Evaluating treatment to a target of transmural healing in patients with moderately to severely active Crohn’s disease: rationale, design and protocol for the randomised controlled VECTORS trial

INTRODUCTION: The optimal treatment target for Crohn's disease (CD) is unknown. Targeting transmural healing (TMH) may be associated with a lower risk of complications than clinical and endoscopic outcomes. The Study to Evaluate Transmural Healing as a Treatment Target in Crohn's Disease (VECTORS) aims to investigate TMH as a potential treatment target and its long-term benefits in patients with CD. METHODS AND ANALYSIS: VECTORS is a phase 4, interventional, parallel-group, multicentre, randomised controlled trial. Approximately 304 adult patients with moderately to severely active CD from multiple international sites will be enrolled and randomly assigned in a 1:1 ratio to treatment target group 1 (corticosteroid-free intestinal ultrasound-based response or TMH plus clinical and biomarker remission) or group 2 (corticosteroid-free clinical and biomarker remission). All patients receive vedolizumab according to the standard dosing regimen, with an additional dose at week 10, followed by a treatment escalation algorithm to reach the assigned targets. Randomisation will be stratified by prior advanced therapy exposure, disease location and disease duration. The primary objective is to determine if treatment target group 1 is superior to group 2 for the primary efficacy outcome of corticosteroid-free endoscopic remission at week 48. CD-related complications (key secondary outcome) are assessed at week 96. ETHICS AND DISSEMINATION: The trial is conducted in compliance with the protocol and applicable regulatory requirements and is approved by institutional review boards/independent ethics committees at the country or site level. Patients' written informed consents are obtained and documented prior to trial participation. Findings will be disseminated in peer-reviewed journals and at scientific congresses. TRIAL REGISTRATION NUMBERS: NCT06257706; EUCT, 2023-509096-16-00.