The Plasma Large-Volume Exchange RCT

Hemolytic Uremic Syndrome Clinical Trial

— PLEX-RCT  

Official title:

The Plasma Large-Volume Exchange Randomized Controlled Trial (PLEX-RCT)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01433003
• Other study ID #: 259509
• Status: Withdrawn
• Phase: Phase 3
• First received: September 9, 2011
• Last updated: April 16, 2013
• Start date: April 2012
• Est. completion date: March 2015

Study information

• Verified date: April 2013
• Source: London Health Sciences Centre
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Canadian Institutes of Health Research
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: March 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hemolytic Uremic Syndrome
• Hemolytic-Uremic Syndrome
• Purpura, Thrombotic Thrombocytopenic

Intervention

Procedure:
• Plasma Exchange
Plasma exchange is a blood purification technique that removes plasma from the blood and replaces it with donor plasma.

Locations

Country	Name	City	State
Canada	Central Facility	London	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
London Health Sciences Centre

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	baseline to two weeks	Yes
Secondary	All-cause mortality	all-cause mortality at 1-month and 6-months after treatment initiation	1 month; 6 months,	Yes