Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT03209232 |
| Other study ID # |
INDUCE |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
April 16, 2018 |
| Est. completion date |
September 1, 2021 |
Study information
| Verified date |
September 2021 |
| Source |
Schneider Children's Medical Center, Israel |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Objectives: To examine the effect of accelerated infliximab induction in children with
moderate to severe UC. Design: A multi-center, prospective, randomized, open label study.
Setting: Pediatric gastroenterology centers. Participants: Children 6 year to 17 years
(Overall, 84 patients) with moderate to severe UC who are corticosteroid dependent/resistant
thus planned to receive infliximab induction. Intervention: Group 1 (intervention) will
receive an accelerated induction at 0,1,3 weeks (5 mg/kg) and then at week 7,11,15. Group 2
(standard) will receive a per protocol induction at 0,2,6 weeks (5 mg/kg) and then at week
14. Drug levels will be obtained prior to each infusion in each group (up to week 20).
Further maintenance will be planned according to drug levels at weeks 15 and 14,
respectively. Follow-up will continue without further interventions till 52 weeks following
induction. Main outcome measure: Clinical remission, on infliximab at week 20. Secondary
outcome measures: 1. Colectomy free rates at week 20 and 52. 2. Clinical remission on
infliximab at week 52. 3. Drug levels and anti-drug antibodies prior to last study infusion.
4. Anthropometric and laboratory measures including calprotectin at the end of induction,
week 20 and week 52 5. Changes in fecal microbiome, virome and bile acids content. Sample
size: In order to demonstrate 30% difference in clinical remission rate between groups is
significant, we will need to study 36 children in each group to be able to reject the null
hypothesis that the failure rates between the groups are equal with probability (power) of
80% and a type I error probability of 0.05.
Description:
General intervention scheme:
The decision to start IFX is the sole decision of the treating physician based on the
patient's immediate need. Eligible patients are those who are planned to start IFX. All
patients will undergo clinical and laboratory evaluation for IFX eligibility (PPD, infectious
serology). If the tests have already done in the last 3 months, we will use these data, there
is no need to repeat. Patients must have a negative stool culture, stool for parasites and
clostridium difficile toxin test performed over the last week in order to be eligible. The
screening visit may be performed concomitantly with the enrolment visit if all inclusion and
exclusion criteria are met.
Patients will be enrolled at the first screening visit. Informed consent will be signed by
both parents is required during enrollment. Informed assent will be offered for patients 14
years old and older. Eligible patients, ambulatory UC patients, requiring IFX for
corticosteroid dependent or refractory moderate to severe disease (excluding acute severe
UC), meeting inclusion/exclusion criteria, after obtaining informed consent, will be
randomized (1:1 ratio in blocks of four, stratified by immunomodulators use) at enrollment
visit (week 0, prior to IFX initiation) to either group 1 or group 2 using opaque, numbered
and sealed envelopes. Prior corticosteroid treatment is allowed as a taper-down schedule
during induction with IFX and must be terminated by week 10 (otherwise will be defined as
induction failure). At each visit all patients will be examined and have height, weight, and
PUCAI performed as well as comprehensive laboratory examinations including CBC, albumin, AST,
ALT, ESR and CRP (CRP will be measured and registered in mg/dL) and fecal samples (4 grams)
for bile acids and microbiome/virome. Fecal sample for fecal calprotectin (FC) will be
obtained as well at weeks 20 and 52. Extent of disease will be registered using the Paris
classification (Levine A et al, IBD, June 2011) and will be based on the latest colonoscopic
evaluation (described only by macroscopic involvement). Patients who undergo a colonoscopy at
any time as standard of care before initiating biologic therapy should register the results
of colonoscopy (according to the Mayo score- A score of ≤1 is considered complete mucosal
healing). In addition, every colonoscopy that will be performed during the study period based
on physician discretion, should be register in the CRF (Colonoscopy is not part of this
specific protocol).
The study period is composed of two distinctive phases: Intervention phase: week 0-20 and
follow-up phase: week 21-52.
Group 1 (intervention group): Patients in group 1 will receive an accelerated induction at
0,1,3 weeks (5 mg/kg) and then at week 7,11,15.
Group 2 (control group): Patients in group 2 will receive a per protocol induction at 0,2,6
weeks (5 mg/kg) and then at week 14.
Intensification by shortening intervals between infusion rather than dose increment was
chosen based on the pharmacokinetics of IFX in severe disease favoring this strategy in-order
to maintain adequate trough drug-levels and avoid intermittent exposure (23).
Drug levels will be obtained prior to each infusion in each group in the intervention phase.
Further maintenance will be planned according to drug levels at weeks 15 and 14,
respectively. A visit concluding the intervention phase will be performed at week 20. The
follow-up phase will continue without further interventions till week 52. During the
follow-up phase (maintenance) treatment will be administered according to the treating
physician discretion, with no restrictions.
Patients with induction failure in the control arm (defined as a lack of improvement of at
least 20 points from the baseline PUCAI score OR PUCAI≥35 at 3 weeks following induction)
will be able to undergo treatment intensification by decreasing infusion intervals according
to the treating physician discretion.
