Granulomatosis With Polyangiitis (Wegener's) (GPA)Phase 3PEXIVASNCT00987389
Plasma Exchange and Glucocorticoids for Treatment of Anti-Neutrophil Cytoplasm Antibody (ANCA) - Associated Vasculitis
A Phase 3 study testing Plasma Exchange, No Plasma Exchange and Glucocorticoids [Standard Dose] in people with Granulomatosis With Polyangiitis (Wegener's) (GPA) and Microscopic Polyangiitis (MPA), run by University of Pennsylvania at 98 sites in 15 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Granulomatosis With Polyangiitis (Wegener's) (GPA), Microscopic Polyangiitis (MPA)
- What is being tested?
- Plasma Exchange, No Plasma Exchange and Glucocorticoids [Standard Dose]
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 704 participants
- Where
- 98 sitesin 15 countries
- Study dates
- May 2010to Aug 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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:
Show all 20Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
98 sites in 15 countries.
98 sites in 15 countries
United Kingdom21 sites
Aberdeen Royal Infirmary
Aberdeen, AB25 2
Queen Elizabeth Hospital
Birmingham, B15 2TQ
Brighton and Sussex University Hospitals
Brighton, BN2 5BE
Addenbrooke's Hospital
Cambridge, CB22QQ
Kent and Canterbury Hospital
Canterbury
University Hospitals Coventry and Warwickshire NHS Trust
Coventry, CV2 2DX
Royal Infirmary of Edinburgh
Edinburgh, EH16 4SA
Royal Devon & Exeter Hospital (Wonford)
Exeter
Western Infirmary
Glasgow, Scotland
St James's University Hospital
Leeds
Royal Liverpool University Hospital
Liverpool, L7 8XP
Royal Free Hospital
London, NW3 2QG
The Royal London Hospital
London, SE1 2PR
St. George's Hospital
London, SW17 0QT
Hammersmith Hospital
London, W12 0HS
Manchester Royal Infirmary
Manchester
Freeman Hospital
Newcastle
Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences
Oxford, OX3 7LD
Churchill Hospital
Oxford, OX3 7LJ
Royal Preston Hospital
Preston, PR2 9HT
Royal Berkshire Hospital, Reading
Reading, RG1 5AQ
Australia18 sites
Flinders Medical Centre,
Adelaide, South Australia
Royal Adelaide Hospital
Adelaide, South Australia
Monash Medical Centre
Clayton, Victoria
Concord Repatriation General Hospital
Concord, New South Wales
St Vincent's Hospital
Fitzroy, Victoria
Fremantle Hospital,
Fremantle, Western Australia
Canberra Hospital
Garran, Australian Capital Territory
The Geelong Hospital
Geelong, Victoria
Austin Hospital
Heidelberg, Victoria
Royal Brisbane and Women's Hospital
Herston, Queensland
Royal Hobart Hospital
Hobart, Tasmania
Nambour Hospital
Nambour, Queensland
John Hunter Hospital,
New Lambton Heights, New South Wales
The Royal Melbourne Hospital
Parkville, Victoria
Prince of Wales Hospital
Randwick, New South Wales
Gold Coast Hospital
Southport
Royal North Shore Hospital
St Leonards, New South Wales
Princess Alexandra Hospital
Woolloongabba, Queensland
France17 sites
Centre Hospitalier de Boulogne
Boulogne-sur-Mer
CHRU Brest Hopital La Cavale Blanche
Brest
CHU Brest
Brest
CHU Caen - Nephrology Department
Caen
CHU Clermont-Ferrand
Clermont-Ferrand
Colmar Hospital - Nephrology
Colmar
CHU D'Angers
D'Angers
Centre Hospitalier Universitaire de Grenoble
Grenoble
Hopital Site Sainte Blandine
Metz
Centre Hospitalier de Mulhouse
Mulhouse
Hopital Bichat Claude Bernard
Paris
Hopital Cochin
Paris
Hopital Europeen Georges-Pompidou
Paris
Centre Hospitalier de la Region d'Annecy
Pringy
CHU De Toulouse-Hotel Dieu Saint Jacques
Toulouse
CHU Hopital Bretonneau
Tours
Centre Hospitalier de Valenciennes
Valenciennes
United States9 sites
Boston University School of Medicine
Boston, Massachusetts, 02118
University of North Carolina
Chapel Hill, North Carolina, 27599
University of Virginia
Charlottesville, Virginia, 22904
Cleveland Clinic
Cleveland, Ohio, 44195
Cedars-Sinai Medical Center
Los Angeles, California, 90048
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Mayo Clinic
Rochester, Minnesota, 55905
Washington University School of Medicine
St Louis, Missouri
Canada9 sites
University of Calgary
Calgary, Alberta
University of Alberta
Edmonton, Alberta
St Joseph's Hospital
Hamilton, Ontario
London Health Sciences Centre
London, Ontario
Hopital Saint-Luc
