The Plasma Large-Volume Exchange RCT

NCT01433003 | Withdrawn Phase 3 DMC

• 1 other identifier: 259509
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Purpura, Thrombotic Thrombocytopenic; Hemolytic Uremic Syndrome

Keywords

Thrombotic thrombocytopenia purpura; hemolytic uremic syndrome; plasma exchange; Improve treatment response; TTP/HUS

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• All-cause mortality

  1 month; 6 months,

Study Arms (2)

Standard-dose plasma exchange

ACTIVE COMPARATOR

50-75 ml/kg/day

Procedure: Plasma Exchange

High-dose Plasma Exchange

EXPERIMENTAL

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

Procedure: Plasma Exchange

Interventions

Plasma Exchange PROCEDURE

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

High-dose Plasma Exchange; Standard-dose plasma exchange

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• London Health Sciences Centre: lead

Study Sites (1)

Central Facility

London, Ontario, N6A 4G5, Canada

Location

MeSH Terms

Conditions

Purpura, Thrombotic Thrombocytopenic; Hemolytic-Uremic Syndrome

Interventions

Plasma Exchange

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Thrombophilia; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms; Uremia; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Anemia, Hemolytic; Anemia

Intervention Hierarchy (Ancestors)

Blood Transfusion; Biological Therapy; Therapeutics; Plasmapheresis; Blood Component Removal; Sorption Detoxification; Extracorporeal Circulation; Surgical Procedures, Operative

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 9, 2011
• First Posted: September 13, 2011
• Study Start: April 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: March 1, 2015
• Last Updated: April 17, 2013

Record last verified: 2013-04

Locations

CA (1)