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Review
. 2024 Dec;60(11-12):1512-1524.
doi: 10.1111/apt.18326. Epub 2024 Oct 15.

Clinical Trial Design Considerations for Hospitalised Patients With Ulcerative Colitis Flares and Application to Study Hyperbaric Oxygen Therapy in the NIDDK HBOT-UC Consortium

Parambir S Dulai  1 , Lauren Balmert Bonner  2   3 , Charlotte Sadler  4 , Laura E Raffals  5 , Gursimran Kochhar  6 , Peter Lindholm  4 , Jay C Buckey Jr  7 , Gary N Toups  8 , Libeth Rosas  1 , Neeraj Narula  9 , Vipul Jairath  10   11   12 , Sailish Honap  13   14 , Laurent Peyrin-Biroulet  14 , Bruce E Sands  15 , Stephen B Hanauer  1 , Denise M Scholtens  2   3 , Corey A Siegel  16 ; HBOT‐UC Consortium Investigators
Collaborators, Affiliations
Review

Clinical Trial Design Considerations for Hospitalised Patients With Ulcerative Colitis Flares and Application to Study Hyperbaric Oxygen Therapy in the NIDDK HBOT-UC Consortium

Parambir S Dulai et al. Aliment Pharmacol Ther. 2024 Dec.

Abstract

Background: Patients with ulcerative colitis (UC) who are hospitalised for acute severe flares represent a high-risk orphan population.

Aim: To provide guidance for clinical trial design methodology in these patients.

Methods: We created a multi-centre consortium to design and conduct a clinical trial for a novel therapeutic intervention (hyperbaric oxygen therapy) in patients with UC hospitalised for moderate-severe flares. During planning, we identified and addressed specific gaps for inclusion/exclusion criteria; disease activity measures; pragmatic trial design considerations within care pathways for hospitalised patients; standardisation of care delivery; primary and secondary outcomes; and sample size and statistical analysis approaches.

Results: The Truelove-Witt criteria should not be used in isolation. Endoscopy is critical for defining eligible populations. Patient-reported outcomes should include rectal bleeding and stool frequency, with secondary measurement of urgency and nocturnal bowel movements. Trial design needs to be tailored to care pathways, with early intervention focused on replacing and/or optimising responsiveness to steroids and later interventions focused on testing novel rescue agents or strategies. The PRECIS-2 framework offers a means of tailoring to local populations. We provide standardisation of baseline testing, venous thromboprophylaxis, steroid dosing, discharge criteria and post-discharge follow-up to avoid confounding by usual care variability. Statistical considerations are provided given the small clinical trial nature of this population.

Conclusion: We provide an outline for framework decisions made for the hyperbaric oxygen trial in patients hospitalised for UC flares. Future research should focus on the remaining gaps identified.

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Figures

FIGURE 1
FIGURE 1
Usual care pathway for hospitalised ulcerative colitis patients and considerations for trial designs. The usual care pathway for hospitalised UC patients was first defined to allow for determination of how different PRECIS‐2 domains would need to be addressed to optimise trial design while maintaining a pragmatic approach.
FIGURE 2
FIGURE 2
PRECIS‐2 domains, gaps identified in each domain for hospitalised ulcerative colitis trials, and decisions made to design a pragmatic trial for hyperbaric oxygen therapy. PRECIS‐2 domains are outlined, barriers to each domain identified and decisions made or actions taken to overcome those barriers. A score of 5 (outer circle) represents a very pragmatic choice for this domain, a score of 1 (inner circle) represents a very explanatory choice for this domain and a score of 3 represents an equally pragmatic/explanatory choice for this domain. AI, artificial intelligence; BMs, bowel movements; IV, intravenous; PRO, patient‐reported outcome.
See this image and copyright information in PMC

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