Purpura, Thrombotic ThrombocytopenicPhase 3PLEX-RCTNCT01433003
The Plasma Large-Volume Exchange RCT
A Phase 3 study testing Plasma Exchange in people with Purpura, Thrombotic Thrombocytopenic and Hemolytic Uremic Syndrome, run by London Health Sciences Centre at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Purpura, Thrombotic Thrombocytopenic, Hemolytic Uremic Syndrome
- What is being tested?
- Plasma Exchange
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteCanada
- Study dates
- Apr 2012to Mar 2015
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Plasma Large-Volume Exchange Randomized Controlled Trial (PLEX-RCT)
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.
Read the 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.
- Being tested
- Plasma Exchange
- Keywords
- Thrombotic thrombocytopenia purpura, hemolytic uremic syndrome, plasma exchange, Improve treatment response, TTP/HUS
- Medical subject headings
- Purpura, Thrombotic Thrombocytopenic, Hemolytic-Uremic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Plasma ExchangeProcedure or surgery
Plasma exchange is a blood purification technique that removes plasma from the blood and replaces it with donor plasma.
| Study group | Role | What they receive |
|---|---|---|
| Standard-dose plasma exchange | Active comparator | 50-75 ml/kg/day Receives: Procedure: Plasma Exchange |
| High-dose Plasma Exchange | Experimental | 125 ml/kg/day up to 10 L/day Receives: Procedure: Plasma Exchange |
What is being measured
The primary outcome is the main question the study is designed to answer.
treatment failure at day 5 and/or 2) non-response or death at 2 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
Measured: baseline to two weeks
Secondary outcomes (1)
All-cause mortality
all-cause mortality at 1-month and 6-months after treatment initiation
Measured: 1 month; 6 months,
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2011 (estimated)
- Study startApr 2012
- Primary completionDec 2014 (estimated)
- Study completionMar 2015 (estimated)
Why it stopped: Funding not obtained
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Purpura, Thrombotic ThrombocytopenicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- London Health Sciences Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr William F Clark, London Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01433003
- Sponsor's protocol ID
- 259509
- Acronym
- PLEX-RCT
- Status last verified
- Apr 2013
- First submitted
- 9 Sep 2011
- Last updated
- 17 Apr 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Plasma Large-Volume Exchange Randomized Controlled Trial (PLEX-RCT)
- ClinicalTrials.gov ID
- NCT01433003
- Acronym / sponsor ID
- PLEX-RCT / 259509
- Keywords
- Thrombotic thrombocytopenia purpura, hemolytic uremic syndrome, plasma exchange, Improve treatment response, TTP/HUS
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Funding not obtained
- Enrolment
- 0 participants (actual)
- Lead sponsor
- London Health Sciences CentreUniversity, hospital or other
- Study start
- Apr 2012
- Primary completion
- Dec 2014 (estimated)
- Study completion
- Mar 2015 (estimated)
- First posted
- 13 Sep 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard-dose plasma exchange | Active comparator | Procedure: Plasma Exchange50-75 ml/kg/day |
| High-dose Plasma Exchange | Experimental | Procedure: Plasma Exchange125 ml/kg/day up to 10 L/day |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age > 18 year-old
- First presentation of TTP/HUS
- Meet all of the following diagnostic criteria:
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Plasma ExchangePlasma exchange is a blood purification technique that removes plasma from the blood and replaces it with donor plasma. | Procedure or surgery | High-dose Plasma Exchange, Standard-dose plasma exchange |
Primary outcome
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
1 secondary outcome
All-cause mortality
Time frame: 1 month; 6 months,
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2013.
Related trials for Purpura, Thrombotic Thrombocytopenic
Not yet recruitingObservational study
Study of Thyroid Dysfunction in Immune Thrombocytopenic Purpura Patients
Thyroid Dysfunction, Immune Thrombocytopenic Purpura
Not yet recruitingPhase 1
Phase 1 Dose Escalation Study of RXIM002 in Autoimmune Cytopenias
Immune Thrombocytopenia (ITP)
RecruitingPhase 2
A Study to Assess the Tolerability of Ianalumab (VAY736) With Investigator's Choice Thrombopoietin Receptor Agonist (IC TPO-RA) in Patients With Primary Immune Thrombocytopenia (ITP)
Primary Immune Thrombocytopenia (ITP), Primary Evans Syndrome (ES)
RecruitingPhase 3
A Study Investigating Intravenous Human Normal Immunoglobulin 10% in Adults With Chronic Immune Thrombocytopenia (ITP)
Chronic Primary Immune Thrombocytopenia (ITP)
RecruitingPhase 1/2
Safety and Preliminary Efficacy of CTX112 in Adult Participants With Relapsed/Refractory Hematologic Autoimmune Disease
Warm Autoimmune Hemolytic Anemia (WAIHA), ITP - Immune Thrombocytopenia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Plasma Exchange in people with Purpura, Thrombotic Thrombocytopenic and Hemolytic Uremic Syndrome, run by London Health Sciences Centre at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 17 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
treatment failure at day 5 and/or 2) non-response or death at 2 weeks (time frame: baseline to two weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2013.