- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01433003
The Plasma Large-Volume Exchange RCT (PLEX-RCT)
The Plasma Large-Volume Exchange Randomized Controlled Trial (PLEX-RCT)
Study Overview
Status
Intervention / Treatment
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 Type
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
Ontario
-
London, Ontario, Canada, N6A 4G5
- Central Facility
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: Standard-dose plasma exchange
50-75 ml/kg/day
|
Plasma exchange is a blood purification technique that removes plasma from the blood and replaces it with donor plasma.
|
EXPERIMENTAL: High-dose Plasma Exchange
125 ml/kg/day up to 10 L/day
|
Plasma exchange is a blood purification technique that removes plasma from the blood and replaces it with donor plasma.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
treatment failure at day 5 and/or 2) non-response or death at 2 weeks
Time Frame: 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
|
baseline to two weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
All-cause mortality
Time Frame: 1 month; 6 months,
|
all-cause mortality at 1-month and 6-months after treatment initiation
|
1 month; 6 months,
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Kidney Diseases
- Urologic Diseases
- Hematologic Diseases
- Hemorrhage
- Anemia
- Blood Coagulation Disorders
- Skin Manifestations
- Thrombocytopenia
- Blood Platelet Disorders
- Thrombophilia
- Anemia, Hemolytic
- Thrombotic Microangiopathies
- Purpura, Thrombocytopenic
- Uremia
- Purpura
- Purpura, Thrombotic Thrombocytopenic
- Hemolysis
- Hemolytic-Uremic Syndrome
Other Study ID Numbers
- 259509
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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