Trial Outcomes & Findings for Plasma Exchange and Glucocorticoids for Treatment of Anti-Neutrophil Cytoplasm Antibody (ANCA) - Associated Vasculitis (NCT NCT00987389)
NCT ID: NCT00987389
Last Updated: 2020-05-26
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
704 participants
Primary outcome timeframe
Time frame varied by subject: minimum of 1 year - maximum of 7 years
Results posted on
2020-05-26
Participant Flow
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.
Participant milestones
| Measure |
Plasma Exchange With Standard Glucocorticoids
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 With Reduced Glucocorticoids
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.
|
No Plasma Exchange With Standard Glucocorticoids
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.
|
No Plasma Exchange With Reduced Glucocorticoid
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.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
176
|
176
|
175
|
177
|
|
Overall Study
COMPLETED
|
167
|
168
|
167
|
174
|
|
Overall Study
NOT COMPLETED
|
9
|
8
|
8
|
3
|
Reasons for withdrawal
| Measure |
Plasma Exchange With Standard Glucocorticoids
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 With Reduced Glucocorticoids
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.
|
No Plasma Exchange With Standard Glucocorticoids
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.
|
No Plasma Exchange With Reduced Glucocorticoid
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.
|
|---|---|---|---|---|
|
Overall Study
Ineligible
|
0
|
3
|
0
|
0
|
|
Overall Study
Lost to Follow-up
|
4
|
1
|
3
|
1
|
|
Overall Study
Withdrawal by Subject
|
4
|
3
|
2
|
1
|
|
Overall Study
Withdrawn from Treatment
|
0
|
1
|
0
|
0
|
|
Overall Study
Multiple different reasons
|
1
|
0
|
3
|
1
|
Baseline Characteristics
Plasma Exchange and Glucocorticoids for Treatment of Anti-Neutrophil Cytoplasm Antibody (ANCA) - Associated Vasculitis
Baseline characteristics by cohort
| Measure |
Plasma Exchange
n=352 Participants
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.
|
No Plasma Exchange
n=352 Participants
Participants in this arm do not undergo plasma exchange.
|
Total
n=704 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62.8 years
STANDARD_DEVIATION 14.4 • n=5 Participants
|
63.5 years
STANDARD_DEVIATION 13.7 • n=7 Participants
|
63.2 years
STANDARD_DEVIATION 14 • n=5 Participants
|
|
Sex: Female, Male
Female
|
149 Participants
n=5 Participants
|
158 Participants
n=7 Participants
|
307 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
203 Participants
n=5 Participants
|
194 Participants
n=7 Participants
|
397 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
South Asian
|
7 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Arab
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Chinese
|
1 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Japanese
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other Asian
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black African
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Coloured African
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other Black
|
5 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
European
|
281 Participants
n=5 Participants
|
277 Participants
n=7 Participants
|
558 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Latin America
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native N/S American or Aborigine
|
16 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
24 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
52 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Missing
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
24 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
|
Region of Enrollment
Czechia
|
7 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Region of Enrollment
Japan
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
88 Participants
n=5 Participants
|
91 Participants
n=7 Participants
|
179 Participants
n=5 Participants
|
|
Region of Enrollment
New Zealand
|
6 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
97 Participants
n=5 Participants
|
94 Participants
n=7 Participants
|
191 Participants
n=5 Participants
|
|
Region of Enrollment
Sweden
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Region of Enrollment
Belgium
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
Norway
|
0 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Region of Enrollment
Denmark
|
25 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
57 Participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
18 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Region of Enrollment
Mexico
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Region of Enrollment
Australia
|
44 Participants
n=5 Participants
|
50 Participants
n=7 Participants
|
94 Participants
n=5 Participants
|
|
Region of Enrollment
France
|
21 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
52 Participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
5 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
ANCA Binding Specificity: PR3
|
143 Participants
n=5 Participants
|
143 Participants
n=7 Participants
|
286 Participants
n=5 Participants
|
|
ANCA Binding Specificity: MPO
|
209 Participants
n=5 Participants
|
209 Participants
n=7 Participants
|
418 Participants
n=5 Participants
|
|
Severity of Renal Disease at Presentation: Creatinine <500umol/min
|
251 Participants
n=5 Participants
|
248 Participants
n=7 Participants
|
499 Participants
n=5 Participants
|
|
Severity of Renal Disease at Presentation: Requiring Dialysis or Creatinine >=500umol/min
|
101 Participants
n=5 Participants
|
104 Participants
n=7 Participants
|
205 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Time frame varied by subject: minimum of 1 year - maximum of 7 yearsThe 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.
