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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00987389




Trial ID
NCT00987389
Ethics application status
Date submitted
23/09/2009
Date registered
28/09/2009
Date last updated
14/03/2018

Titles & IDs
Public title
Plasma Exchange and Glucocorticoids for Treatment of Anti-Neutrophil Cytoplasm Antibody (ANCA) - Associated Vasculitis
Scientific title
Plasma Exchange and Glucocorticoid Dosing in the Treatment of Anti-neutrophil Cytoplasm Antibody Associated Vasculitis: an International Randomized Controlled Trial
Secondary ID [1] 0 0
R01FD00351604
Secondary ID [2] 0 0
PEXIVAS
Universal Trial Number (UTN)
Trial acronym
PEXIVAS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Granulomatosis With Polyangiitis (Wegener's) (GPA) 0 0
Microscopic Polyangiitis (MPA) 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - Plasma Exchange
Treatment: Drugs - Glucocorticoids

Other: No Plasma Exchange - Participants in this arm do not undergo plasma exchange

Experimental: Plasma Exchange -


Treatment: Surgery: 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.

Treatment: Drugs: 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.

Intervention code [1] 0 0
Treatment: Surgery
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Composite of i) all-cause mortality or ii) End-stage renal disease
Timepoint [1] 0 0
2 years after the final subject is enrolled
Secondary outcome [1] 0 0
Sustained remission - Remission that occurs before 6 months, and lasts without a first relapse until at least 12 months after randomization
Timepoint [1] 0 0
2 years after the final subject is enrolled
Secondary outcome [2] 0 0
Rate of serious infections
Timepoint [2] 0 0
12 months after first subject enrolled and at study end
Secondary outcome [3] 0 0
Health-related quality of life using the SF-36 Physical Composite, Mental Composite and EQ-5D Index Score
Timepoint [3] 0 0
12 months after study enrollment is completed

Eligibility
Key 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:

