Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-24 @ 7:14 PM
Ignite Modification Date:
2025-12-24 @ 7:14 PM
NCT ID:
NCT01433003
Brief Summary:
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.
Detailed Description:
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.
Future Directions: If the investigators can demonstrate that high-dose plasma exchange significantly improves the primary outcome, the investigators will pursue a multi-national collaboration with American, Chinese and European Centres to investigate other important outcomes including optimal dosing, cost-effectiveness and survival.
Implications: This study has the potential to be the first major advancement in treating TTP/HUS in twenty years.
Study:
NCT01433003
Study Brief:
Protocol Section:
NCT01433003