None listed
Conditions
Brief summary
Ulcerative colitis (UC) is an immune mediated disease that causes sores in the large bowel and symptoms such as diarrhoea, passage of blood and abdominal pain. Acute severe ulcerative colitis (ASUC) is the most severe form of this condition, which requires admission to the hospital for treatment with intravenous steroids as their first line of treatment. In this randomised open label trial, we will aim to explore whether the addition of Upadacitinib, a medication belonging to family of drugs known as janus kinase (JAK) inhibitors, to intravenous steroids is effective, feasible and safe. The primary aims of this pilot study are to determine if, in patients admitted to hospital with ASUC, upadacitinib in addition to steroids is more effective than steroid treatment alone in inducing clinical response and reducing the need for rescue therapy by Day 5 of admission, and whether this strategy is feasible, and safe. The secondary aims include evaluation of efficacy of upadacitinib in improving symptomatic and biochemical response at day 5; likelihood of colectomy during index hospitalisation; cost and duration of index hospitalisation. We hypothesise that upadacitinib in addition to corticosteroids will be more effective that corticosteroid treatment alone in inducing response and reduce need for rescue therapy, and will be a feasible and safe strategy.
Interventions
Upadacitinib 45mg tablet orally once daily for the first 5 days of admission. This intervention will be in addition to standard of care treatment with intravenous hydrocortisone, which will be administered at a dose of 100mg 4 times daily. The clinical trial team will administer the trial medication daily for the duration of the study, and adherence will be monitoring daily using electronic medication record.
Sponsors
The University of Melbourne
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
a). Aged between 18 to 65 b) Have ability to give written informed consent; c) Have confirmed ASUC defined by the modified Truelove and Witts criteria; d) Being admitted for management with intravenous corticosteroids; e) Laboratory assessments at screening within the following parameters: a. Haemoglobin greater than or equal to 80 g/L b. Absolute neutrophil count greater than or equal to 1.5 x 10^3/µL c. Absolute lymphocyte count greater than or equal to 0.5 x 10^3/µL d. Platelets greater than or equal to 100 x 10^3/µL e. Aspartate aminotransferase and alanine aminotransferase less than or equal to 2 x upper limit of normal (ULN) f. Total bilirubin less than or equal to 2 x ULN g. Alkaline phosphatase less than 3 x ULN h. Estimated glomerular filtration rate greater than 60 mL/min
Exclusion criteria
a) Evidence of fulminant UC (toxic megacolon as evidenced by transverse colon diameter greater than or equal to 60mm and one of: fever [T greater than or equal to 37.80C], tachycardia [pulse rate greater than or equal to 90 beats per minute]); b) Pregnant or breastfeeding; c) Women of reproductive potential unless using effective contraception during treatment and for 4 weeks following the final dose of upadacitinib. d) Evidence of infection on clinical evaluation; e) History of solid organ or haematological malignancy, significant cardiorespiratory disease, severe hepatic impairment, thrombophilia or thromboembolic disorder; f) Any absolute contraindication to steroids; g) History of ischaemic colitis, radiation colitis, ileoanal pouch; h) History of ileostomy or colostomy; i) History of HIV, hepatitis B, hepatitis C, or active or latent tuberculosis; j) History of symptomatic herpes zoster within 16 weeks of randomization, or any history of disseminated herpes simplex, disseminated herpes zoster, ophthalmic zoster, or varicella zoster virus central nervous system infections; k) History of faecal microbiota transplantation within 2 weeks of presentation; l) Inability to take oral medications; m) Concomitant treatment with strong CYP3A4 inhibitors or inducers; n) Patients who have received live or attenuated vaccines within 28 days; o) Be part of any other interventional trial; p) Any unstable or chronic medical condition, including, but not limited to, cardiac, pulmonary, hepatic (e.g., cirrhosis), or psychiatric problem (including alcohol or drug abuse) that, in the opinion of the investigator, would make the participant unsuitable for the study or would prevent compliance with the study protocol
Outcome results
None listed