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Plasma Exchange and Glucocorticoids for Treatment of Anti-Neutrophil Cytoplasm Antibody (ANCA) - Associated Vasculitis (PEXIVAS)
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
| Granulomatosis With Polyangiitis (Wegener's) (GPA) Microscopic Polyangiitis (MPA) | Procedure: Plasma Exchange Drug: Glucocorticoids | Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Factorial Assignment Masking: None (Open Label) Primary Purpose: Treatment |
| Official Title: | Plasma Exchange and Glucocorticoid Dosing in the Treatment of Anti-neutrophil Cytoplasm Antibody Associated Vasculitis: an International Randomized Controlled Trial |
- All-cause mortality [ Time Frame: 2 years after the final subject is enrolled ]
- End-stage renal disease [ Time Frame: 2 years after final subject is enrolled ]
- Sustained remission [ Time Frame: 2 years after the final subject is enrolled ]Remission that occurs before 6 months, and lasts without a first relapse until at least 12 months after randomization
- Rate of serious infections [ Time Frame: 12 months after first subject enrolled and at study end ]
- Health-related quality of life using the SF-36 Physical Composite, Mental Composite and EQ-5D Index Score [ Time Frame: 12 months after study enrollment is completed ]
| Enrollment: | 704 |
| Study Start Date: | May 2010 |
| Estimated Study Completion Date: | April 2018 |
| Estimated Primary Completion Date: | April 2018 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
No Plasma Exchange
Participants in this arm do not undergo plasma exchange
|
Drug: Glucocorticoids
During the study, a standard glucocorticoids dose regimen will be compared to a reduced glucocorticoids dose regimen. All subjects' patients will receive the same glucocorticoids dose for the first two weeks then the dose will decrease following either a standard regimen or a reduced regimen.
|
| Experimental: Plasma Exchange |
Procedure: Plasma Exchange
Plasma exchange is a procedure whereby blood is taken from the body and separated by a machine into blood cells and plasma, which is the liquid part of blood. The plasma is discarded and the blood cells are returned to the body with a plasma substitute.
Drug: Glucocorticoids
During the study, a standard glucocorticoids dose regimen will be compared to a reduced glucocorticoids dose regimen. All subjects' patients will receive the same glucocorticoids dose for the first two weeks then the dose will decrease following either a standard regimen or a reduced regimen.
|
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;
- Plasma exchange - 7 exchanges and, either standard or low-dose glucocorticoids or
- No plasma exchange and, either standard or low-dose glucocorticoids
All studies will receive standard remission-induction therapy with either cyclophosphamide or rituximab.
Eligibility| Ages Eligible for Study: | 15 Years and older (Child, Adult, Senior) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
• 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 with both:
- 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
Exclusion Criteria:
- A diagnosis of vasculitis other than granulomatosis with polyangiitis or microscopic polyangiitis
- Positive 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
- Inability or unwillingness to comply with birth control/abstinence
- 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
Contacts and LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT00987389
Show 98 Study Locations
| Principal Investigator: | David Jayne, MD | Cambridge University Hospitals NHS Foundation Trust |
| Principal Investigator: | Peter Merkel, MD, MPH | University of Pennsylvania |
| Principal Investigator: | Michael Walsh, MD | McMaster University |
| Study Chair: | Xavier Puéchal, MD, PhD | Assistance Publique - Hôpitaux de Paris |
More Information
Additional Information:
Publications:
| Responsible Party: | Peter Merkel, Professor, University of Pennsylvania |
| ClinicalTrials.gov Identifier: | NCT00987389 History of Changes |
| Other Study ID Numbers: |
PEXIVAS R01FD00351604 ( Other Grant/Funding Number: Food and Drug Administration (FDA) ) |
| Study First Received: | September 23, 2009 |
| Last Updated: | May 19, 2017 |
Keywords provided by Peter Merkel, University of Pennsylvania:
|
Vasculitis Granulomatosis with Polyangiitis Microscopic Polyangiitis Wegener's ANCA-Associated Vasculitis GPA |
MPA Treatment Plasma exchange Glucocorticoids ANCA-Positive |
Additional relevant MeSH terms:
|
Vasculitis Systemic Vasculitis Granulomatosis with Polyangiitis Microscopic Polyangiitis Vascular Diseases Cardiovascular Diseases Lung Diseases, Interstitial Lung Diseases Respiratory Tract Diseases Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis Autoimmune Diseases Immune System Diseases |
Cerebral Small Vessel Diseases Cerebrovascular Disorders Brain Diseases Central Nervous System Diseases Nervous System Diseases Antibodies Glucocorticoids Immunologic Factors Physiological Effects of Drugs Hormones Hormones, Hormone Substitutes, and Hormone Antagonists |
ClinicalTrials.gov processed this record on September 21, 2017