Crohn's Colitis, Exacerbation of Ulcerative Colitis, Ulcerative Colitis, Active Severe
Conditions
Keywords
IBD: Inflammatory Bowel Diseases, CD: Crohn's Disease, UC: Ulcerative Colitis, ASC: Acute Severe Colitis, FMT: Fecal Microbiota Transplantation, PUCAI: Pediatric Ulcerative Colitis Activity Index, Ciprofloxacin, Doxycycline, Gentamycin, amoxicillin, vancomycin, metronidazole,ciprofloxacin
Brief summary
the etiology of Inflammatory Bowel Diseases (IBD) is closely associated with the gut microbiome. The results of previous studies on the effectiveness of antibiotics and fecal macrobiota transplantation (FMT) are contradicting. Aims: to evaluate the effectiveness of wide-spectrum antibiotic regimens in acute severe colitis in an addition to standard corticosteroid therapy (UC and isolated UC-like Crohn's colitis). The secondary aim is to assess the outcome of FMT in those not responding to five days of therapy (in either arm). As an exploratory aim, any IBD patient with a resistant disease to at least two immunosuppressive medications, may be treated with either interventions.
Interventions
DRUGAB (antibiotics)
1. PO Vancomycin 250mgX4/d for 3 weeks 2. PO Amoxycillin 50mg/Kg divided by 3 (up to 500mgX3/d) - for 3 weeks 3. PO Doxycycline 2mg/kg X2/d (up to 100mgX2/d) - for 3 weeks; OR- For children younger than 8 years: PO Ciprofloxacin 10mg/Kg X2/2 (up to 250mgX2/d) for 3 weeks Patients with known allergy to one of the drugs may be treated with oral Gentamycin (2.5mg/KgX3/d) for 3 weeks instead of the allergenic drug.
DRUGCS (corticosteroids) Only
1. methylprednisolone (1.5mg/kg up to 60mg daily in two divided doses) 2. PO Metronidazole 5mg/Kg X3/d (up to 250mgX3/d) - for 3 weeks
Sponsors
Shaare Zedek Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Children over the age the 2 years and adults of all ages with established diagnosis of UC using standard criteria (26, 27). * Admission for IV steroid therapy * PUCAI of at least 65 points at admission (i.e. severe attack) * PUCAI\>45 at enrollment * Ability to swallow antibiotics (pills or syrup)
Exclusion criteria
* Change in dose or intervals of anti-TNF within the past 2 months prior to admission. * Disease confined to the rectum (Proctitis). * Antibiotic use in the past 4 weeks. * Any known erosive inflammation anywhere in the small bowel or esophagus. * Any proven infection such as positive stool culture, parasite or C. difficile, urinary tract infection, cellulitis, abscess, pneumonia, line-infections etc. * Fever \>38.5, or \>38.0c thought to be unrelated to the inflammatory process of active UC. * The probable need for second line medical therapy (infliximab, cyclosporine, tacrolimus) or colectomy within 5 days of enrollment, as judged by the caring physician. * Known allergy to more than one antibiotic regimen from the list below. * Pregnancy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Total PUCAI (Pediatric Ulcerative Colitis Activity Index) score | at day 5 after treatment (compared between the two treatment groups). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in microbiome pattern. | 3 years from baseline | — |
| Rate of C. difficile infection | at days 5 and 14 after treatment. | — |
| Need for subsequent admission | by 1 year | — |
| Calprotectin levels | at 5 and 14 days after treatment. | — |
| Rate of gastrointestinal carriage of resistant organisms (VRE, ESBL) | at days 5 and 14 after treatment. | — |
| Number of patients with PUCAI<35 points | at day 5 | without the need for second line therapy (anti TNF, cyclosporine or tacrolimus) or colectomy. |
| The need for second line therapy or colectomy by discharge | by 90 days and at 1 year | — |
| Rate of steroid | dependency at 1 year | defined as a course longer than 3 month with an unsuccessful attempt to wean steroids or cumulative steroid treatment months of 4 months, during the year. |
| Remission rates | at days 7, separately at discharge, separately at day 14, and separately at 90 days. | defined by PUCAI\<10 without the need for second line therapy (anti TNF (Tumor Necrosis Factor), cyclosporine or tacrolimus) or colectomy. |
Countries
Canada, Finland, Israel, Italy, Poland, Spain
Outcome results
None listed