Montreal, Quebec, H2X 3J4
The Ottawa Hospital
Ottawa, Ontario
Mount Sinai Hospital
Toronto, Ontario
St Michael's Hospital
Toronto, Ontario
St Paul's Hospital
Vancouver, British Columbia
Japan6 sites
Kyoto University Hospital
Kyoto, 606-8507
University of Miyazaki Hospital
Miyazaki
Kitano Hospital
Osaka
Teikyo University Hospital
Tokyo
Tokyo Metropolitan Geriatric Hospital
Tokyo
University of Tsukuba
Tsukuba, Ibaraki, 305-8572
Denmark4 sites
Aarhus University Hospital
Aarhus
Herlev Hospital
Copenhagen
Rigshospitalet
Copenhagen
Holstebro Hospital and University of Aarhus
Holstebro
New Zealand3 sites
Dunedin Hospital
Dunedin
Waikato Hospital
Hamilton, 3204
North Shore Hospital
Takapuna, Auckland
Sweden3 sites
Linkoping University Hospital
Linköping
Skane University Hospital
Malmö
Karolinska Institute
Stockholm
Italy2 sites
University of Brescia
Brescia
Azienda Ospedaliero Universitaria di Parma
Parma
Norway2 sites
University Hospital North Norway HF
Tromsø
St Olavs Hospital, Trondheim University Hospital
Trondheim
About this study
Official title: Plasma Exchange and Glucocorticoid Dosing in the Treatment of Anti-neutrophil Cytoplasm Antibody Associated Vasculitis: an International Randomized Controlled Trial
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.
Read the 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.
- Being tested
- Plasma Exchange, No Plasma Exchange, Glucocorticoids [Standard Dose], Glucocorticoids [Reduced Dose]
- Keywords
- Vasculitis, Granulomatosis with Polyangiitis, Microscopic Polyangiitis, Wegener's, ANCA-Associated Vasculitis, GPA, MPA, Treatment, Plasma exchange, Glucocorticoids, ANCA-Positive
- Medical subject headings
- Granulomatosis with Polyangiitis, Microscopic Polyangiitis, Vasculitis, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Plasma ExchangeProcedure or surgery
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.
No Plasma ExchangeOther
No plasma exchange.
Glucocorticoids [Standard Dose]Drug
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 a standard regimen.
Glucocorticoids [Reduced Dose]Drug
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 a reduced regimen.
| Study group | Role | What they receive |
|---|---|---|
| Plasma Exchange with Standard Glucocorticoids | Experimental | Participants in this arm undergo plasma exchange and take a standard glucocorticoid dose. Receives: Procedure: Plasma Exchange; Drug: Glucocorticoids [Standard Dose] |
| No Plasma Exchange with Standard Glucocorticoids | Active comparator | Participants in this arm do not undergo plasma exchange and take a standard glucocorticoid dose. Receives: Other: No Plasma Exchange; Drug: Glucocorticoids [Standard Dose] |
| Plasma Exchange with Reduced-Dose Glucocorticoids | Experimental | Participants in this arm undergo plasma exchange and take a reduced glucocorticoid dose. Receives: Procedure: Plasma Exchange; Drug: Glucocorticoids [Reduced Dose] |
| No Plasma Exchange with Reduced-Dose Glucocorticoids | Active comparator | Participants in this arm do not undergo plasma exchange and take a reduced glucocorticoid dose. Receives: Other: No Plasma Exchange; Drug: Glucocorticoids [Reduced Dose] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite of i) All-cause Mortality or ii) End-stage Renal Disease
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.
Measured: Time frame varied by subject: minimum of 1 year - maximum of 7 years
Secondary outcomes (5)
Number of Participants With Sustained Remission
Remission that occurs before 6 months, and lasts without a first relapse until at least 12 months after randomization
Measured: Time frame varied by subject: minimum of 1 year - maximum of 7 years
Rate of Serious Infection Events
Serious infections defined as an infectious syndrome that requires intravenous antibiotics or hospitalization for treatment.
Measured: Time frame varied by subject: minimum of 1 year - maximum of 7 years
Health-related Quality of Life Using the SF-36 Physical Composite
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.
Measured: 12 months
Health-related Quality of Life Using the SF-36 Mental Composite
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.
