Colitis, Ulcerative Clinical Trial
Official title:
Conventional Step-Up Versus Infliximab Monotherapy in Patients With Active Moderate to Severe Ulcerative Colitis. A Randomized, Open Label, Prospective, Multicenter Study
This study will be performed to compare the efficacy and safety of the classical "Step-Up" approach for treatment of moderate-to-severe active ulcerative colitis using oral prednisolone + oral 5-aminosalicylic acid (5-ASA) or oral prednisolone + oral azathioprine (AZA) with a more intensive and early "Top-Hold" approach with intravenous infliximab (5 mg/kg) administered at Weeks 0, 2, and 6 and 8 weeks thereafter.
Participants will be randomized to receive either intravenous (IV) infliximab monotherapy
(Top-Hold approach) starting at a dose of 5 mg/kg at Weeks 0, 2, and 6 and thereafter every
8 weeks in Level 1, or classical Step-Up treatment starting with oral prednisolone (40
mg/day for at least 3 days and at most 2 weeks followed by 1 mg/kg/day for a minimum of 7
days and up to 2 weeks in the case the participant does not show an improvement in clinical
symptoms under 40 mg/day treatment) + oral 5-aminosalicylic acid (5-ASA) at a dose of 2
g/day in Level 1.
Participants receiving Step-Up treatment who have not achieved adequate response during the
first 4 weeks of prednisolone treatment will directly enter Level 3 treatment after
endoscopy is performed to confirm treatment eligibility. Furthermore, participants that have
not achieved response at Week 4 will also directly enter Level 3 and be switched to
treatment with IV infliximab.
If a participant experiences a first flare after initial response, participants in the
Step-Up group will start prednisolone treatment at the last effective dose (i.e.,
participants that previously responded to prednisolone 40 mg/day will receive a dose of 40
mg/day for at least 3 days and up to 2 weeks; participants that previously responded to
prednisolone 1 mg/kg/day will receive a dose of 1 mg/kg/day for a minimum of 7 days and up
to 2 weeks). If the last effective dose was 40 mg/day and the participant does not respond
within 14 days, the dose will be adjusted to 1 mg/kg/day for a minimum of 7 days and up to 2
weeks. In case the participant does not respond to prednisolone (i.e., does not return to
their individual baseline partial Mayo score obtained at study Week 4), the participant will
enter Level 3 and receive treatment with IV infliximab.
If a participant experiences a second flare after initial response at Week 4 (Level 1), the
participant will enter treatment Level 2. In Level 2, participants will receive a
prednisolone induction at the same effective dose as previously used in Level 1 +
maintenance treatment with oral azathioprine (AZA) at a dose of 2.0-2.5 mg/kg/day.
Participants that do not respond to this treatment at Level 2 or that develop a further
flare after initial response at Level 2 will enter Level 3 and will receive treatment with
IV infliximab following endoscopy to confirm treatment eligibility.
If at any time during treatment, a participant becomes prednisolone dependent (i.e., flare
during tapering phase of prednisolone), the participant will enter Level 3 treatment with IV
infliximab.
Participants in Level 1 of the Top-Hold treatment group (IV infliximab at Week 0, 2, and 6
and every 8 weeks thereafter) that have not achieved response at Week 4 will receive IV
infliximab 5 mg/kg at reduced intervals of 4 weeks (Level 2) starting with the Week 10
infusion. Participants suffering a flare after initial response in Level 1 will be switched
to to Level 2. Participants that do not respond to treatment at reduced intervals after 3
infusions (12 weeks), or that develop a further flare after initial response at Level 2,
will be switched to treatment with oral prednisolone + AZA (Level 3) following colonoscopy
to confirm eligibility.
When a participant responds to treatment with IV infliximab in Level 2, they will return to
treatment with IV infliximab every 8 weeks when response is achieved at 3 consecutive
visits.
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Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
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