1. 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

2. 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

3. 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
Minimum age
15 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Factorial
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Canberra Hospital - Garran
Recruitment hospital [2] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [3] 0 0
John Hunter Hospital, - New Lambton Heights
Recruitment hospital [4] 0 0
Prince of Wales Hospital - Randwick
Recruitment hospital [5] 0 0
Royal North Shore Hospital - St. Leonards
Recruitment hospital [6] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [7] 0 0
Nambour Hospital - Nambour
Recruitment hospital [8] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [9] 0 0
Flinders Medical Centre, - Adelaide
Recruitment hospital [10] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [11] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [12] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [13] 0 0
St Vincent's Hospital - Fitzroy
Recruitment hospital [14] 0 0
The Geelong Hospital - Geelong
Recruitment hospital [15] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [16] 0 0
The Royal Melbourne Hospital - Parkville
Recruitment hospital [17] 0 0
Fremantle Hospital, - Fremantle,
Recruitment hospital [18] 0 0
Gold Coast Hospital - Southport
Recruitment postcode(s) [1] 0 0
- Garran
Recruitment postcode(s) [2] 0 0
- Concord
Recruitment postcode(s) [3] 0 0
- New Lambton Heights
Recruitment postcode(s) [4] 0 0
- Randwick
Recruitment postcode(s) [5] 0 0
- St. Leonards
Recruitment postcode(s) [6] 0 0
- Herston
Recruitment postcode(s) [7] 0 0
- Nambour
Recruitment postcode(s) [8] 0 0
- Woolloongabba
Recruitment postcode(s) [9] 0 0
- Adelaide
Recruitment postcode(s) [10] 0 0
- Hobart
Recruitment postcode(s) [11] 0 0
- Clayton
Recruitment postcode(s) [12] 0 0
- Fitzroy
Recruitment postcode(s) [13] 0 0
- Geelong
Recruitment postcode(s) [14] 0 0
- Heidelberg
Recruitment postcode(s) [15] 0 0
- Parkville
Recruitment postcode(s) [16] 0 0
- Fremantle,
Recruitment postcode(s) [17] 0 0
- Southport
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
Minnesota
Country [4] 0 0
United States of America
State/province [4] 0 0
Missouri
Country [5] 0 0
United States of America
State/province [5] 0 0
North Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Virginia
Country [9] 0 0
Belgium
State/province [9] 0 0
Leuven
Country [10] 0 0
Canada
State/province [10] 0 0
Alberta
Country [11] 0 0
Canada
State/province [11] 0 0
British Columbia
Country [12] 0 0
Canada
State/province [12] 0 0
Ontario
Country [13] 0 0
Canada
State/province [13] 0 0
Quebec
Country [14] 0 0
Czechia
State/province [14] 0 0
Prague
Country [15] 0 0
Denmark
State/province [15] 0 0
Aarhus
Country [16] 0 0
Denmark
State/province [16] 0 0
Copenhagen
Country [17] 0 0
Denmark
State/province [17] 0 0
Holstebro
Country [18] 0 0
France
State/province [18] 0 0
Boulogne-sur-Mer
Country [19] 0 0
France
State/province [19] 0 0
Brest
Country [20] 0 0
France
State/province [20] 0 0
Caen
Country [21] 0 0
France
State/province [21] 0 0
Clermont Ferrand
Country [22] 0 0
France
State/province [22] 0 0
Colmar
Country [23] 0 0
France
State/province [23] 0 0
D'Angers
Country [24] 0 0
France
State/province [24] 0 0
Grenoble
Country [25] 0 0
France
State/province [25] 0 0
Metz
Country [26] 0 0
France
State/province [26] 0 0
Mulhouse
Country [27] 0 0
France
State/province [27] 0 0
Paris
Country [28] 0 0
France
State/province [28] 0 0
Pringy
Country [29] 0 0
France
State/province [29] 0 0
Toulouse
Country [30] 0 0
France
State/province [30] 0 0
Tours
Country [31] 0 0
France
State/province [31] 0 0
Valenciennes
Country [32] 0 0
Greece
State/province [32] 0 0
Thessaloniki
Country [33] 0 0
Italy
State/province [33] 0 0
Brescia
Country [34] 0 0
Italy
State/province [34] 0 0
Parma
Country [35] 0 0
Japan
State/province [35] 0 0
Ibaraki
Country [36] 0 0
Japan
State/province [36] 0 0
Kyoto
Country [37] 0 0
Japan
State/province [37] 0 0
Miyazaki
Country [38] 0 0
Japan
State/province [38] 0 0
Osaka
Country [39] 0 0
Japan
State/province [39] 0 0
Tokyo
Country [40] 0 0
Mexico
State/province [40] 0 0
Mexico City
Country [41] 0 0
New Zealand
State/province [41] 0 0
Auckland
Country [42] 0 0
New Zealand
State/province [42] 0 0
Dunedin
Country [43] 0 0
New Zealand
State/province [43] 0 0
Hamilton
Country [44] 0 0
Norway
State/province [44] 0 0
Tromsø
Country [45] 0 0
Norway
State/province [45] 0 0
Trondheim
Country [46] 0 0
Sweden
State/province [46] 0 0
Linkoping
Country [47] 0 0
Sweden
State/province [47] 0 0
Malmo
Country [48] 0 0
Sweden
State/province [48] 0 0
Stockholm
Country [49] 0 0
United Kingdom
State/province [49] 0 0
Scotland
Country [50] 0 0
United Kingdom
State/province [50] 0 0
Aberdeen
Country [51] 0 0
United Kingdom
State/province [51] 0 0
Birmingham
Country [52] 0 0
United Kingdom
State/province [52] 0 0
Brighton
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Cambridge
Country [54] 0 0
United Kingdom
State/province [54] 0 0
Canterbury
Country [55] 0 0
United Kingdom
State/province [55] 0 0
Coventry
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Edinburgh
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Exeter
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Leeds
Country [59] 0 0
United Kingdom
State/province [59] 0 0
Liverpool
Country [60] 0 0
United Kingdom
State/province [60] 0 0
London
Country [61] 0 0
United Kingdom
State/province [61] 0 0
Manchester
Country [62] 0 0
United Kingdom
State/province [62] 0 0
Newcastle
Country [63] 0 0
United Kingdom
State/province [63] 0 0
Oxford
Country [64] 0 0
United Kingdom
State/province [64] 0 0
Preston
Country [65] 0 0
United Kingdom
State/province [65] 0 0
Reading

Funding & Sponsors
Primary sponsor type
Other
Name
University of Pennsylvania
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Cambridge University Hospitals NHS Foundation Trust
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
University of Birmingham
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Government body
Name [3] 0 0
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00987389
Trial related presentations / 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.
Public notes

Contacts
Principal investigator
Name 0 0
David Jayne, MD
Address 0 0
Cambridge University Hospitals NHS Foundation Trust
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries