A Phase 3 interventional study of Plasma Exchange and No Plasma Exchange in Granulomatosis With Polyangiitis (Wegener's) (GPA) and Microscopic Polyangiitis (MPA), sponsored by University of Pennsylvania. Completed at 98 sites in 15 countries. Open to participants aged 15 Years and older. Per ClinicalTrials.gov, last updated 2020-05-26.
Sponsored by University of Pennsylvania · Phase 3, Interventional, and Treatment
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.
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;
All studies will receive standard remission-induction therapy with either cyclophosphamide or rituximab.
104 studies on the registry are indexed under Granulomatosis with Polyangiitis; 16 are open to participants now.
This study's enrollment of 704 is above the median of 70 across 69 interventional studies indexed under Granulomatosis with Polyangiitis.
Browse Granulomatosis with Polyangiitis studies →University of Pennsylvania is the lead sponsor of 1,668 studies on the registry; 235 are open to participants now.
Of its 158 completed or terminated interventional studies of FDA-regulated products, 109 (69%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
AND
AND
Severe vasculitis defined by at least one of the following:
Renal involvement characterized by both of the following:
AND
Pulmonary hemorrhage due to active vasculitis defined by:
AND
AND
At least one of the following:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants in this arm undergo plasma exchange and take a standard glucocorticoid dose.
Procedure: Plasma Exchange · Drug: Glucocorticoids [Standard Dose]
Participants in this arm do not undergo plasma exchange and take a standard glucocorticoid dose.
Other: No Plasma Exchange · Drug: Glucocorticoids [Standard Dose]
Participants in this arm undergo plasma exchange and take a reduced glucocorticoid dose.
Procedure: Plasma Exchange · Drug: Glucocorticoids [Reduced Dose]
Participants in this arm do not undergo plasma exchange and take a reduced glucocorticoid dose.
Other: No Plasma Exchange · Drug: Glucocorticoids [Reduced Dose]
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.
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.
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.
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.
Time frame: Time frame varied by subject: minimum of 1 year - maximum of 7 years
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
Time frame: 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.
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
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
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.
Time frame: 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.
Time frame: 12 months
| Milestone | Plasma Exchange With Standard Glucocorticoids | Plasma Exchange With Reduced Glucocorticoids | No Plasma Exchange With Standard Glucocorticoids | No Plasma Exchange With Reduced Glucocorticoid |
|---|---|---|---|---|
| Started | 176 | 176 | 175 | 177 |
| Completed | 167 | 168 | 167 | 174 |
| Not completed | 9 | 8 | 8 | 3 |
| Withdrew: Ineligible | 0 | 3 | 0 | 0 |
| Withdrew: Lost to follow-up | 4 | 1 | 3 | 1 |
| Withdrew: Withdrawal by subject | 4 | 3 | 2 | 1 |
| Withdrew: Withdrawn from treatment | 0 | 1 | 0 | 0 |
| Withdrew: Multiple different reasons | 1 | 0 | 3 | 1 |
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.
| Participants | Plasma Exchange | No Plasma Exchange |
|---|---|---|
| Composite of i) All-cause Mortality or ii) End-stage Renal Disease | 100 | 109 |
Remission that occurs before 6 months, and lasts without a first relapse until at least 12 months after randomization
| Participants | Plasma Exchange | No Plasma Exchange |
|---|---|---|
| Number of Participants With Sustained Remission | 200 | 197 |
Serious infections defined as an infectious syndrome that requires intravenous antibiotics or hospitalization for treatment.
| events | Plasma Exchange | No Plasma Exchange |
|---|---|---|
| Rate of Serious Infection Events | 145 | 132 |
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.
| units on a scale | Plasma Exchange | No Plasma Exchange |
|---|---|---|
| Health-related Quality of Life Using the SF-36 Physical Composite | 39.04 (38.58 to 41.65) | 37.96 (37.5 to 40.57) |
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.
| score on a scale | Plasma Exchange | No Plasma Exchange |
|---|---|---|
| Health-related Quality of Life Using the SF-36 Mental Composite | 51.94 (51.27 to 53.70) | 51.40 (50.73 to 53.16) |
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.
| score on a scale | Plasma Exchange | No Plasma Exchange |
|---|---|---|
| Health-related Quality of Life Using the EQ-5D Index Descriptive System | 0.79 (0.78 to 0.84) | 0.77 (0.76 to 0.82) |
Collected over 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.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Plasma Exchange | 46/352 (13.1%) | 225/352 (63.9%) | 0/352 (0%) |
| No Plasma Exchange | 53/352 (15.1%) | 224/352 (63.6%) | 0/352 (0%) |
| Event | Plasma Exchange | No Plasma Exchange |
|---|---|---|
| InfectionInfections and infestations | 136/352 | 114/352 |
| OtherGeneral disorders | 89/352 | 79/352 |
| CardiovascularCardiac disorders | 69/352 | 55/352 |
| RenalRenal and urinary disorders | 41/352 | 36/352 |
| GastrointestinalGastrointestinal disorders | 34/352 | 39/352 |
| Vasculitis RelapseImmune system disorders | 23/352 | 32/352 |
| HematologicalBlood and lymphatic system disorders | 25/352 | 16/352 |
| SurgeryVascular disorders | 16/352 | 13/352 |
| EndocrineEndocrine disorders | 9/352 | 2/352 |
| Age, Continuous(years) | Plasma Exchange | No Plasma Exchange | Total |
|---|---|---|---|
| Mean | 62.8 ± 14.4 | 63.5 ± 13.7 | 63.2 ± 14 |
| Sex: Female, Male(Participants) | Plasma Exchange | No Plasma Exchange | Total |
|---|---|---|---|
| Female | 149 | 158 | 307 |
| Male | 203 | 194 | 397 |
| Race/Ethnicity, Customized(Participants) | Plasma Exchange | No Plasma Exchange | Total |
|---|---|---|---|
| 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(Participants) | Plasma Exchange | No Plasma Exchange | Total |
|---|---|---|---|
| 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(Participants) | Plasma Exchange | No Plasma Exchange | Total |
|---|---|---|---|
| Count of participants | 143 | 143 | 286 |
| ANCA Binding Specificity: MPO(Participants) | Plasma Exchange | No Plasma Exchange | Total |
|---|---|---|---|
| Count of participants | 209 | 209 | 418 |
| Severity of Renal Disease at Presentation: Creatinine <500umol/min(Participants) | Plasma Exchange | No Plasma Exchange | Total |
|---|---|---|---|
| Count of participants | 251 | 248 | 499 |
| Severity of Renal Disease at Presentation: Requiring Dialysis or Creatinine >=500umol/min(Participants) | Plasma Exchange | No Plasma Exchange | Total |
|---|---|---|---|
| Count of participants | 101 | 104 | 205 |
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from May 2010 to primary completion in Aug 2017, 87 months.
Results were first posted in May 2020, 2 years 9 months after primary completion.
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Studies of the drug tested here: Corticosteroids
Granulomatosis with Polyangiitis →