Maarten Cozijnsen

58 Methods Trial design We designed an international multicenter open-label randomized controlled trial (RCT) with two parallel treatment arms.(Figure 1) In addition, one of these arms (step-up) contains two initial treatment options to choose from (prednisolone and EEN). This decision is made by the treating physician together with the patient and/or parents. This allocation based on choice was chosen over randomized allocation, because of two reasons. Firstly, this choice mimics the current clinical practice of the step-up strategy and is therefore a better comparator. Secondly, a strong aversion to one of the step-up treatment may prevent patients from participating in this trial. Relapse? Azathioprine IFX infusions Top-down Azathioprine Prednisolone or EEN Step-up Randomisation Endoscopy 10 260 0 52 Screening Inclusion 3-17 years of age untreated Crohn wPCDAI>40 Exclusion Need for surgery Severe comorbidity Active perianal fistula Opt. endoscopy IFX infusions Relapse? IFX infusions Figure 1. TISKids study design IFX = infliximab; EEN = Exclusive Enteral Nutrition; wPCDAI = weighted Pediatric Crohn’s Disease Activity Index (25) Eligible patients willing to participate in this trial will be randomized with concealed group allocation, resulting in two comparable groups. Although a double-blind design is considered ideal for treatment comparison, an open-label design was chosen instead, because the former was not feasible due to the use of three treatments with different routes of administration – IFX is given intravenously, prednisolone are tablets and EEN is a liquid formula either ingested by mouth or by nasogastric tube – which makes using placebos very complex and costly. As a consequence of the open-label design, our results could potentially be influenced by performance bias and detection bias. However, since a double-blind design is not feasible, our open-label RCT is the optimal design for this research question.