Ignite Creation Date:
2025-12-24 @ 7:14 PM
Ignite Modification Date:
2026-02-23 @ 2:21 AM
Study NCT ID:
NCT01433003
Status:
WITHDRAWN
Last Update Posted:
2013-04-17
First Post:
2011-09-09
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
The Plasma Large-Volume Exchange RCT
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D011697', 'term': 'Purpura, Thrombotic Thrombocytopenic'}, {'id': 'D006463', 'term': 'Hemolytic-Uremic Syndrome'}], 'ancestors': [{'id': 'D011696', 'term': 'Purpura, Thrombocytopenic'}, {'id': 'D011693', 'term': 'Purpura'}, {'id': 'D001778', 'term': 'Blood Coagulation Disorders'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D057049', 'term': 'Thrombotic Microangiopathies'}, {'id': 'D013921', 'term': 'Thrombocytopenia'}, {'id': 'D001791', 'term': 'Blood Platelet Disorders'}, {'id': 'D000095542', 'term': 'Cytopenia'}, {'id': 'D019851', 'term': 'Thrombophilia'}, {'id': 'D006470', 'term': 'Hemorrhage'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D012877', 'term': 'Skin Manifestations'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D014511', 'term': 'Uremia'}, {'id': 'D007674', 'term': 'Kidney Diseases'}, {'id': 'D014570', 'term': 'Urologic Diseases'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}, {'id': 'D000743', 'term': 'Anemia, Hemolytic'}, {'id': 'D000740', 'term': 'Anemia'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D010951', 'term': 'Plasma Exchange'}], 'ancestors': [{'id': 'D001803', 'term': 'Blood Transfusion'}, {'id': 'D001691', 'term': 'Biological Therapy'}, {'id': 'D013812', 'term': 'Therapeutics'}, {'id': 'D010956', 'term': 'Plasmapheresis'}, {'id': 'D001781', 'term': 'Blood Component Removal'}, {'id': 'D016060', 'term': 'Sorption Detoxification'}, {'id': 'D005112', 'term': 'Extracorporeal Circulation'}, {'id': 'D013514', 'term': 'Surgical Procedures, Operative'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 0}}, 'statusModule': {'whyStopped': 'Funding not obtained', 'overallStatus': 'WITHDRAWN', 'startDateStruct': {'date': '2012-04'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2013-04', 'completionDateStruct': {'date': '2015-03', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2013-04-16', 'studyFirstSubmitDate': '2011-09-09', 'studyFirstSubmitQcDate': '2011-09-12', 'lastUpdatePostDateStruct': {'date': '2013-04-17', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2011-09-13', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2014-12', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'treatment failure at day 5 and/or 2) non-response or death at 2 weeks', 'timeFrame': 'baseline to two weeks', 'description': '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'}], 'secondaryOutcomes': [{'measure': 'All-cause mortality', 'timeFrame': '1 month; 6 months,', 'description': 'all-cause mortality at 1-month and 6-months after treatment initiation'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Thrombotic thrombocytopenia purpura', 'hemolytic uremic syndrome', 'plasma exchange', 'Improve treatment response', 'TTP/HUS'], 'conditions': ['Purpura, Thrombotic Thrombocytopenic', 'Hemolytic Uremic Syndrome']}, 'descriptionModule': {'briefSummary': "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.", 'detailedDescription': '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.\n\nHypothesis: 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.\n\nMethods: 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.\n\nResearch 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).\n\nTimeline 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.\n\nFuture 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.\n\nImplications: This study has the potential to be the first major advancement in treating TTP/HUS in twenty years.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Age \\> 18 year-old\n2. First presentation of TTP/HUS\n3. Meet all of the following diagnostic criteria:\n\n * Platelet count \\< 150 x 109 /L\n * Microangiopathic haemolytic anaemia (blood film with presence of red blood cell fragmentation)\n * LDH \\> 1.25 X the upper limits of normal\n * No alternative diagnosis\n\nExclusion Criteria:\n\n1. Secondary TTP/HUS\n2. Relapsing TTP/HUS\n3. Hypersensitivity to blood product\n4. Patient has received 2 or more plasma exchange treatment since symptom started over the last 1 week\n5. Received medication, including cyclosporine, cyclophosphamide, rituximab for treatment of TTP/HUS\n6. Other causes of thrombocytopenia than TTP/HUS'}, 'identificationModule': {'nctId': 'NCT01433003', 'acronym': 'PLEX-RCT', 'briefTitle': 'The Plasma Large-Volume Exchange RCT', 'organization': {'class': 'OTHER', 'fullName': 'London Health Sciences Centre'}, 'officialTitle': 'The Plasma Large-Volume Exchange Randomized Controlled Trial (PLEX-RCT)', 'orgStudyIdInfo': {'id': '259509'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Standard-dose plasma exchange', 'description': '50-75 ml/kg/day', 'interventionNames': ['Procedure: Plasma Exchange']}, {'type': 'EXPERIMENTAL', 'label': 'High-dose Plasma Exchange', 'description': '125 ml/kg/day up to 10 L/day', 'interventionNames': ['Procedure: Plasma Exchange']}], 'interventions': [{'name': 'Plasma Exchange', 'type': 'PROCEDURE', 'description': 'Plasma exchange is a blood purification technique that removes plasma from the blood and replaces it with donor plasma.', 'armGroupLabels': ['High-dose Plasma Exchange', 'Standard-dose plasma exchange']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'N6A 4G5', 'city': 'London', 'state': 'Ontario', 'country': 'Canada', 'facility': 'Central Facility', 'geoPoint': {'lat': 42.98339, 'lon': -81.23304}}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'London Health Sciences Centre', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor', 'investigatorFullName': 'Dr William F Clark', 'investigatorAffiliation': 'London Health Sciences Centre'}}}}