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Plasma Exchange and Glucocorticoids for Treatment of Anti-Neutrophil Cytoplasm Antibody (ANCA) - Associated Vasculitis (PEXIVAS)

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ClinicalTrials.gov Identifier: NCT00987389
Recruitment Status : Completed
First Posted : September 30, 2009
Results First Posted : May 26, 2020
Last Update Posted : May 26, 2020
Sponsor:
Collaborators:
Cambridge University Hospitals NHS Foundation Trust
University of Birmingham
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Information provided by (Responsible Party):
Peter Merkel, University of Pennsylvania

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Factorial Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Granulomatosis With Polyangiitis (Wegener's) (GPA)
Microscopic Polyangiitis (MPA)
Interventions Procedure: Plasma Exchange
Other: No Plasma Exchange
Drug: Glucocorticoids [Standard Dose]
Drug: Glucocorticoids [Reduced Dose]
Enrollment 704
Recruitment Details  
Pre-assignment Details 704 subjects were enrolled into the study and randomized to either plasma exchange or no plasma exchange, and randomized to receive either standard dose GC or reduced dose GC.
Arm/Group Title Plasma Exchange With Standard Glucocorticoids Plasma Exchange With Reduced Glucocorticoids No Plasma Exchange With Standard Glucocorticoids No Plasma Exchange With Reduced Glucocorticoid
Hide Arm/Group Description

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.

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 will follow a standard regimen.

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.

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 to a reduced regimen.

Participants in this arm do not undergo plasma exchange.

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 follow a standard regimen.

Participants in this arm do not undergo plasma exchange.

All subjects' received the same glucocorticoids dose for the first two weeks, then the dose was decreased following a reduced glucocorticoid dose regimen.

Period Title: Overall Study
Started 176 176 175 177
Completed 167 168 167 174
Not Completed 9 8 8 3
Reason Not Completed
Ineligible             0             3             0             0
Lost to Follow-up             4             1             3             1
Withdrawal by Subject             4             3             2             1
Withdrawn from Treatment             0             1             0             0
Multiple different reasons             1             0             3             1
Arm/Group Title Plasma Exchange No Plasma Exchange Total
Hide Arm/Group Description 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. Participants in this arm do not undergo plasma exchange. Total of all reporting groups
Overall Number of Baseline Participants 352 352 704
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 352 participants 352 participants 704 participants
62.8  (14.4) 63.5  (13.7) 63.2  (14)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 352 participants 352 participants 704 participants
Female 149 158 307
Male 203 194 397
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 352 participants 352 participants 704 participants
South Asian 7 15 22
Arab 0 1 1
Chinese 1 5 6
Japanese 6 6 12
Other Asian 0 2 2
Black African 4 2 6
Coloured African 0 1 1
Other Black 5 2 7
European 281 277 558
Latin America 5 5 10
Native N/S American or Aborigine 16 7 23
Other 24 28 52
Missing 3 1 4
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 352 participants 352 participants 704 participants
United States 24 15 39
Czechia 7 3 10
Japan 6 6 12
United Kingdom 88 91 179
New Zealand 6 4 10
Canada 97 94 191
Sweden 5 4 9
Belgium 1 0 1
Norway 0 8 8
Denmark 25 32 57
Italy 18 8 26
Mexico 4 3 7
Australia 44 50 94
France 21 31 52
Poland 5 2 7
Spain 1 1 2
ANCA Binding Specificity: PR3  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 352 participants 352 participants 704 participants
143 143 286
ANCA Binding Specificity: MPO  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 352 participants 352 participants 704 participants
209
  59.4%
209
  59.4%
418
  59.4%
Severity of Renal Disease at Presentation: Creatinine <500umol/min  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 352 participants 352 participants 704 participants
251 248 499
Severity of Renal Disease at Presentation: Requiring Dialysis or Creatinine >=500umol/min  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 352 participants 352 participants 704 participants
101 104 205
1.Primary Outcome
Title Composite of i) All-cause Mortality or ii) End-stage Renal Disease
Hide Description 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.
Time Frame Time frame varied by subject: minimum of 1 year - maximum of 7 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Plasma Exchange No Plasma Exchange
Hide Arm/Group Description:

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.

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.

Participants in this arm do not undergo plasma exchange

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.

Overall Number of Participants Analyzed 352 352
Measure Type: Count of Participants
Unit of Measure: Participants
100
  28.4%
109
  31.0%
2.Secondary Outcome
Title Number of Participants With Sustained Remission
Hide Description Remission that occurs before 6 months, and lasts without a first relapse until at least 12 months after randomization
Time Frame Time frame varied by subject: minimum of 1 year - maximum of 7 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Plasma Exchange No Plasma Exchange
Hide Arm/Group Description:

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.

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.

Participants in this arm do not undergo plasma exchange

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.

Overall Number of Participants Analyzed 352 352
Measure Type: Count of Participants
Unit of Measure: Participants
200
  56.8%
197
  56.0%
3.Secondary Outcome
Title Rate of Serious Infection Events
Hide Description Serious infections defined as an infectious syndrome that requires intravenous antibiotics or hospitalization for treatment.
Time Frame Time frame varied by subject: minimum of 1 year - maximum of 7 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Plasma Exchange No Plasma Exchange
Hide Arm/Group Description:

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.

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.

Participants in this arm do not undergo plasma exchange

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.

Overall Number of Participants Analyzed 352 352
Measure Type: Number
Unit of Measure: events
145 132
4.Secondary Outcome
Title Health-related Quality of Life Using the SF-36 Physical Composite
Hide Description 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.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Plasma Exchange No Plasma Exchange
Hide Arm/Group Description:

Participants in this arm undergo plasma exchange and take take either a standard glucocorticoid dose or a reduced glucocorticoid dose.

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.

Participants in this arm do not undergo plasma exchange and take either a standard glucocorticoid dose or a reduced glucocorticoid dose.

No Plasma Exchange: No plasma exchange.

Overall Number of Participants Analyzed 352 352
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
39.04
(38.58 to 41.65)
37.96
(37.5 to 40.57)
5.Secondary Outcome
Title Health-related Quality of Life Using the SF-36 Mental Composite
Hide Description 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.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Plasma Exchange No Plasma Exchange
Hide Arm/Group Description:

Participants in this arm undergo plasma exchange and take take either a standard glucocorticoid dose or a reduced glucocorticoid dose.

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.

Participants in this arm do not undergo plasma exchange and take either a standard glucocorticoid dose or a reduced glucocorticoid dose.

No Plasma Exchange: No plasma exchange.

Overall Number of Participants Analyzed 352 352
Mean (95% Confidence Interval)
Unit of Measure: score on a scale
51.94
(51.27 to 53.70)
51.40
(50.73 to 53.16)
6.Secondary Outcome
Title Health-related Quality of Life Using the EQ-5D Index Descriptive System
Hide Description 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.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Plasma Exchange No Plasma Exchange
Hide Arm/Group Description:

Participants in this arm undergo plasma exchange and take take either a standard glucocorticoid dose or a reduced glucocorticoid dose.

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.

Participants in this arm do not undergo plasma exchange and take either a standard glucocorticoid dose or a reduced glucocorticoid dose.

No Plasma Exchange: No plasma exchange.

Overall Number of Participants Analyzed 352 352
Mean (95% Confidence Interval)
Unit of Measure: score on a scale
0.79
(0.78 to 0.84)
0.77
(0.76 to 0.82)
Time Frame Adverse event data was collected from time of consent through study completion. The first subject was enrolled in June 2010, and the study completed in July 2017. Adverse event data was collected for 7 years and 1 month.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Plasma Exchange No Plasma Exchange
Hide Arm/Group Description 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. Participants in this arm do not undergo plasma exchange
All-Cause Mortality
Plasma Exchange No Plasma Exchange
Affected / at Risk (%) Affected / at Risk (%)
Total   46/352 (13.07%)   53/352 (15.06%) 
Hide Serious Adverse Events
Plasma Exchange No Plasma Exchange
Affected / at Risk (%) Affected / at Risk (%)
Total   225/352 (63.92%)   224/352 (63.64%) 
Blood and lymphatic system disorders     
Hematological   25/352 (7.10%)  16/352 (4.55%) 
Cardiac disorders     
Cardiovascular   69/352 (19.60%)  55/352 (15.63%) 
Endocrine disorders     
Endocrine   9/352 (2.56%)  2/352 (0.57%) 
Gastrointestinal disorders     
Gastrointestinal   34/352 (9.66%)  39/352 (11.08%) 
General disorders     
Other   89/352 (25.28%)  79/352 (22.44%) 
Immune system disorders     
Vasculitis Relapse   23/352 (6.53%)  32/352 (9.09%) 
Infections and infestations     
Infection   136/352 (38.64%)  114/352 (32.39%) 
Renal and urinary disorders     
Renal   41/352 (11.65%)  36/352 (10.23%) 
Vascular disorders     
Surgery   16/352 (4.55%)  13/352 (3.69%) 
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Plasma Exchange No Plasma Exchange
Affected / at Risk (%) Affected / at Risk (%)
Total   0/352 (0.00%)   0/352 (0.00%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Michael Walsh
Organization: McMaster University, Hamilton, Ontario
Phone: 905-522-1155 ext 34055
EMail: lastwalsh1975@gmail.com
Layout table for additonal information
Responsible Party: Peter Merkel, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00987389    
Obsolete Identifiers: NCT03919825
Other Study ID Numbers: PEXIVAS
R01FD00351604 ( Other Grant/Funding Number: Food and Drug Administration (FDA) )
2009-013220-24 ( EudraCT Number )
First Submitted: September 23, 2009
First Posted: September 30, 2009
Results First Submitted: October 31, 2018
Results First Posted: May 26, 2020
Last Update Posted: May 26, 2020