Plasma Exchange and Glucocorticoids for Treatment of Anti-Neutrophil Cytoplasm Antibody (ANCA) - Associated Vasculitis
- Conditions
- Microscopic Polyangiitis (MPA)Granulomatosis With Polyangiitis (Wegener's) (GPA)
- Interventions
- Procedure: Plasma ExchangeOther: No Plasma ExchangeDrug: Glucocorticoids [Standard Dose]Drug: Glucocorticoids [Reduced Dose]
- Registration Number
- NCT00987389
- Lead Sponsor
- University of Pennsylvania
- Brief Summary
The purpose of this study is to determine whether plasma exchange as well as immunosuppressive therapy are effective in reducing death and end-stage renal disease (ESRD). The trial will also study whether a reduced cumulative dosing regimen of glucocorticoids is as effective as a standard disease regimen.
The FDA-OOPD is one of the funding sources for this study.
- Detailed Description
Granulomatosis with polyangiitis (Wegener's) (WG) and microscopic polyangiitis (MPA) are syndromes of primary systemic vasculitis associated with anti-neutrophil cytoplasm antibodies (ANCA). Together, these syndromes are grouped as ANCA-associated systemic vasculitis (AAV).
Plasma exchange, a method of rapidly removing potentially pathogenic ANCA and other mediators of inflammation and coagulation, has shown promise as an adjunctive therapy in AAV to improve early disease control and improve rates of renal recovery in severe disease. Glucocorticoids (steroids) are a standard of care in the treatment of AAV. High doses of glucocorticoids early in disease, although reduce disease activity due to their anti-inflammatory and immunosuppressive properties, also increase the risk of infection, particularly in the elderly and in the presence of uremia. There is no randomized trial data to guide glucocorticoids dosing.
Patients with severe new or relapsing AAV and pulmonary hemorrhage and/or renal disease will be eligible for this trial.
Subjects participating in this study will be randomized to receive one of the following groups;
1. Plasma exchange - 7 exchanges and, either standard or low-dose glucocorticoids or
2. No plasma exchange and, either standard or low-dose glucocorticoids
All studies will receive standard remission-induction therapy with either cyclophosphamide or rituximab.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 704
• New or previous clinical diagnosis of granulomatosis with polyangiitis or microscopic polyangiitis consistent with the Chapel-Hill consensus definitions
AND
• Positive test for proteinase 3-ANCA or myeloperoxidase-ANCA
AND
-
Severe vasculitis defined by at least one of the following:
-
Renal involvement characterized by both of the following:
- Renal biopsy demonstrating focal necrotizing glomerulonephritis or active urine sediment characterized by glomerular haematuria or red cell casts and proteinuria
AND
- eGFR <50 ml/min/1.73 m2
-
Pulmonary hemorrhage due to active vasculitis defined by:
- A compatible chest x-ray or CT scan (diffuse pulmonary infiltrates)
AND
- The absence of an alternative explanation for all pulmonary infiltrates (e.g. volume overload or pulmonary infection)
AND
-
At least one of the following:
- Evidence of alveolar hemorrhage on bronchoscopic examination or increasingly bloody returns with bronchoalveolar lavage
- Observed hemoptysis
- Unexplained anemia (<10 g/dL) or documented drop in hemoglobin >1 g/dL)
- Increased diffusing capacity of carbon dioxide
-
-
Provision of informed consent by patient or a surrogate decision maker
- A diagnosis of vasculitis other than granulomatosis with polyangiitis or microscopic polyangiitis
- Positive serum anti-glomerular basement membrane antibody test or renal biopsy demonstrating linear glomerular immunoglobulin deposition
- Receipt of dialysis for >21 days immediately prior to randomization or prior renal transplant
- Age <15 years
- Pregnancy at time of study entry
- Treatment with >1 IV dose of cyclophosphamide and/or >14 days of oral cyclophosphamide and/or >14 days of prednisone/prednisolone (>30 mg/day) and/or >1 dose of rituximab within the 28 days immediately prior to randomization
- A comorbidity that, in the opinion of the investigator, precludes the use of cyclophosphamide, glucocorticoids, or plasma exchange or absolutely mandates the use of plasma exchange
- Plasma exchange in 3 months prior to randomization
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Plasma Exchange with Standard Glucocorticoids Plasma Exchange Participants in this arm undergo plasma exchange and take a standard glucocorticoid dose. Plasma Exchange with Standard Glucocorticoids Glucocorticoids [Standard Dose] Participants in this arm undergo plasma exchange and take a standard glucocorticoid dose. Plasma Exchange with Reduced-Dose Glucocorticoids Glucocorticoids [Reduced Dose] Participants in this arm undergo plasma exchange and take a reduced glucocorticoid dose. No Plasma Exchange with Standard Glucocorticoids No Plasma Exchange Participants in this arm do not undergo plasma exchange and take a standard glucocorticoid dose. No Plasma Exchange with Standard Glucocorticoids Glucocorticoids [Standard Dose] Participants in this arm do not undergo plasma exchange and take a standard glucocorticoid dose. Plasma Exchange with Reduced-Dose Glucocorticoids Plasma Exchange Participants in this arm undergo plasma exchange and take a reduced glucocorticoid dose. No Plasma Exchange with Reduced-Dose Glucocorticoids No Plasma Exchange Participants in this arm do not undergo plasma exchange and take a reduced glucocorticoid dose. No Plasma Exchange with Reduced-Dose Glucocorticoids Glucocorticoids [Reduced Dose] Participants in this arm do not undergo plasma exchange and take a reduced glucocorticoid dose.
