CONCISE COlchicine iN Circulating Inflammatory markers after StrokE
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- The primary endpoint is the difference in mean or median change in inflammatory biomarker panel from baseline to end of treatment
研究概览
简要总结
Vascular inflammation drives risk of recurrent stroke, cardiac and vascular events in patients with atheroma and atherosclerosis. Anti inflammatory therapies, such as colchicine, can reduce the risk of further events but little is known whether colchicine also lowers serum biomarkers of inflammation.
Patients with a history of stroke or TIA and evidence of atherosclerosis at any site, defined as any of: • intra-cranial or extra-cranial atheroma causing >30% stenosis or occlusion ipsilateral to the infarct • Any atheroma proximal to the infarct in patients with cryptogenic stroke/ESUS in whom an alternative mechanism if not felt to be more likely in the opinion of the investigator • Patient has a history of ischemic heart disease (IHD) or peripheral vascular disease (PVD), or has undergone revascularisation procedures for IHD or PVD. and raised hsCRP ³2mg/L on baseline blood tests will be eligible for inclusion. Patients will be prescribed pleotropicanti-inflammatory colchicine 0.5mg daily for 30 days. A panel of blood biomarkers will be drawn pre and post treatment.
The primary outcome will be calculated % change in hsCRP , IL-6 and other blood biomarkers of inflammation comparing before treatment with after treatment.
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Paired Cohort Study
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Prior ischaemic stroke or ischaemic attack.
- •Living at home and independent (walking without the aid of another person, but may have some help for daily activities) without cognitive impairment causing limitation of daily function.
- •Medically-stable, and capable of participating in a research study and likely to follow study procedures, in the opinion of the study physician
- •Willing to provide informed consent
- •Age >18 years and <90 years
- •No history of chronic kidney disease and eGFR>50ml/min measured during screening phase
- •Serum hsCRP³2mg/L measured within 6 months of study entry
- •History of ischaemic stroke or TIA defined as a. Cerebral, spinal cord or retinal ischaemia based on neuropathological or neuroimaging evidence or clinical evidence of permanent injury. TIA= neurological dysfunction caused by focal cerebral or retinal ischaemia with clinical symptoms lasting <24 hours.
- •Presence of atheroma defined as: - intra-cranial or extra-cranial atheroma causing >30% stenosis or occlusion ipsilateral to the infarct AND/OR - Any atheroma proximal to the infarct in patients with cryptogenic stroke/ESUS in whom an alternative mechanism if not felt to be more likely in the opinion of the investigator AND/OR - Patient has a history of ischemic heart disease (IHD) or peripheral arterial disease (PAD), or has undergone revascularisation procedures for IHD or PAD.
排除标准
- •Stroke or TIA likely caused by identified atrial fibrillation (permanent or paroxysmal)
- •Requirement for colchicine therapy for acute gout or gout prevention or other rheumatological disorder.
- •Known sensitivity or allergy to colchicine.
- •Active malignancy or known Hepatitis B, C or HIV infection.
- •Dementia or cognitive impairment sufficient to impair independence in basic activities of daily living.
- •Women of childbearing potential. (Must be >24 months free of menstrual periods)
- •Patient concurrently enrolled in CONVINCE trial.
- •Stroke or TIA caused by other identified cardiac source (intracardiac thrombus, endocarditis, metallic heart value, low ejection fraction <30%)
- •History of myalgia with raised CK on statin therapy
- •Blood dyscrasia (Hb <10g/dl, Plt <150x1o^9/L, WCC <4x10^9/L) or other history of blood dyscrasia requiring follow up with haematology.
- •Impaired hepatic function (transaminases >twice ULN)
- •Concurrent treatment with contra-indicated drugs: CYP3A4 inhibitors (clarithromycin, erythromycin, telithromycin, macrolides, ketoconazole, itraconazole, voriconazole, tolbutamide, ritonavir, atazanavir, indinavir, other HIV protease inhibitors, verapamil, diltiazem, quinidine, digoxin, disulfiram) or P-gp inhibitors (cyclosporine) at screening.
- •Symptomatic peripheral neuropathy or progressive neuromuscular disease
- •Pre-existing inflammatory bowel disease, Crohn’s disease, Ulcerative colitis or chronic diarrhoea
- •Pre-existing inflammatory condition, intercurrent infection or other indication for regular anti-inflammatory therapies e.g., steroid, NSAIDs, immunosuppressants.
结局指标
主要结局
The primary endpoint is the difference in mean or median change in inflammatory biomarker panel from baseline to end of treatment
The primary endpoint is the difference in mean or median change in inflammatory biomarker panel from baseline to end of treatment
次要结局
- The secondary endpoint is the proportion of patients at the end of treatment whose hsCRP level is suppressed below 2mg/L. Description of changes in inflammatory markers after treatment will also be a secondary analysis. Secondary endpoints will also include proportion of patients who discontinue colchicine treatment due to poor tolerability and prevalence of adverse events associated with colchicine treatment.
研究者
Prof Peter Kelly
Scientific
University College Dublin