Course of the clinical trial - Two study groups
Course of the clinical trial
As a (potential) participant of this clinical trial, you have been diagnosed with Crohn's disease and have recently undergone a procedure in which the transition of the small intestine to the large intestine was removed. We call this procedure an ileocolonic resection. As you know, this surgical procedure is not a definitive solution for Crohn's disease. In many cases, endoscopic lesions reappear after a few months at the level of the new connection between the small and large intestine. Depending on the severity of these endoscopic lesions, they can give rise to new symptoms and complications over time, which sometimes requires another intervention. At the moment, it is not clear which approach is best to take in order to prevent the patient from developing Crohn's disease symptoms again after such an intervention. Do we start treatment with a biological therapy immediately after surgery, or can we wait for a first endoscopic re-evalution and initiate biological therapy only in those patients with clear endoscopic disease recurrence (relapse with endoscopic lesions)? Both options are already being used in clinical practice, but it is still not clear which approach is best, in terms of clinical outcome, potential side effects, quality of life, and cost to society.
We are conducting this clinical trial to compare these two approaches after ileocolonic resection and to decide which approach should take preference in daily clinical practice. In concrete terms, this means that after your surgery, you will either start biological therapy immediately, or you will only start biological therapy if a clear endoscopic disease recurrence is detected during a colonoscopy that is routinely scheduled about six months after the surgery. In both cases, you will undergo two colonoscopies to check whether lesions have formed (one after six months and one after eighteen months).
The type of biological therapy - adalimumab, infliximab, ustekinumab, vedolizumab or risankizumab - will be decided by you and your treating physician at the start of the clinical trial. If you end up in the study group where development of endoscopic disease recurrence is the trigger for initiating biological therapy, the chosen therapy will only be initiated at that time. The administration of the biological therapy depends on the chosen medication and will be administered via subcutaneous injection or intravenous infusion. The dose and frequency of administration of the biological therapy follows a standard schedule that the doctor will go over with you. If it proves necessary, the biological therapy will be optimized to suit your needs during the trial.
Participants are randomly assigned to two research groups that are compared. Each participant has an equal chance of being in one or the other research group, but cannot choose which group to be in. This study will be conducted in 23 Belgian hospitals and will involve approximately 300 participants. During the first 1,5 years of the clinical trial, there will be seven standard study visits, supplemented by additional visits when necessary. Afterwards, there will be a standard follow-up by your doctor for at least three years, with one study visit per year.
Study visits
Legend
X = Study specific, free of charge to participant.
X = Standard of care, participant pays for him/herself.
() = Optional
Additional visit (optional) = This is an additional visit that will be scheduled in case of any serious side effects or clinical symptoms.
Informed consent = The study cannot begin until "the informed consent" has been read, understood and signed by the participant and the research physician.
Incluson and exclusion criteria = These are the conditions that must be met by the participant in order to start participating in the study.
Randomization participant = Participants will be randomly assigned to one of the two study groups.
Clinical trial = Blood pressure, heart rate, body temperature and body weight are noted at each visit. Height is only measured during the first visit. An examination of the abdomen and any abnormalities in other areas is also performed every time. Latent tuberculosis is checked during visit 1 or visit 4, depending on when biological therapy is started. If latent tuberculosis is detected, it will be treated before starting biological therapy.
Data collection & questionnaire completion = All kinds of data such as age, gender, medical history, clinical and surgical features and Crohn's disease related symptoms will be collected. You will also complete questionnaires on disease activity, quality of life, work productivity and daily activity.
Note (changes in) Corhn's related therapy = Mesalamine, local and systemic steroids, thiopurines (azathioprine, mercaptopurine, thioguanine), methotrexate, anti-TNF medications (adalimumab, certolizumab pegol, infliximab), ustekinumab, vedolizumab, risankizumab, antibiotics and probiotics.
Start or optimization of biological therapy = When you are in group 1, you will start biological therapy on visit 2 and if necessary, therapy can be optimized starting on visit 4. If you are in group 2, you can start biological therapy in the presence of endoscopic lesions on visit 4. Therapy can also be optimized afterwards if it appears necessary.
Blood samples = Standard analysis of blood samples at each study visit.
Stool samples = From visit 2 onwards, these samples are used to measure the calprotectin content of the stool. For the sample of visit 4 and 7, the sample should already be taken two or three days in advance (i.e. before starting the bowel preparation needed for the colonoscopy) and kept at room temperature.
Check adverse events = Serious adverse events during the study are noted and treated.
Colonoscopy = During study visits 4 and 7, the participant undergoes a colonoscopy to determine if new postoperative lesions have developed (endoscopic disease recurrence). A third colonoscopy may be scheduled if deemed necessary by the treating physician (visit 8). The endoscopic images of all participants will be coded and forwarded to an external expert to further improve the endoscopic activity score.
Additional serum sample for patients on biological therapy for the PK-PD substudy (optional) = If you are participating in the PK-PD substudy, an additional serum sample will be taken during three to four study visits while you are being treated with biological therapy. A sample will only be taken at four of the five indicated times.
Note: The four study visits without colonoscopy (visit 1, visit 2 in week 0, visit 3 in week 14, visit 5 in week 46 and visit 6 in week 62) last about half a day. The two study visits with colonoscopy (visit 4 in week 30 and visit 7 in week 86) will take approximately a day. This is comparable with the standard visits in the hospital if you would not participate in the study.
If you meet all the requirements and decide to participate in the study, you will undergo the tests and examinations listed above. In the case of significant side effects, the investigator may deem it necessary to perform additional tests, which will then be consideren standard care. The treatments and examinations that are study specific are indicated in bold in the box and will be paid for by the sponsor, and you will not be charged. The treatments and examinations which are part of your standard treatment will be charged to you or your mutual insurance company (Belgian social security).