Tofacitinib Versus Cyclosporine for Steroid Refractory Acute Severe Ulcerative Colitis: An Open Label Randomized Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 96
- 主要终点
- Treatment failure
研究概览
简要总结
This randomised trial plans to compare oral tofacitinib with intravenous cyclosporine in patients with acute severe ulcerative colitis who have failed to respond to intravenous steroids
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients admitted with Acute severe ulcerative colitis as defined by Modified Truelove and Witts Criteria WITH Failure to respond to intravenous steroids (Hydrocortisone 100 mg IV QID OR IV Methylprednisolone 60 mg IV OD) as defined by
- •Day 3 non-response as per Oxford criteria (stool frequency of > 8/day, OR stool frequency between 3-8 with CRP > 45 mg/L PLUS
- •Ongoing activity as defined by Partial Mayo Score of > 3 (rectal bleeding sub-score of >1)
- •Decision to start second line therapy (within 5-7 days of starting intravenous steroids)
排除标准
- •Age <18, Age > 65 years
- •E1 disease (involvement distal to rectosigmoid junction only)
- •Crohn's disease
- •Contraindication to intravenous cyclosporine or oral tofacitinib
- •Renal failure, uncontrolled hypertension, seizure disorder,and uncorrected hypomagnesemia (<1.5 mg/L)
- •Previous thrombosis, or prothrombotic state, on oral contraceptive, history of herpes zoster, active TB, active hepatitis, past opportunistic infections, h/o diverticulitis, Age >50 plus at least one cardiac risk factor
- •Patient wants treatment with intravenous infliximab or wants surgery
- •Underlying sepsis or active infection (Enteric infections, Clostridium difficile, active hepatitis B or C, Tuberculosis, zoster, CMV disease)
- •Toxic megacolon, previous dysplasia or any indication of immediate surgery
- •Known malignancy
- •Pregnancy or Lactation
- •Unwilling to provide consent or for follow-up
研究组 & 干预措施
Group A
Group A: Intravenous Cyclosporine 2 mg/kg continuous infusion for 5-7 days and then shifted to oral cyclosporine 4 mg/kg/day in two divided doses for 12 weeks
干预措施: Cyclosporine (Drug)
Group B
Oral Tofacitinib 10 mg TDS for 3 days, and then 10 mg BD to complete 8 weeks followed by 5 mg BD till follow-up (14 weeks)
干预措施: Tofacitinib (Drug)
结局指标
主要结局
Treatment failure
时间窗: 14 weeks
I) At Day 7 Absence of clinical response at day 7 (as defined by Partial Mayo of \> 3) II) By Day 98 1. Relapse (Partial Mayo Score of 3 or more) between day 7 and day 98 requiring additional therapy 2. Absence of steroid free remission at 14 weeks (Mayo \< 2 with MES 1 or less) 3. Need for colectomy, third line medical rescue or biologics or mortality 4. Serious adverse effect needing interruption of treatment
次要结局
- Endoscopic healing(Day 98)
- Clinical response(7 days)
- Absence of steroid free remission(day 98)
- Colectomy free survival(98 days)
- Time to clinical response(98 days)
- Serious adverse effects(98 days)
研究者
Vishal Sharma
Associate Professor
Post Graduate Institute of Medical Education and Research, Chandigarh