Reduce Risk for Crohn's Disease Patients

• Register: ClinicalTrials.gov
• Last refreshed on: 10 February 2025
• Main ID: NCT02852694
• Date of registration: 09/06/2016
• Prospective Registration: Yes
• Primary sponsor: PIBD-Net
• Public title: Reduce Risk for Crohn's Disease Patients RCT
• Scientific title: Risk-stratified Randomized Controlled Trial in Paediatric Crohn Disease:Methotrexate Vs Azathioprine or Adalimumab for Maintaining Remission in Patients At Low or High Risk for Aggressive Disease Course, Respectively-a Treatment Strategy
• Date of first enrolment: February 28, 2017
• Target sample size: 192
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT02852694
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 4

Countries of recruitment

France

Contacts

• Name: Frank RUEMMELE, PhD / MD
• Affiliation: PIBD-Net

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Children 6-17, with a new-onset Crohn Disease diagnosed using established criteria
(37, 38), requiring a steroid-based or Enteral nutrition based induction therapy

2. At initial diagnosis, wPCDAI >40 or CRP>2 times upper limit at diagnosis

3. all wPCDAI scores (0-120) are possible at inclusion (patients in remission and
patients with active disease)

4. Luminal active Crohn Disease (B1) with or without B2 and/or B3 disease behavior

5. Initial exposure to 5-ASA and derivate is tolerated

6. Exposure to antibiotics is tolerated

7. If one of the following criteria is present, patients are allocated to the high risk
group prior randomization:

- Complex fistulizing perianal disease

- Panenteric disease phenotype (defined as L3 with L4b per Paris classification
or L3 with deep ulcers in duodenum, stomach or oesophagus (not HP (helicobacter
pylori)- or NSAID-related))

- Severe growth impairment (height z-score <-2 or crossing 2 percentiles or more)
likely related to CD

- Significant hypoalbuminemia (<30g/l), elevated C reactive protein (CRP) (at
least 2 times above normal range), or wPCDAI >12.5 despite 3 weeks of optimized
induction therapy with steroids or Exclusive enteral nutrition

- B2, B3 or B2B3 disease behavior

- Overall cumulative disease extend of =60 cm

8. Informed and signed consent

Exclusion Criteria:

1. Patients with wPCDAI<42,5 at initial diagnosis, except if CRP>2 times upper limit

2. No induction therapy with steroids or enteral nutrition

3. Previous therapy with any IBD (inflammatory bowel desease) -related medications
other than induction therapy as detailed in this protocol (except 5-ASA).

4. Pregnancy or refusal to use contraceptives during the study period in pubertal
patients (both boys and girls) unless absolute abstinence (no sexual activity) is
confirmed at each study visit. Positive pregnancy testing throughout the study will
trigger prompt withdrawal of the patient from the study.

5. Lactating mothers

6. Children with perianal fistulising disease who require surgical therapy (drainage,
seton placement)

7. Patients homozygous for Thiopurine methyl transferase or those with Thiopurine
methyl transferase activity <6 nmol/h/ml erythrocytes or <9nmol 6MTG (6
methylthioguanine/g Hb/h), unless they qualify as high risk patients

8. Evidence of un-drained and un-controlled abscess/phlegmon

9. Contraindication to any drugs used in the trial (including
intolerance/hypersensitivity or allergy to either study drug (thiopurines,
methotrexate or adalimumab))

10. Current or previous malignancy

11. Serious comorbidities (such as renal insufficiency, hepatitis, respiratory
insufficiency) interfering with drug therapy or interpretation of outcome parameters
or will make it unlikely that the patients will finish the trial.

12. Infection with mycobacterium tuberculosis

13. Moderate to severe heart failure (NYHA classe III/IV)

14. Oral anticoagulant therapy, anti-malaria therapy

15. Live vaccines exposure (including yellow fever) less than 3 weeks prior inclusion


Age minimum: 6 Years
Age maximum: 17 Years
Gender: All

Health Condition(s) or Problem(s) studied

Crohn's Disease

Intervention(s)

Drug: Azathioprine / 6 Mercaptopurine

Drug: Adalimumab

Drug: Methotrexate

Primary Outcome(s)

Rate of sustained steroid/EEN-free remission at Month 12 [Time Frame: Month 12]

Secondary Outcome(s)

Linear height velocity [Time Frame: 12 months]

Questionnaire : health-related life of quality (IMPACT 3) between the different treatment arms [Time Frame: 12 months]

Steroid sparing effect of the regimens [Time Frame: 12 months]

Remission at 12 weeks (measured by wPCDAI [Time Frame: 12 weeks]

Anti-adalimumab antibodies monitoring : concentration of anti-adalimumab antibodies in relation to adherence, toxicity and response [Time Frame: 12 months]

Clinical predictors for response, including genomic and serological markers [Time Frame: 12 months]

DNA pharmacogenetics (multiplex genotyping of polymorphism in drug metabolism) in relation to toxicity and response to therapy [Time Frame: 12 months]

Time to first relapse [Time Frame: Month 12]

Questionnaire : TUMMY-CD (patient reported outcome) at month 12 [Time Frame: 12 months]

Questionnaire : School Attendance (patient reported outcome) at month 12 [Time Frame: 12 months]

6 Mercaptopurine and azathioprine metabolites monitoring : concentration of metabolites in relation to adherence, toxicity and response [Time Frame: 12 months]

Comparison of toxicity of the different protocol drugs [Time Frame: 12 months]

Concentration of protocol drug (ADA or MTX) monitoring in relation to adherence, toxicity and response [Time Frame: 12 months]

Predictive value of fecal calprotectin levels, CRP and other serum tests [Time Frame: 12 months]

Questionnaire : WPAI:CD Caregiver (patient reported outcome) at month 12 [Time Frame: 12 months]

Secondary ID(s)

2016-01

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

European Commission