Two Therapeutic Strategies for the Maintenance of Remission in Patients With Ulcerative Colitis

Phase 4

• Conditions: Colitis, Ulcerative
• Interventions: Drug: Azathioprine; Drug: Infliximab

• Registration Number: NCT03151525
• Lead Sponsor: Istituto Clinico Humanitas

Brief Summary

Ulcerative colitis patients treated with Infliximab (IFX) in deep remission after at least 12 months of treatment will be randomized to continue IFX or to stop IFX and start Azathioprine (AZA).

Each patient will be followed for 12 months.

Detailed Description

All eligible subjects will be able to participate in the study at any infusion occurred after 12 months since the beginning. They will be screened by medical history, physical examination, blood and faecal tests (included C-reactive protein and faecal calprotectin), as required by clinical practice. No children, pregnant or breastfeeding women, or elder subjects will be included. A colonoscopy + biopsies in the area of greater inflammation will be performed within ± 3 weeks since the baseline visit. The subjects can then be randomized and receive their first dose of study medication.

Subjects will be then evaluated every 8 weeks for the following 12 months from the randomization. Clinical and blood tests will be performed, and the partial Mayo Score will be calculated at each visit, until the final visit, when a new colonoscopy with biopsies will be repeated and the global Mayo Score will be evaluated. At final visit a new faecal sample for calprotectin will be collected.

Safety of the study treatments will be evaluated at each study visit. In case of study agent discontinuation, the patient will be managed according to usual practice and followed for the entire study period. Patients randomized in AZA arm, could restart IFX.

Study Timeline

• Status Verified: 2017-05
• Study Start: 2017-05-08
• Study First Submitted: 2017-05-08
• Study First Submitted QC: 2017-05-10
• Last Update Submitted: 2017-05-10
• Study First Posted: 2017-05-12
• Last Update Posted: 2017-05-12
• Primary Completion: 2019-10-03
• Study Completion: 2020-04-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Age 18 -65 years
• Written informed consent and willing to adhere to study procedures.
• Therapy with infliximab since at least 12 months, with one infusion every 8 weeks (a maximum interval between two infusions of ± 3 weeks is allowed)
• Sustained steroid-free remission in the last 6 months prior to inclusion, except for use of steroids as a preventive measure for infliximab infusion reaction, if required by local guidelines.
• Global Mayo score at baseline ≤ 2
• All Mayo subscores ≤ 1
• Absence of rectal bleeding
• Effective methods to avoid pregnancy during the study period

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Exclusion Criteria

• Disabling and persisting extraintestinal manifestation at baseline
• Patients unable to comply with study procedures
• Known intolerance or previous allergic reaction to thiopurines
• Concomitant therapy with allopurinol
• Any disease not compatible with the use of infliximab or azathioprine, as per clinician's judgement.
• Need for dose escalation of infliximab in the last 12 months prior to baseline.
• White blood cell count < 3000/mmc or absolute clinically relevant lymphopenia at baseline
• Active pregnancy or breastfeeding; willing for pregnancy during the study period

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Azathioprine	Azathioprine	Azathioprine 2-2.5 mg/kg/day, according to approved indication
Infliximab	Infliximab	Infliximab 5 mg/kg every 8 weeks

Primary Outcome Measures

Name	Time	Method
Relapse rate	12 months	relapse rate in the two study groups.

Secondary Outcome Measures

Name	Time	Method
Number of adverse events [Safety and Tolerability]	12 months	Number of adverse events of the two study strategies
Number of serious adverse events [Safety and Tolerability]	12 months	Number of serious adverse events of the two study strategies
Relapse time	12 months	Mean time to relapse in the two groups
Identification of potential risk factors for relapse. Age, sex, smoking habits, histological healing of mucosa and each Mayo subscore at baseline will be examined	12 months	Potential risk factor for relapse will be evaluated by univariable analysis, and a multivariable analysis will be performed for all factors with p\<0.30. Risk factors will be also analysed by logistic regression. Analysis of predetermined baseline characteristics (age, sex, smoking habits, histological healing of mucosa at baseline, and each Mayo subscore (stool number, presence of blood, colonic ulcerations) excluding the physician global assessment) to identify predictive factors for relapse.

Trial Locations

Locations (1)

IBD Center; 🇮🇹 Rozzano, MI, Italy