Measured: 12 months
Health-related Quality of Life Using the EQ-5D Index Descriptive System
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.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2009 (estimated)
- Study startMay 2010
- Primary completionAug 2017
- Study completionAug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Granulomatosis With Polyangiitis (Wegener's) (GPA)Studies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 704 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- Cambridge University Hospitals NHS Foundation Trust, University of Birmingham, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Responsible party
- Principal investigator, Peter Merkel, University of Pennsylvania
- Investigators
- David Jayne, MD, Principal investigator, Cambridge University Hospitals NHS Foundation TrustPeter Merkel, MD, MPH, Principal investigator, University of PennsylvaniaMichael Walsh, MD, Principal investigator, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00987389
- Sponsor's protocol ID
- PEXIVAS
- Other IDs
- R01FD00351604, 2009-013220-24, 2009
- Acronym
- PEXIVAS
- Status last verified
- May 2020
- First submitted
- 23 Sep 2009
- Last updated
- 26 May 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Walsh M, Merkel PA, Peh CA, Szpirt W, Guillevin L, Pusey CD, De Zoysa J, Ives N, Clark WF, Quillen K, Winters JL, Wheatley K, Jayne D; PEXIVAS Investigators. Plasma exchange and glucocorticoid dosing in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis (PEXIVAS): protocol for a randomized controlled trial. Trials. 2013 Mar 14;14:73. doi: 10.1186/1745-6215-14-73.
PubMed 23497590Walsh M, Merkel PA, Peh CA, Szpirt WM, Puechal X, Fujimoto S, Hawley CM, Khalidi N, Flossmann O, Wald R, Girard LP, Levin A, Gregorini G, Harper L, Clark WF, Pagnoux C, Specks U, Smyth L, Tesar V, Ito-Ihara T, de Zoysa JR, Szczeklik W, Flores-Suarez LF, Carette S, Guillevin L, Pusey CD, Casian AL, Brezina B, Mazzetti A, McAlear CA, Broadhurst E, Reidlinger D, Mehta S, Ives N, Jayne DRW; PEXIVAS Investigators. Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis. N Engl J Med. 2020 Feb 13;382(7):622-631. doi: 10.1056/NEJMoa1803537.
PubMed 32053298Fussner LA, Flores-Suarez LF, Cartin-Ceba R, Specks U, Cox PG, Jayne DRW, Merkel PA, Walsh M; PEXIVAS Investigators. Alveolar Hemorrhage in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Results of an International Randomized Controlled Trial (PEXIVAS). Am J Respir Crit Care Med. 2024 May 1;209(9):1141-1151. doi: 10.1164/rccm.202308-1426OC.
PubMed 38346237Jayne D, Walsh M, Merkel PA, Peh CA, Szpirt W, Puechal X, Fujimoto S, Hawley C, Khalidi N, Jones R, Flossmann O, Wald R, Girard L, Levin A, Gregorini G, Harper L, Clark W, Pagnoux C, Specks U, Smyth L, Ito-Ihara T, de Zoysa J, Brezina B, Mazzetti A, McAlear CA, Reidlinger D, Mehta S, Ives N, Brettell EA, Jarrett H, Wheatley K, Broadhurst E, Casian A, Pusey CD. Plasma exchange and glucocorticoids to delay death or end-stage renal disease in anti-neutrophil cytoplasm antibody-associated vasculitis: PEXIVAS non-inferiority factorial RCT. Health Technol Assess. 2022 Sep;26(38):1-60. doi: 10.3310/PNXB5040.
PubMed 36155131
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Plasma Exchange and Glucocorticoid Dosing in the Treatment of Anti-neutrophil Cytoplasm Antibody Associated Vasculitis: an International Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT00987389
- Acronym / sponsor ID
- PEXIVAS / PEXIVAS
- Keywords
- Vasculitis, Granulomatosis with Polyangiitis, Microscopic Polyangiitis, Wegener's, ANCA-Associated Vasculitis, GPA, MPA, Treatment
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 704 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- Cambridge University Hospitals NHS Foundation Trust, University of Birmingham, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Study start
- May 2010 (actual)
- Primary completion
- Aug 2017 (actual)
- Study completion
- Aug 2017 (actual)
- First posted
- 30 Sep 2009 (estimated)
- Results
- Posted 26 May 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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;
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Plasma Exchange with Standard Glucocorticoids | Experimental | Procedure: Plasma Exchange, Drug: Glucocorticoids [Standard Dose]Participants in this arm undergo plasma exchange and take a standard glucocorticoid dose. |
| No Plasma Exchange with Standard Glucocorticoids | Active comparator | Other: No Plasma Exchange, Drug: Glucocorticoids [Standard Dose]Participants in this arm do not undergo plasma exchange and take a standard glucocorticoid dose. |
| Plasma Exchange with Reduced-Dose Glucocorticoids | Experimental | Procedure: Plasma Exchange, Drug: Glucocorticoids [Reduced Dose]Participants in this arm undergo plasma exchange and take a reduced glucocorticoid dose. |
| No Plasma Exchange with Reduced-Dose Glucocorticoids | Active comparator | Other: No Plasma Exchange, Drug: Glucocorticoids [Reduced Dose]Participants in this arm do not undergo plasma exchange and take a reduced glucocorticoid dose. |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (20 listed)
- 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:
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Plasma ExchangePlasma 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. | Procedure or surgery | Plasma Exchange with Reduced-Dose Glucocorticoids, Plasma Exchange with Standard Glucocorticoids |
| No Plasma ExchangeNo plasma exchange. | Other | No Plasma Exchange with Reduced-Dose Glucocorticoids, No Plasma Exchange with Standard Glucocorticoids |
| Glucocorticoids [Standard Dose]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 a standard regimen. | Drug | No Plasma Exchange with Standard Glucocorticoids, Plasma Exchange with Standard Glucocorticoids |
| Glucocorticoids [Reduced Dose]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 a reduced regimen. | Drug | No Plasma Exchange with Reduced-Dose Glucocorticoids, Plasma Exchange with Reduced-Dose Glucocorticoids |
Primary outcome
Composite of i) All-cause Mortality or ii) End-stage Renal Disease
Time frame: 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.
