The Plasma Large-Volume Exchange RCT

NCT ID: NCT01433003

Last Updated: 2013-04-17

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-30
• Study Completion Date: 2015-03-31

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.

Conditions

Purpura, Thrombotic Thrombocytopenic; Hemolytic Uremic Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard-dose plasma exchange

50-75 ml/kg/day

Group Type: ACTIVE_COMPARATOR

Plasma Exchange

Intervention Type: PROCEDURE

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

High-dose Plasma Exchange

125 ml/kg/day up to 10 L/day

Group Type: EXPERIMENTAL

Plasma Exchange

Intervention Type: PROCEDURE

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

Interventions

Plasma Exchange

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

Intervention Type: PROCEDURE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

London Health Sciences Centre

OTHER

Sponsor Role: lead

Responsible Party

Dr William F Clark

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Central Facility

London, Ontario, Canada

Countries

Canada

Other Identifiers

259509

Identifier Type: -

Identifier Source: org_study_id