- Primary Outcome Measures
Name Time Method Composite of i) All-cause Mortality or ii) End-stage Renal Disease Time frame varied by subject: minimum of 1 year - maximum of 7 years The primary outcome was a composite of death from any cause or end-stage renal disease (ESRD), defined as ≥12 continuous weeks of renal replacement therapy.
- Secondary Outcome Measures
Name Time Method Number of Participants With Sustained Remission Time frame varied by subject: minimum of 1 year - maximum of 7 years Remission that occurs before 6 months, and lasts without a first relapse until at least 12 months after randomization
Health-related Quality of Life Using the SF-36 Physical Composite 12 months Quality of life was measured using the 36-item Short Form (SF-36) physical composite scores. Scores for the scale range from 0-100 and transformed to have a mean of 50 and SD of 10 in the reference population, with higher scores indicating a better Health-related Quality of Life.
Health-related Quality of Life Using the SF-36 Mental Composite 12 months Quality of life was measured using the 36-item Short Form (SF-36) mental composite scores. Scores for the scale range from 0-100 and transformed to have a mean of 50 and SD of 10 in the reference population, with higher scores indicating a better Health-related Quality of Life.
Rate of Serious Infection Events Time frame varied by subject: minimum of 1 year - maximum of 7 years Serious infections defined as an infectious syndrome that requires intravenous antibiotics or hospitalization for treatment.
Health-related Quality of Life Using the EQ-5D Index Descriptive System 12 months EuroQoL-5 Dimensions consist of 2 elements: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D descriptive system comprised of following 5 dimensions: 1.Mobility, 2.Self-Care, 3.Usual Activities, 4.Pain/Discomfort and 5.Anxiety/Depression. Each of these 5 dimensions has 5 levels: 1: no problems; 2: slight problems; 3: moderate problems; 4: severe problems; 5: Unable to do. The digits for each of 5 dimensions were combined in a 5-digit number describing the participant's health state: e.g. state 11111 indicates no problem on any of the 5 dimensions. Health state index scores generally range from less than 0 (where 0 is a health state equivalent to death; negative values are valued as worse than death) to 1 (perfect health), with higher scores indicating higher health utility.
Trial Locations
- Locations (98)
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Concord Repatriation General Hospital
🇦🇺Concord, New South Wales, Australia
John Hunter Hospital,
🇦🇺New Lambton Heights, New South Wales, Australia
Prince of Wales Hospital
🇦🇺Randwick, New South Wales, Australia
Royal North Shore Hospital
🇦🇺St. Leonards, New South Wales, Australia
Nambour Hospital
🇦🇺Nambour, Queensland, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Royal Hobart Hospital
🇦🇺Hobart, Tasmania, Australia
Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
Gold Coast Hospital
🇦🇺Southport, Australia
St Joseph's Hospital
🇨🇦Hamilton, Ontario, Canada
The Ottawa Hospital
🇨🇦Ottawa, Ontario, Canada
St Michael's Hospital
🇨🇦Toronto, Ontario, Canada
Holstebro Hospital and University of Aarhus
🇩🇰Holstebro, Denmark
CHRU Brest Hopital La Cavale Blanche
🇫🇷Brest, France
Aarhus University Hospital
🇩🇰Aarhus, Denmark
General Faculty Hospital
🇨🇿Prague, Czechia
Centre Hospitalier de Boulogne
🇫🇷Boulogne-sur-Mer, France
Rigshospitalet
🇩🇰Copenhagen, Denmark
CHU Brest
🇫🇷Brest, France
CHU Caen - Nephrology Department
🇫🇷Caen, France
CHU Clermont-Ferrand
🇫🇷Clermont Ferrand, France
Centre Hospitalier de Mulhouse
🇫🇷Mulhouse, France
CHU D'Angers
