Efficacy and safety of addition of Low-dose Colchicine in Takayasu arteritis with persistent systemic inflammation: a multi-institutional Randomized controlled trial
试验速览
- 阶段
- 2/3 期
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 7
- 主要终点
- The percentage of participants who attain complete remission at 24 weeks defined as by attainment of ITAS score of 0 with CRP less than 10mg per litre AND stable angiogram with steroid dose less than or equal to 2.5mg per day at 24 weeks.
研究概览
简要总结
Objectives: The primary objective is to study the efficacy of 24 weeks of add on colchicine as compared with conventional therapy in TAK with persistent systemic inflammation.
Secondary objective is i) To assess and compare changes in serum biomarkers and whole-blood-transcriptomics before and after 24 weeks of therapy with the trial drugs.
Methods: Patients with TAK with persistently raised CRP>10mg/L, with ITAS<2 (Figure-2) would be recruited from multiple tertiary-care centres and randomly assigned (1:1) to receive either add-on-colchicine or conventional therapy. All patients would undergo 3-monthly clinical and CRP assessment and angiogram, biomarker profiling by multiplex-ELISA and RNA sequencing at 24 weeks. RNA-sequencing will be also performed for TAK patients with normal CRP as disease controls. Primary outcome is defined as percentage of patients achieving complete remission at 24 weeks with steroids≤2.5mg/day. Serum biomarker concentration and expression of selected genes which are differentially gene expressed between trial patients will be compared before and after 24 weeks of therapy with study drugs.
Expected outcomes: Colchicine may be better than conventional therapy as add-on agent in inducing remission, reverting molecular aberrations in TAK with persistent systemic inflammation. The specific molecular pathways driving the effect of colchicine on persistent systemic inflammation in TAK will be identified.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Outcome Assessor Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 60.00 Year(s)（—）
- 性别
- All
入选标准
- •1.TAK with persistent systemic inflammation defined as having least 2 consecutive values of CRP more than or equal to 10mg per litre over a minimum of 6 months, without any alternative explanation of raised inflammatory markers 2.On stable immunosuppressants with steroids less than 7.5mg per day during at least 1 month prior to enrolment.
- •3.Age between 18 to 60 years of age 4.Mild or no clinical activity as defined by Indian Takayasu arteritis 2010 score ie ITAS more than or equal to 2 and ITAS score of 0 respectively.
- •5.Have signed the written informed consent.
排除标准
- •1.Diastolic blood pressure above 90mm Hg in upper limbs or above 100mm Hg in lower limbs despite 3 antihypertensives.
- •2.Serum creatinine of more than 1.7mg / dl or eGFR of less than 50 ml/min/ 1.73m
- •3.Presence of heart failure or left ventricular ejection fraction of less than 45%.
- •5.Requiring planned vascular intervention in the next 24 months.
- •6.Ischemic stroke in the preceding 3 months 7.Presence of severe Aortic regurgitation.
- •8.Presence of inflammatory bowel disease or severe abdominal pain.
- •9.Pregnancy or planning pregnancy or breast feeding during next 12 months.
结局指标
主要结局
The percentage of participants who attain complete remission at 24 weeks defined as by attainment of ITAS score of 0 with CRP less than 10mg per litre AND stable angiogram with steroid dose less than or equal to 2.5mg per day at 24 weeks.
时间窗: 24 weeks
次要结局
未报告次要终点
研究者
Ruchika Goel
Christian Medical College, Vellore