To evaluate the efficacy and safety of infliximab dose reduction guided by serial trough level measurements, compared to treatment as usual (no dose reduction), in Crohn*s disease patients who are in stable remission with infliximab maintenance…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Proportion of patients with sustained clinical remission
Secondary outcome
Proportion of patients with clinical and biochemical relapse; Time to relapse;
Presence of predictive factors for successful IFX dose reduction with specific
focus on smoking status, body mass index and extent of disease; Laboratory
tests (CRP and fecal calprotectin) at all study visits; Adverse events;
Economic evaluation; Pharmaco-economic evaluation; Quality of life; Yearly
total IFX dose per patient.
Background summary
Recent observations suggest that not all Crohn*s disease (CD) patients who are
in stable remission with infliximab (IFX) maintenance therapy may need the
recommended dose of 5 mg/kg, as long as IFX trough levels (TL) (e.g. serum drug
level measured just before the next administration) remain therapeutic
Study objective
To evaluate the efficacy and safety of infliximab dose reduction guided by
serial trough level measurements, compared to treatment as usual (no dose
reduction), in Crohn*s disease patients who are in stable remission with
infliximab maintenance therapy.
Study design
Single-blind prospective controlled randomized trial.
Intervention
Patients in the intervention arm will undergo stepwise dose reduction of IFX.
IFX dose will be decreased by 1 mg/kg, every 16 weeks. Dose reduction ends in
case of one or more of the following:
-Relapse, defined as:
- Rise of *3 points (compared to baseline) of total HBI score to a value of >4
(clinical relapse) in combination with CRP >5 mg/l - AND/OR calpro >250
measured at previous infusion visit
-AND/OR IFX TL <7 prior to the latest infusion.
Patients in the control arm will receive continued IFX at 5 mg/kg at an 8 week
interval.
Study burden and risks
Participation will result in additional blood sampling, since TLs will be
measured every 8 weeks. However, no additional venous punctures will be
performed, since blood sampling is performed directly before IFX infusion. All
other laboratory tests can be considered as routine care. No additional
hospital visits are required.
Current evidence indicates that TLs >3 suffice, and dose reduction will be only
performed when TLs remain >7. We expect that IFX dose reduction while
maintaining adequate TLs is not associated with an increased risk of relapse.
Moreover, we hypothesize that reducing IFX dose in patients with
supratherapeutic TLs, will lead to less side effects.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
-Diagnosis of CD based on endoscopy and pathology
-18 years or older
-At least 6 months in remission, defined as:
---Harvey Bradshaw Index *4,
---Normal serum C-reactive protein (CRP) level (<5 mg/l), and
---Low fecal calprotectin level (< 250 ug/g)
-IFX therapy >6 months at 5 mg/kg every 8 weeks with or without concomitant immunosuppression (stable for > 3 months).
-IFX TL > 7 ug/ml.
Exclusion criteria
-Non-adherence to the 8 weekly infusions schedule in the past
-Participation in another therapeutic trial
-Prior dose adjustments or interval shortening of IFX
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-001029-17-NL |
| CCMO | NL48325.018.14 |
| OMON | NL-OMON22458 |