About the Trial
Sustained surgery and steroid free remission from completion of steroid induction treatment through to week 48.
- Mucosal healing (SES-CD)
- Quality of life assessment (IBDQ & EQ-5D)
i) Number of flares
ii) Cumulative steroid exposure
iii) Steroid-free remission
iv) Number of hospital admissions and operations
- A full health economic evaluation will also be produced
We anticipate, that biomarker stratification, will allow demonstration of a large difference between “Top-Down” and “Accelerated Step-Up” in IBDhi (the individuals destined to have more severe disease) and only a small difference in IBDlo (individuals destined to have milder disease). This difference between the deltas will be the key outcome of interest and the basis for the PROFILE trial. If this can be demonstrated then we hope this biomarker can be used to help personalise care for patients with Crohn’s disease.
- Crohn’s disease diagnosed within 6 months* using standard endoscopic, histologic or radiological criteria.**
- Clinical evidence of active Crohn’s disease (corresponding to a HBI greater than or equal to 7)***
- Endoscopic evidence of at least moderately active disease****.
- CRP > upper limit of normal on local assay OR calprotectin >200ug/g*****.
- Immunomodulator and anti-TNF naive.
- Aged 16-80 years old.
* Patients with newly-diagnosed patchy colonic inflammation, initially diagnosed as indeterminate colitis, would meet inclusion criteria for the trial if felt to be consistent with Crohn’s disease.
** Patients need to have discontinued systemic corticosteroids for one week or more prior to screening assessments and still have ongoing, active disease.
*** Patients with an HBI score of ≥ 7 within 2 weeks of screening visit would be eligible for inclusion.
**** Grading of severity will be based on clinical impression of endoscopist or clinical team managing Crohn's disease and as a guide would correspond to an approximate SES-CD of 4 or more for ileal-only disease and score of approximately 6 or more for ileocolonic or colonic disease distributions.
Endoscopic results used for confirming inclusion can be from the participants index colonoscopy performed as part of their standard care. Ideally however, a video of the index colonoscopy should be recorded wherever possible. If this is not possible, photos of the colonoscopy or colonoscopy report can be used to confirm inclusion. Results from capsule endoscopies and flexible sigmoidoscopy are also permitted to confirm inclusion.
***** Results of blood tests and faecal calprotectin performed as part of standard care can be used for eligibility provided performed up to 3 months prior to the baseline visit – however a repeat stool sample should still be sent for central processing (as central laboratory results will be used in subsequent analyses). Sample pot for faecal calprotectin will be provided at screening visit and patients advised to provide sample promptly so that central calprotectin result is available at the baseline visit.
- Ulcerative colitis
- Fistulating peri-anal Crohn’s disease or active perianal sepsis sufficient to mandate anti-TNF therapy
- Patients with obstructive symptoms AND evidence of a fixed stricture on radiology or colonoscopy, which suggest that the patient is at high risk of requiring surgery over the following year. N.B. patients with modest degrees of stricturing on imaging but no obstructive symptoms may be included according to clinician judgement.
- Contra-indication to trial medications.
- Patients with active malignancy or recent malignancy with clinically estimated high risk of recurrence
- Pregnant/breastfeeding at screening
- Other serious medical or psychiatric illness.
- Unable to comply with protocol requirements (including alcohol and/or recreational drug abuse).
Page last updated: 22nd March 2021