The Plasma Large-Volume Exchange Randomized Controlled Trial (PLEX-RCT)
18 Years
N/A
Both
Purpura, Thrombotic Thrombocytopenic, Hemolytic Uremic Syndrome
Trial Information
The Plasma Large-Volume Exchange Randomized Controlled Trial (PLEX-RCT)
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.
Inclusion Criteria:
1. Age > 18 year-old
2. First presentation of TTP/HUS
3. 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
Exclusion Criteria:
1. Secondary TTP/HUS
2. Relapsing TTP/HUS
3. Hypersensitivity to blood product
4. Patient has received 2 or more plasma exchange treatment since symptom started over
the last 1 week
5. Received medication, including cyclosporine, cyclophosphamide, rituximab for
treatment of TTP/HUS
6. Other causes of thrombocytopenia than TTP/HUS
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
treatment failure at day 5 and/or 2) non-response or death at 2 weeks
Outcome Description:
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
Outcome Time Frame:
baseline to two weeks
Safety Issue:
Yes
Authority:
Canada: Canadian Institutes of Health Research
Study ID:
259509
NCT ID:
NCT01433003
Start Date:
April 2012
Completion Date:
March 2015
Related Keywords:
- Purpura, Thrombotic Thrombocytopenic
- Hemolytic Uremic Syndrome
- Thrombotic thrombocytopenia purpura
- hemolytic uremic syndrome
- plasma exchange
- Improve treatment response
- TTP/HUS
- Hemolytic-Uremic Syndrome
- Purpura
- Purpura, Thrombotic Thrombocytopenic
- Azotemia
- Hemolysis
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