🇫🇷D'Angers, France
Centre Hospitalier Universitaire de Grenoble
🇫🇷Grenoble, France
Hopital Bichat Claude Bernard
🇫🇷Paris, France
Hopital Site Sainte Blandine
🇫🇷Metz, France
CHU Hopital Bretonneau
🇫🇷Tours, France
Hopital Cochin
🇫🇷Paris, France
Centre Hospitalier de la Region d'Annecy
🇫🇷Pringy, France
Hopital Europeen Georges-Pompidou
🇫🇷Paris, France
CHU De Toulouse-Hotel Dieu Saint Jacques
🇫🇷Toulouse, France
Centre Hospitalier de Valenciennes
🇫🇷Valenciennes, France
Hippokration Hospital
🇬🇷Thessaloniki, Greece
University of Brescia
🇮🇹Brescia, Italy
Azienda Ospedaliero Universitaria di Parma
🇮🇹Parma, Italy
North Shore Hospital
🇳🇿Takapuna, Auckland, New Zealand
Dunedin Hospital
🇳🇿Dunedin, New Zealand
Waikato Hospital
🇳🇿Hamilton, New Zealand
Skane University Hospital
🇸🇪Malmo, Sweden
Karolinska Institute
🇸🇪Stockholm, Sweden
Linkoping University Hospital
🇸🇪Linkoping, Sweden
Aberdeen Royal Infirmary
🇬🇧Aberdeen, United Kingdom
Western Infirmary
🇬🇧Glasgow, Scotland, United Kingdom
Brighton and Sussex University Hospitals
🇬🇧Brighton, United Kingdom
Queen Elizabeth Hospital
🇬🇧Birmingham, United Kingdom
Kent and Canterbury Hospital
🇬🇧Canterbury, United Kingdom
Addenbrooke's Hospital
🇬🇧Cambridge, United Kingdom
Royal Infirmary of Edinburgh
🇬🇧Edinburgh, United Kingdom
Royal Devon & Exeter Hospital (Wonford)
🇬🇧Exeter, United Kingdom
St James's University Hospital
🇬🇧Leeds, United Kingdom
The Royal London Hospital
🇬🇧London, United Kingdom
St. George's Hospital
🇬🇧London, United Kingdom
Hammersmith Hospital
🇬🇧London, United Kingdom
Manchester Royal Infirmary
🇬🇧Manchester, United Kingdom
Freeman Hospital
🇬🇧Newcastle, United Kingdom
Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences
🇬🇧Oxford, United Kingdom
Royal Berkshire Hospital, Reading
🇬🇧Reading, United Kingdom
Churchill Hospital
🇬🇧Oxford, United Kingdom
Royal Preston Hospital
🇬🇧Preston, United Kingdom
The Geelong Hospital
🇦🇺Geelong, Victoria, Australia
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Hopital Saint-Luc
🇨🇦Montreal, Quebec, Canada
Canberra Hospital
🇦🇺Garran, Australian Capital Territory, Australia
University of Calgary
🇨🇦Calgary, Alberta, Canada
Austin Hospital
🇦🇺Heidelberg, Victoria, Australia
The Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
St Paul's Hospital
🇨🇦Vancouver, British Columbia, Canada
University of Alberta
🇨🇦Edmonton, Alberta, Canada
University Hospitals Leuven
🇧🇪Leuven, Belgium
University of Tsukuba
🇯🇵Tsukuba, Ibaraki, Japan
Kyoto University Hospital
🇯🇵Kyoto, Japan
Teikyo University Hospital
🇯🇵Tokyo, Japan
St Olavs Hospital, Trondheim University Hospital
🇳🇴Trondheim, Norway
University of Miyazaki Hospital
🇯🇵Miyazaki, Japan
Kitano Hospital
🇯🇵Osaka, Japan
Tokyo Metropolitan Geriatric Hospital
🇯🇵Tokyo, Japan
Instituto Nacional de Enfermedades Respiratorias
🇲🇽Mexico City, Mexico
University Hospital North Norway HF
🇳🇴Tromsø, Norway
Fremantle Hospital,
🇦🇺Fremantle,, Western Australia, Australia
Herlev Hospital
🇩🇰Copenhagen, Denmark
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Boston University School of Medicine
🇺🇸Boston, Massachusetts, United States
Royal Brisbane and Women's Hospital
🇦🇺Herston, Queensland, Australia
Flinders Medical Centre,
🇦🇺Adelaide, South Australia, Australia
Mount Sinai Hospital
🇨🇦Toronto, Ontario, Canada
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
St Vincent's Hospital
🇦🇺Fitzroy, Victoria, Australia
Royal Free Hospital
🇬🇧London, United Kingdom
Colmar Hospital - Nephrology
🇫🇷Colmar, France
London Health Sciences Centre
🇨🇦London, Ontario, Canada
University Hospitals Coventry and Warwickshire NHS Trust
🇬🇧Coventry, United Kingdom
Royal Liverpool University Hospital
🇬🇧Liverpool, United Kingdom