset of systemic scleroderma, are administered rifaximin at 400 mg 3 times daily for 4 weeks. In addition, the time course of symptoms of the patients are to be confirmed for 8 weeks after the end of administration.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
12
Inclusion Criteria
  • Outpatients aged ≥20 and <75 on the day of informed consent (IC)
  • Patients with CIIPO (designated intractable disease 99) at enrollment, satisfying all the criteria specified in (1) to (7) of the CIIPO Diagnostic Criteria issued in 2014 by the MHLW Research Group, or patients with CIPO, secondary to systemic scleroderma, satisfying all the same criteria specified in (1) to (6)
  • Patients' levels of abdominal bloating symptoms, 4 scales of GSS, should be score 2 or 3 at the time of IC acquisition and enrollment.
Exclusion Criteria
  • Patients with malignant diseases (excluding those whose symptoms are stable and who do not require aggressive treatments such as chemotherapy and/or surgical therapy)
  • Patients with psychiatric diseases (excluding those whose symptoms are stable, and the investigator or coinvestigator concludes that efficacy of the patient can be assessed without any issue)
  • Patients with severe diabetes within 5 weeks before enrollment (HbA1c >10%)
  • Patients who have already had gastrostomy (including percutaneousendoscopic gastro -jejunostomy, PEG-J), enterostomy, or colostomy
  • Patients who underwent intestinal decompression therapy not associated with surgical procedures (trans-nasal ileus tube) within 4weeks before enrollment
  • Patients who used antimicrobials, antiparasitics or antifungals (excluding topical use) within 4 weeks before enrollment
  • Patients who have changed the doses of the following concomitantly administered drugs within 4 weeks before enrollment: mosapride, daikenchuto, metoclopramide, acotiamide
  • Patients with severe hepatic disorders within 5 weeks before enrollment (who meet either one of the following criteria: AST≥ 5 x the upper limit of the common reference value specified in the Japanese Committee for Clinical Laboratory Standards (JCCLS), ALT≥ 5 x the upper limit of the common reference value specified in JCCLS, total bilirubin ≥ 3 x the upper limit of the common reference value specified in JCCLS, decompensated hematic cirrhosis, or jaundice)
  • Patients who are pregnant, breastfeeding, possibly pregnant, or those who wish to become pregnant
  • Patients with a previous history of hypersensitivity to any investigational product ingredients
  • Patients with active tuberculosis
  • Patients who participated in other clinical trial (including a trial with an investigational product) within 12 weeks before this enrollment and who received an intervention with a test drug
  • Other patients whose participation in the trial is concluded to be inappropriate by the investigator or coinvestigator

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
RifaximinRifaximin oral tabletTwo tablets of the investigational product per dosing (400 mg of rifaximin) are orally administered 3 times daily for 4 weeks.
PlaceboPlacebo oral tabletTwo tablets of the placebo are orally administered 3 times daily for 4 weeks.
Primary Outcome Measures
NameTimeMethod
Improvement ratio (%) in abdominal bloating score in Global Symptomatic Score (GSS)at the end of administration (4 weeks)

Abdominal bloating score in Global Symptomatic Score (GSS) is used. GSS is a 4-point Likert scale ranging from 0 (no symptom) to 3 (severe, incapacitating with inability to perform normal activities), with lower scores reflecting better symptoms. Score 0 or 1 is defined as improvement.

Improvement ratio (%) in Gastrointestinal (GI) symptoms scoreat the end of administration (4 weeks)

Gastrointestinal score (GI score) is a 5-point Likert scale (0; greatly improved, 1; improved, 2; no change, 3; worsened, 4; severely worsened), with lower scores reflecting more improved symptoms. Score 0 or 1 is defined as improvement.

Secondary Outcome Measures
NameTimeMethod
Changes from baseline of cholinesteraseBefore, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration

Cholinesterase is calculated for nutritional assessment

Changes from baseline of prealbumin (transthyretin)Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration

Prealbumin (transthyretin) is calculated for nutritional assessment

Changes of Short Form (SF)-8 health survey scoreBefore, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration

SF-8(short form-8), a self-reporting health survey ranging from 8 to maximum of 42, with lower scores reflecting better conditions, is used.

Changes of the improvement ratio (%) in abdominal bloating scoreBefore, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration

Abdominal bloating score in Global Symptomatic Score (GSS) is used. GSS is a 4-point likert scale ranging from 0 (no symptom) to 3 (severe, incapacitating with inability to perform normal activities), with lower scores reflecting better symptoms. Score 0 or 1 is defined as improvement.

Changes of abdominal bloating scoreBefore, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration

Abdominal bloating score in Global Symptomatic Score (GSS) is used. GSS is a 4-point likert scale ranging from 0 (no symptom) to 3 (severe, incapacitating with inability to perform normal activities), with lower scores reflecting better symptoms.

Changes of the improvement ratio (%) in gastrointestinal symptoms scoreBefore, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration

Gastrointestinal score (GI score), a 5-point likert scale (0; greatly improved, 1; improved, 2; no change, 3; worsened, 4; severely worsened), with lower scores reflecting more improved symptoms, is used. Score 0 or 1 is defined as improvement.

Changes of the "good" ratio (%) in gastrointestinal symptoms scoreBefore, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration

Gastrointestinal score (GI score), 5-point likert scale (0; very good, 1; good, 2; average, 3; bad, 4; extremely bad), with lower scores reflecting better conditions, is used. Score 0 or 1 is defined as ''good''.

Changes of each score in Global Symptomatic Score other than abdominal bloating scoreBefore, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration

Global Symptomatic Score (GSS), a 4-point likert scale ranging from 0 (no symptom) to 3 (severe), of the following symptoms are assessed; (a. diarrhea, b. epigastric pain/ discomfort, c. pain in the lower quadrant/discomfort, d. tenderness, e. nausea, f. vomiting).

Changes of total scores in Global Symptomatic ScoreBefore, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration

Sum of Global Symptomatic Score (GSS) of the following 7 symptoms, 0 to maximum of 21, are assessed; (a. diarrhea, b. epigastric pain/discomfort, c. abdominal distention, d. pain in the lower quadrant/discomfort, e. tenderness, f. nausea, g. vomiting).

Changes of the improvement ratio (%) in General health condition (symptoms) scoreBefore, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration

General health condition (symptoms) score, a 5-point likert scale (0; greatly improved, 1; improved, 2; no change, 3; worsened, 4; severely worsened), with lower scores reflecting more improved symptoms, is used. Score 0 or 1 is defined as improvement.

Changes of the "good" ratio (%) in General health condition (symptoms) scoreBefore, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration

General health condition (symptoms) score, 5-point scale (0; very good, 1; good, 2; average, 3; bad, 4; extremely bad), with lower scores reflecting better conditions, is used. Score 0 or 1 is defined as ''good''.

Patient satisfaction scoreAt the end of the administration (4 weeks)

% of the "satisfaction" ratio in patient satisfaction score

Small intestinal volume measured by abdominal CT scanBefore, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration

Changes of small intestinal volume measured by abdominal CT scan

Changes from baseline of serum albumin levelBefore, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration

Serum albumin level is calculated for nutritional assessment

Changes from baseline of folic acidBefore, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration

Folic acid is calculated for nutritional assessment

Changes from baseline of vitamin B12 (cobalamin)Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration

Vitamin B12 (cobalamin) is calculated for nutritional assessment

Changes from baseline of serum ironBefore, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration

Serum iron is calculated for nutritional assessment

Trial Locations

Locations (1)

Yokohama city university

🇯🇵

Yokohama, Kanagawa, Japan

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