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

• 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: University of Pennsylvania
• 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

Participant Flow

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
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

Baseline Characteristics

Arm/Group Title		Plasma Exchange	No Plasma Exchange	Total
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
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

Outcome Measures

1. Primary Outcome

Title	Composite of i) All-cause Mortality or ii) End-stage Renal Disease
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Plasma Exchange	No Plasma Exchange
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
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Plasma Exchange	No Plasma Exchange
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
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Plasma Exchange	No Plasma Exchange
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
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Plasma Exchange	No Plasma Exchange
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
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Plasma Exchange	No Plasma Exchange
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
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Plasma Exchange	No Plasma Exchange
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)

Adverse Events

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
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%)
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
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%)

Limitations and Caveats

[Not Specified]

More Information

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

• Name/Title: Dr. Michael Walsh
• Organization: McMaster University, Hamilton, Ontario
• Phone: 905-522-1155 ext 34055
• EMail: lastwalsh1975@gmail.com

Publications of Results:

Walsh M, Merkel PA, Peh CA, Szpirt WM, Puéchal 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-Suárez 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.

Other 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.

• 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