A Randomized, Multicenter Open Label Study Comparing Early Administration of Azathioprine Plus Infliximab to Corticosteroids Plus Azathioprine for Acute Severe Colitis
Overview
- Phase
- Phase 4
- Intervention
- Azathioprine
- Conditions
- Ulcerative Colitis
- Sponsor
- Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
- Enrollment
- 65
- Locations
- 16
- Primary Endpoint
- Percentage of patients with treatment failure at week 52.
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
PHASE : IV TYPE OF STUDY : With direct benefit. DESCRIPTIVE : Multicentre, randomized, open label study. INCLUSION CRITERIA : Acute severe ulcerative colitis. OBJECTIVES : To compare the efficacy and safety of early administration of the combination therapy with infliximab and azathioprine with steroids and azathioprine in patients with acute severe ulcerative colitis treated with intravenous steroids.
STUDY TREATMENTS : All patients :
Intravenous steroids (0.8 mg/kg/day of methylprednisolone or equivalent) for 5 days.
Combination therapy arm:
Infliximab 5 mg/kg plus Azathioprine 2-2.5 mg/kg/day.
Azathioprine arm:
Steroids tapering for 3 months and Azathioprine 2-2.5 mg/kg/day.
Detailed Description
NUMBER OF PATIENTS : 73 patients in each group i.e. a total of 146patients. RECRUITMENT PERIOD : 36 months STUDY DURATION : 12 months PRIMARY END POINT : Treatment failure is defined by: * Absence of steroid-free remission at W52 according to the total Mayo Disease Activity Index score * OR Absence of mucosal healing (Mayo endoscopic subscore 0-1) * OR Adverse event leading to treatment interruption * OR Colectomy * OR Death * OR Infliximab withdrawal in the combination therapy group OR Infliximab introduction in the azathioprine group SECONDARY END POINT: - Clinical response and remission at D7, W14 and W52 (according to Lichtiger score and total Mayo Disease Activity Index score) * Endoscopic and histological response * Mucosal healing (partial endoscopic Mayo subscore 0) * Colectomy rate * Adverse events rate * Fecal calprotectin * Health-economic outcome
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age \> 18 years.
- •Diagnosis of UC according to Lennard-Jones criteria (Appendix 1).
- •Endoscopically demonstrated colorectal lesions localized above the anal margin and extending at least up to 15cm proximally (Endoscopic Mayo subscore ≥ 2).
- •Acute flare requiring hospitalization
- •Severe acute flare of UC with a Lichtiger Index score \> 10 at Day -3
- •Adequate contraception for male or female subjects of childbearing potential, which will be continued throughout the study and at least 3 months after study termination.
- •3.2 EXCLUSION CRITERIA
- •Pregnant or breast-feeding woman.
- •Previous treatment with infliximab.
- •Treatment with adalimumab or golimumab within 8 weeks before randomization
Exclusion Criteria
- Not provided
Arms & Interventions
Combination therapy arm
Infliximab 5 mg/kg plus Azathioprine 2-2.5 mg/kg/day. Azathioprine will be introduced at day 5-7 and continued until week 52. Azathioprine dose regimen will be between 2 and 2.5 mg/kg/d, as close as possible to 2.5 mg/kg/d, or to 1.5 mg/kg/d for 6-mercaptopurine, in one daily intake.
Intervention: Azathioprine
Combination therapy arm
Infliximab 5 mg/kg plus Azathioprine 2-2.5 mg/kg/day. Azathioprine will be introduced at day 5-7 and continued until week 52. Azathioprine dose regimen will be between 2 and 2.5 mg/kg/d, as close as possible to 2.5 mg/kg/d, or to 1.5 mg/kg/d for 6-mercaptopurine, in one daily intake.
Intervention: Infliximab
Azathioprine arm
Intravenous steroids will be continue until day 2. Then, steroid therapy will be orally administered at a dose of 40-60 mg/day ou 1 mg/kg/day prednisolone (or equivalent) and progressively reduced by 10mg step every week to 20mg per day, and then reduced by 5mg step every week until stopped. Hydrocortisone intake to prevent steroid weaning will be authorized until supradrenal function normalization. In patients with clinical response at day 7, Azathioprine will be introduced at day 5-7 and continued until week 52. Azathioprine dose regimen will be between 2 and 2.5 mg/kg/d, as close as possible of 2.5 mg/kg/d, or of 1.5 mg/kg/d for 6-mercaptopurine, in one daily intake.
Intervention: Azathioprine
Azathioprine arm
Intravenous steroids will be continue until day 2. Then, steroid therapy will be orally administered at a dose of 40-60 mg/day ou 1 mg/kg/day prednisolone (or equivalent) and progressively reduced by 10mg step every week to 20mg per day, and then reduced by 5mg step every week until stopped. Hydrocortisone intake to prevent steroid weaning will be authorized until supradrenal function normalization. In patients with clinical response at day 7, Azathioprine will be introduced at day 5-7 and continued until week 52. Azathioprine dose regimen will be between 2 and 2.5 mg/kg/d, as close as possible of 2.5 mg/kg/d, or of 1.5 mg/kg/d for 6-mercaptopurine, in one daily intake.
Intervention: Prednisolone
Azathioprine arm
Intravenous steroids will be continue until day 2. Then, steroid therapy will be orally administered at a dose of 40-60 mg/day ou 1 mg/kg/day prednisolone (or equivalent) and progressively reduced by 10mg step every week to 20mg per day, and then reduced by 5mg step every week until stopped. Hydrocortisone intake to prevent steroid weaning will be authorized until supradrenal function normalization. In patients with clinical response at day 7, Azathioprine will be introduced at day 5-7 and continued until week 52. Azathioprine dose regimen will be between 2 and 2.5 mg/kg/d, as close as possible of 2.5 mg/kg/d, or of 1.5 mg/kg/d for 6-mercaptopurine, in one daily intake.
Intervention: Hydrocortisone
Outcomes
Primary Outcomes
Percentage of patients with treatment failure at week 52.
Time Frame: Week 52
Failure is defined as: * absence of steroid-free remission (Total Mayo Disease Activity Index (DAI) score ≤ 2 with no individual subscore \> 1) * absence of mucosal healing (Endoscopic Mayo DAI subscore ≤ 1) * or severe adverse event leading to treatment interruption between day 0 and week 52 * or colectomy between day 0 and week 52 * or fatality between day 0 and week 52 * or infliximab withdrawal for failure and /or intolerance in the combination therapy group * or any biological agent introduction in the azathioprine group
Secondary Outcomes
- Percentage of patients in clinical response at day 7(7 days)