5 secondary outcomes
Number of Participants With Sustained Remission
Time frame: Time frame varied by subject: minimum of 1 year - maximum of 7 years
Rate of Serious Infection Events
Time frame: Time frame varied by subject: minimum of 1 year - maximum of 7 years
Health-related Quality of Life Using the SF-36 Physical Composite
Time frame: 12 months
Health-related Quality of Life Using the SF-36 Mental Composite
Time frame: 12 months
Health-related Quality of Life Using the EQ-5D Index Descriptive System
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 May 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23497590Walsh M, Merkel PA, Peh CA, Szpirt W, Guillevin L, Pusey CD, De Zoysa J, Ives N, Clark WF, Quillen K, Winters JL, Wheatley K, Jayne D; PEXIVAS Investigators. Plasma exchange and glucocorticoid dosing in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis (PEXIVAS): protocol for a randomized controlled trial. Trials. 2013 Mar 14;14:73. doi: 10.1186/1745-6215-14-73.
- Results publication: PubMed 32053298Walsh M, Merkel PA, Peh CA, Szpirt WM, Puechal X, Fujimoto S, Hawley CM, Khalidi N, Flossmann O, Wald R, Girard LP, Levin A, Gregorini G, Harper L, Clark WF, Pagnoux C, Specks U, Smyth L, Tesar V, Ito-Ihara T, de Zoysa JR, Szczeklik W, Flores-Suarez LF, Carette S, Guillevin L, Pusey CD, Casian AL, Brezina B, Mazzetti A, McAlear CA, Broadhurst E, Reidlinger D, Mehta S, Ives N, Jayne DRW; PEXIVAS Investigators. Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis. N Engl J Med. 2020 Feb 13;382(7):622-631. doi: 10.1056/NEJMoa1803537.
- Derived from this study: PubMed 38346237Fussner LA, Flores-Suarez LF, Cartin-Ceba R, Specks U, Cox PG, Jayne DRW, Merkel PA, Walsh M; PEXIVAS Investigators. Alveolar Hemorrhage in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Results of an International Randomized Controlled Trial (PEXIVAS). Am J Respir Crit Care Med. 2024 May 1;209(9):1141-1151. doi: 10.1164/rccm.202308-1426OC.
- Derived from this study: PubMed 36155131Jayne D, Walsh M, Merkel PA, Peh CA, Szpirt W, Puechal X, Fujimoto S, Hawley C, Khalidi N, Jones R, Flossmann O, Wald R, Girard L, Levin A, Gregorini G, Harper L, Clark W, Pagnoux C, Specks U, Smyth L, Ito-Ihara T, de Zoysa J, Brezina B, Mazzetti A, McAlear CA, Reidlinger D, Mehta S, Ives N, Brettell EA, Jarrett H, Wheatley K, Broadhurst E, Casian A, Pusey CD. Plasma exchange and glucocorticoids to delay death or end-stage renal disease in anti-neutrophil cytoplasm antibody-associated vasculitis: PEXIVAS non-inferiority factorial RCT. Health Technol Assess. 2022 Sep;26(38):1-60. doi: 10.3310/PNXB5040.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Jayne, MD principal investigator
Cambridge University Hospitals NHS Foundation Trust
Peter Merkel, MD, MPH principal investigator
University of Pennsylvania
Michael Walsh, MD principal investigator
McMaster University
98 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Plasma Exchange, No Plasma Exchange and Glucocorticoids [Standard Dose] in people with Granulomatosis With Polyangiitis (Wegener's) (GPA) and Microscopic Polyangiitis (MPA), run by University of Pennsylvania at 98 sites in 15 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 98 sites in United Kingdom, Australia, France, United States, Canada and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 May 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite of i) All-cause Mortality or ii) End-stage Renal Disease (time frame: Time frame varied by subject: minimum of 1 year - maximum of 7 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00987389, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 May 2020.