Specific objectives and outcome measures of the VERDICT trial
| Primary objective | Primary outcome measure | Population(s) |
| To determine whether a treatment target of corticosteroid-free symptomatic, endoscopic and histologic remission (group 3) is superior to corticosteroid-free symptomatic remission (group 1) | Time from treatment target achievement to a UC-related complication* | Achieved-target population† |
| Secondary objectives | Secondary outcome measures | Population(s) |
| 1. To evaluate time to a UC-related complication in all randomised patients including subgroups on and off corticosteroids at the time of achieving other relevant components of the treatment target | Time from treatment target achievement to a UC-related complication* | All randomised patients |
| 2. To determine whether a treatment target of corticosteroid-free symptomatic and endoscopic remission (group 2) is superior to corticosteroid-free symptomatic remission (group 1) | Time from treatment target achievement to a UC-related complication* | All randomised patients, achieved-target population† |
| 3. To determine whether a treatment target of corticosteroid-free symptomatic, endoscopic and histologic remission (group 3) is superior to corticosteroid-free symptomatic and endoscopic remission (group 2) | Time from treatment target achievement to a UC-related complication* | All randomised patients, achieved-target population† |
| 4. To evaluate the time to a UC-related complication in the subgroup of patients who exclusively achieve their treatment target and not a higher target by week 48 | Time from treatment target achievement to a UC-related complication* | Achieved-target population† |
| 5. To assess the time to achieve the respective treatment targets among the randomised groups‡ | Time to treatment target achievement | Achieved-target population† |
| 6. To evaluate the time to each type of UC-related complication across the treatment target groups | Time to hospitalisation, colectomy, rescue therapy, treatment-related and other UC-related complications | All randomised patients, achieved-target population† |
| 7. To assess the effect of treatment(s) on UC-related complications that is mediated through treatment targets | Total treatment effects partitioned into direct and indirect effects | Achieved-target population† |
| 8. To evaluate the change in FC levels from baseline | Change in FC levels from baseline to all follow-up visits | All randomised patients, achieved-target population† |
| 9. To evaluate the change in CRP concentrations from baseline | Change in CRP concentrations from baseline to all follow-up visits | All randomised patients, achieved-target population† |
| 10. To evaluate the change in UC-100 score from baseline | Change in UC-100 score from baseline to weeks 16, 32, 48 and 96 | All randomised patients, achieved-target population† |
| 11. To evaluate changes in HRQoL from baseline | Change in IBDQ from baseline to all follow-up visits | All randomised patients, achieved-target population† |
| 12. To evaluate changes in the WPAI-UC questionnaire from baseline | Change in the WPAI-UC questionnaire from baseline to all follow-up visits | All randomised patients, achieved-target population† |
| 13. To evaluate changes in MCS including the MES and other subcomponents from baseline | Change in MCS, MES and other MCS subcomponents from baseline to weeks 16, 32, 48 and 96 | All randomised patients, achieved-target population† |
| 14. To describe changes in the Geboes score from baseline | Change in Geboes score from baseline to weeks 16, 32, 48 and 96 | All randomised patients, achieved-target population† |
| 15. To describe changes in the RHI score from baseline | Change in RHI score from baseline to weeks 16, 32, 48 and 96 | All randomised patients, achieved-target population† |
| 16. To describe changes in the Nancy Histological Index from baseline | Change in Nancy Histological Index score from baseline to weeks 16, 32, 48 and 96 | All randomised patients, achieved-target population† |
| 17. To evaluate the number of AEs and SAEs among the three randomised groups | AE and SAE counts | All randomised patients |
| 18. To explore urine, stool, colonic mucosa and serum samples for biomarkers and drug concentrations that are associated with clinically important outcomes | Change in biomarkers and drug concentrations from baseline to all time points; association between biomarkers and drug concentrations | All randomised patients |
| 19. To validate the SIQ-UC tool in English-fluent patients | Correlations with the SIQ-UC for the IBDQ, WPAI-UC, PGIS and PGIC; the ability of the SIQ-UC to distinguish between patients by PGIS and PGIC disease severity | All randomised patients |
*Defined as any of the following: (1) hospitalisation for treatment of a UC flare; (2) a colectomy for UC (defined as a colectomy for chronic active or acute severe colitis, but not primarily for dysplasia); (3) rescue therapy (such as new initiation or dose intensification of a corticosteroid, TNFα antagonist, vedolizumab, tofacitinib or ustekinumab) for a documented UC flare; (4) a UC treatment-related complication or (5) other disease-related complication.
†Defined as all randomised patients who achieved their assigned treatment target.
‡Time will be censored for patients who do not achieve their assigned target by week 48.
AE, adverse event; CRP, C reactive protein; EOS, end of study; FC, faecal calprotectin; HRQoL, health-related quality of life; IBDQ, Inflammatory Bowel Disease Questionnaire; MCS, Mayo Clinic Score; MES, Mayo Endoscopic Score; PGIC, Patient Global Impression of Change; PGIS, Patient Global Impression of Severity; RHI, Robarts Histopathology Index; SAE, serious adverse event; SAP, statistical analysis plan; SIQ-UC, Symptoms and Impacts Questionnaire for UC; TNF, tumour necrosis factor; UC, ulcerative colitis; VERDICT, actiVE ulcerative colitis, a RanDomIsed Controlled Trial; WPAI-UC, Work Productivity and Activity Impairment Questionnaire: Ulcerative Colitis.