Outcome measures
| Measure |
Plasma Exchange
n=352 Participants
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.
|
No Plasma Exchange
n=352 Participants
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.
|
|---|---|---|
|
Composite of i) All-cause Mortality or ii) End-stage Renal Disease
|
100 Participants
|
109 Participants
|
SECONDARY outcome
Timeframe: Time frame varied by subject: minimum of 1 year - maximum of 7 yearsRemission that occurs before 6 months, and lasts without a first relapse until at least 12 months after randomization
Outcome measures
| Measure |
Plasma Exchange
n=352 Participants
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.
|
No Plasma Exchange
n=352 Participants
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.
|
|---|---|---|
|
Number of Participants With Sustained Remission
|
200 Participants
|
197 Participants
|
SECONDARY outcome
Timeframe: Time frame varied by subject: minimum of 1 year - maximum of 7 yearsSerious infections defined as an infectious syndrome that requires intravenous antibiotics or hospitalization for treatment.
Outcome measures
| Measure |
Plasma Exchange
n=352 Participants
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.
|
No Plasma Exchange
n=352 Participants
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.
|
|---|---|---|
|
Rate of Serious Infection Events
|
145 events
|
132 events
|
SECONDARY outcome
Timeframe: 12 monthsQuality 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.
Outcome measures
| Measure |
Plasma Exchange
n=352 Participants
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.
|
No Plasma Exchange
n=352 Participants
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.
|
|---|---|---|
|
Health-related Quality of Life Using the SF-36 Physical Composite
|
39.04 units on a scale
Interval 38.58 to 41.65
|
37.96 units on a scale
Interval 37.5 to 40.57
|
SECONDARY outcome
Timeframe: 12 monthsQuality 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.
Outcome measures
| Measure |
Plasma Exchange
n=352 Participants
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.
|
No Plasma Exchange
n=352 Participants
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.
|
|---|---|---|
|
Health-related Quality of Life Using the SF-36 Mental Composite
|
51.94 score on a scale
Interval 51.27 to 53.7
|
51.40 score on a scale
Interval 50.73 to 53.16
|
SECONDARY outcome
Timeframe: 12 monthsEuroQoL-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.
Outcome measures
| Measure |
Plasma Exchange
n=352 Participants
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.
|
No Plasma Exchange
n=352 Participants
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.
|
|---|---|---|
|
Health-related Quality of Life Using the EQ-5D Index Descriptive System
|
0.79 score on a scale
Interval 0.78 to 0.84
|
0.77 score on a scale
Interval 0.76 to 0.82
|
Adverse Events
Plasma Exchange
Serious events: 225 serious events
Other events: 0 other events
Deaths: 46 deaths
No Plasma Exchange
Serious events: 224 serious events
Other events: 0 other events
Deaths: 53 deaths
Serious adverse events
| Measure |
Plasma Exchange
n=352 participants at risk
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.
|
No Plasma Exchange
n=352 participants at risk
Participants in this arm do not undergo plasma exchange
|
|---|---|---|
|
Cardiac disorders
Cardiovascular
|
19.6%
69/352 • 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.
|
15.6%
55/352 • 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.
|
|
Endocrine disorders
Endocrine
|
2.6%
9/352 • 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.
|
0.57%
2/352 • 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.
|
|
Gastrointestinal disorders
Gastrointestinal
|
9.7%
34/352 • 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.
|
11.1%
39/352 • 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.
|
|
Blood and lymphatic system disorders
Hematological
|
7.1%
25/352 • 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.
|
4.5%
16/352 • 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.
|
|
Infections and infestations
Infection
|
38.6%
136/352 • 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.
|
32.4%
114/352 • 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.
|
|
Renal and urinary disorders
Renal
|
11.6%
41/352 • 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.
|
10.2%
36/352 • 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.
|
|
Vascular disorders
Surgery
|
4.5%
16/352 • 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.
|
3.7%
13/352 • 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.
|
|
Immune system disorders
Vasculitis Relapse
|
6.5%
23/352 • 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.
|
9.1%
32/352 • 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.
|
|
General disorders
Other
|
25.3%
89/352 • 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.
|
22.4%
79/352 • 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.
|
Other adverse events
Adverse event data not reported
Additional Information
Dr. Michael Walsh
McMaster University, Hamilton, Ontario
Phone: 905-522-1155
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place