Phase II clinical trial, conducted in different sites, with random assignation of treatment, where neither the patient or the medical doctor know the assigned treatment, drug or placebo, to evaluate the efficacy and safety of Rifaximin delayed release 400 mg tablet in the prevention of post-operative endoscopic Crohn’s disease recurrence
- Conditions
- Post-operative endoscopic Crohn’s disease recurrenceMedDRA version: 20.0 Level: LLT Classification code 10013099 Term: Disease Crohns System Organ Class: 100000004856Therapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- EUCTR2017-002258-36-BE
- Lead Sponsor
- ALFASIGMA S.P.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 180
?Patients of both sexes aged between 18 and 75 years old, inclusively.
?Patients with diagnosis of CD, who had undergone curative ileocolonic resection, with ileocolonic anastomosis and for whom a randomization within 45 days from surgical intervention is feasible.
?If the patients had an end or loop ileostomy within 1 year prior to randomization, they can be included, but stoma closure should occur within 45 days prior to randomization.
?Patients have had faecal stream restoration at least 14 days prior to randomization.
?Patients must have at least one of the following risk factors for the development of early/severe post-operative endoscopic recurrence of their CD:
1) qualifying surgery that was their second intestinal resection within 10 years
2) third or more intestinal resections,
3) surgery for a penetrating CD complication (e.g., abscess or fistula), or
4) smoking 10 or more cigarettes per day for the past year.
?Patients treated with glucocorticosteroids (systemic or topical) must discontinue treatment within 6 weeks after surgery.
?Patients are capable of and willing to adhere to the study protocol requirements.
?Patients have provided signed and dated written informed consent.
?Female patients must be:
?post-menopausal (at least 2 years without spontaneous menses), or
?surgically sterile (bilateral tubal ligation, or hysterectomy, or ablation of both ovaries),
?or have a negative urine pregnancy test result at screening and at randomization and agree to use an acceptable method of contraception throughout their participation in the study. Acceptable methods of contraception include: condom and spermicide; intrauterine device (IUD), diaphragm with spermicide; hormonal methods (oral contraceptives, patches, implants, injectable or ring) with a documented failure rate of less than 1% per year,
?or commit to absolute and continuous sexual abstinence
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 160
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20
?Presence of macroscopic evidence for CD proximally or distally to the site of resection (presence of frank erythema, oedema, aphthae, ulcers or wall thickening > 3 mm, or creeping fat) according to the surgeon or previous imaging
?Patients who had strictureplasties at index surgery
?Patients with an ileorectal anastomosis
?Patients with active perianal Crohn’s disease
?Patients treated with (treatment which was not discontinued at the time of surgery):
?Aminosalicylates
?Any biologicals (e.g., TNF-a inhibitor, natalizumab, or
similar drugs)
?Azathioprine, 6-mercaptopurine
?Methotrexate,
?Cyclosporine, tacrolimus, sirolimus, mycophenolate
mofetil, or similar drugs
?antibiotics specific for CD such as metronidazole or
ciprofloxacin
?Patients with active infectious, ischemic, or immunological diseases with GI involvement
?Patients with symptoms attributed to Short Bowel Syndrome (more than cm 100 in total of small bowel resected);
?Patients with sepsis or other post-operative complications necessitating use of antibiotics for more than 14 days after surgery.
?Patients with colorectal stenosis precluding ileocolonoscopy.
?Patients who had qualifying ileocolonic resection for dysplasia or cancer without ongoing inflammation
?Hepatic Impairment defined as severe (Child-Pugh C) hepatic impairment or patients with MELD (Model for End-Stage Liver Disease) score > 25.
?Patients with an alanine transaminase (ALT) or aspartate transaminase (AST) > 2.5 upper limit of normal (ULN) at randomization.
?Patients with severe cardiac insufficiency (NYHA, New York Heart Association classes 3 – 4).
?Patient has a history of sensitivity to rifaximin, rifampin, rifamycin antimicrobial agents, or any of the components of Rifaximin -EIR or placebo (see list in protocol at section 10.2.1).
?Patients with kidney failure at randomization.
?Any condition or circumstance that would prevent completion of the study or interfere with analysis of study results, including a history of drug or alcohol abuse, mental illness or non-compliance with treatments or visits, with immunological (including HIV infection), haematological, or neoplastic disease.
?Pregnant or nursing woman
?Patients who have donated 250 ml or more of blood in the last 3 months.
?Patients who have used any investigational drug (except biological therapies) within 3 months prior to screening.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To demonstrate the efficacy of Rifaximin –EIR 400 mg Tablet (800mg /BID, total daily dose 1600 mg) versus placebo in the prevention of endoscopic Crohn’s disease recurrence following ileocolonic resection.;<br> Secondary Objective: To demonstrate the efficacy of Rifaximin- EIR 400 mg Tablet (800mg /BID, total daily dose 1600 mg) versus placebo in the maintenance of clinical remission.<br> To evaluate the safety profile of Rifaximin-EIR 400 mg Tablet (800mg /BID, total daily dose 1600 mg)<br> Assess the effects of Rifaximin-EIR treatment on biological (inflammatory) markers of disease.<br> Evaluate the effects of Rifaximin -EIR treatment on quality of life<br> ;Primary end point(s): The primary end point of this trial will be the proportion of patients with endoscopic recurrence at 26 weeks after randomization defined as Rutgeerts score =i2.;Timepoint(s) of evaluation of this end point: 26 weeks
- Secondary Outcome Measures
Name Time Method