Post-operative endoscopic Crohn’s disease recurrence MedDRA version: 20.0 Level: LLT Classification code 10013099 Term: Disease Crohns System Organ Class: 100000004856
Conditions
Sponsors
ALFASIGMA S.P.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ? 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
Exclusion criteria
Exclusion criteria: ? 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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.; 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. To evaluate the safety profile of Rifaximin-EIR 400 mg Tablet (800mg /BID, total daily dose 1600 mg) Assess the effects of Rifaximin-EIR treatment on biological (inflammatory) markers of disease. Evaluate the effects of Rifaximin -EIR treatment on quality of life ;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
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? Patients with endoscopic Rutgeerts score 220 points; CDAI will be assessed at each visit). ? Proportion of patients with clinical symptom remission according to PRO defined by (1) the total number of liquid/very soft stools for the 7 days prior to each visit being = 10 (from CDAI Item 1); AND (2) an abdominal pain rating of = 1(from CDAI Item 2) on each day for the 7 days prior to each visit. ? Development of a new/re-draining fistula or abscess by week 26 ? Time to clinical recurrence ? Change from baseline in CRP and faecal calprotectin at each visit during the Treatment Period. ? Change from baseline in indices of health outcomes (SF-36®) at Week 26. ? Assessments of safety will be based on the following: - vital signs (including blood pressure, pulse, temperature and body weight); - routine laboratory parameters (haematology, chemistry, urinalysis); - adverse events; - withdraw due to adverse events (AEs). ; Timepoint(s) of evaluation of this end point: At week26 4-8-16-26-28 weeks 4-8-16-26-28 weeks At week26 At week26 4-8-16-26-28 weeks 4-8-16-26-28 weeks At randomization visit, week 4-8-16-26-28 | — |
Countries
Belgium, Germany, Netherlands, Spain
Contacts
Public ContactCecilia Renzulli
ALFASIGMA S.P.A.
Outcome results
None listed