The Plasma Large-Volume Exchange Randomized Controlled Trial (PLEX-RCT)
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 试验地点
- 2
- 主要终点
- treatment failure at day 5 and/or 2) non-response or death at 2 weeks
研究概览
简要总结
Thrombotic thrombocytopenia purpura / hemolytic uremic syndrome (TTP/HUS) is a rare, life-threatening disorder. TTP/HUS causes multiple blood clots to form, which prevents blood from reaching the brain and kidneys. TTP/HUS affects 3-5 people per million per year. Anyone can develop TTP/HUS, but it is most common among 30-40 year olds, and women are twice as likely as men to acquire the condition. TTP/HUS sometimes develops as a result of medication use, pregnancy or cancer; however, for the majority of patients (80%) the cause of TTP/HUS is unknown. In 1991, researchers discovered that plasma exchange was superior to plasma infusion in treating idiopathic TTP/HUS. During plasma exchange the patient's blood plasma is removed and replaced with healthy blood plasma. Without plasma exchange, the survival rate for TTP/HUS is extremely low, with fewer than 5% of patients surviving. Treating TTP/HUS with plasma exchange improved the survival rate to 80%. Although this represents a dramatic improvement, researchers are still searching for methods to improve survival. No major advances in treating TTP/HUS have occurred in the past 20 years. Recent research suggests that high-dose plasma exchange may improve the survival of TTP/HUS patients. The investigators will conduct a randomized controlled trial to test whether treating TTP/HUS patients with high-dose versus standard-dose plasma exchange improves the treatment response. The investigators will recruit 150 patients with TTP/HUS from 9 centres across Canada over three years. The investigators will evaluate whether high-dose plasma exchange improves the treatment response, survival, and whether it reduces the number and volume of plasma exchange procedures and duration of hospital stay.
详细描述
Background: Thrombotic thrombocytopenia purpura / haemolytic uremic syndrome (TTP/HUS) is a rare blood disorder with a high mortality rate of >95% when left untreated. In 1991, researchers discovered that treating TTP/HUS with plasma exchange vs. plasma infusion dramatically improved the survival rate, from 60% to 80%.The optimal plasma dose for treating TTP/HUS is unknown; however, recent research suggests that high-dose plasma exchange may improve survival in patients with TTP/HUS.
Hypothesis: Treatment of TTP/HUS with high-dose vs. standard-dose plasma exchange will significantly decrease the composite outcome of 1) treatment failure at day 5 and/or 2) non-response or death at 2 weeks.
Methods: The investigators will conduct a multi-centre, parallel group randomized controlled trial. The investigators anticipate recruiting 150 eligible patients with idiopathic TTP/HUS from 9 centres across Canada over 2.25 years. Patients will be randomized to receive high-dose plasma exchange (125 ml/kg/day up to 10 L/day plasma volume) or standard-dose plasma exchange (50-75 ml/kg/day; approximately 1-1.5 plasma volume). The primary composite outcome includes treatment failure at day 5 or non-response or death from any cause at 2 weeks. Secondary outcomes include the individual components of the primary outcome, non-response or death from any cause at month 1 and month 6, days to remission, duration of hospital stay, number and volume of plasma exchange treatments, and cost minimization.
Research Team: Our multi-centre team is part of the Canadian Apheresis Group, which was established in 1980 and currently operates in 30 centres across Canada. Collectively, the Canadian Apheresis Group treats 150 TTP/HUS patients each year. Our team includes experienced haematologists, nephrologists, epidemiologists and a biostatistician. The investigators have successfully collaborated on several projects and have an excellent publication record (>50 publications across more than 15 journals including the New England Journal of Medicine).
Timeline and Budget: Because TTP/HUS is a relatively rare disorder (an orphan disease), the investigators will recruit patients over 2.25 years from across Canada to achieve a sufficiently large sample size. A cost minimization study will be carried out in conjunction with the RCT to provide insight into potential costing.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age > 18 year-old
- •First presentation of TTP/HUS
- •Meet all of the following diagnostic criteria:
- •Platelet count < 150 x 109 /L
- •Microangiopathic haemolytic anaemia (blood film with presence of red blood cell fragmentation)
- •LDH > 1.25 X the upper limits of normal
- •No alternative diagnosis
排除标准
- •Secondary TTP/HUS
- •Relapsing TTP/HUS
- •Hypersensitivity to blood product
- •Patient has received 2 or more plasma exchange treatment since symptom started over the last 1 week
- •Received medication, including cyclosporine, cyclophosphamide, rituximab for treatment of TTP/HUS
- •Other causes of thrombocytopenia than TTP/HUS
结局指标
主要结局
treatment failure at day 5 and/or 2) non-response or death at 2 weeks
时间窗: baseline to two weeks
LDH \>1.25 x the upper limit of normal at Day 5 and \<50% decrease from initial value, or Initial platelet count \<50 x 109/L with \<100% rise at Day 5, or Initial platelet count 50-99 x 109/L with \<50% rise at Day 5, or Initial platelet count 100-150 x 109/L with Day 5 \<150x 109/L, or LDH \>1.25 x the upper limit of normal at 2 weeks, or Platelet count \<150 x 109/L at 2 weeks, or Persistent or new neurological symptoms at 2 weeks
次要结局
- All-cause mortality(1 month; 6 months,)
研究者
Dr William F Clark
Professor
London Health Sciences Centre