Granulomatosis With Polyangiitis
Conditions
Keywords
Granulomatosis with polyangiitis, Wegener's granulomatosis, WG, GPA, ANCA-Associated Vasculitis, AAV, Vasculitis, Prednisone, Glucocorticoid, Taper
Brief summary
This study is a multi-center randomized controlled trial to evaluate the effects of using low-dose prednisone as compared to stopping prednisone treatment entirely. Participants will be randomized 1:1 to taper their prednisone dose down to 5 mg/day or to 0 mg/day for the duration of the study (approximately six months) or until a study endpoint.
Detailed description
Patients with granulomatosis with polyangiitis (GPA, Wegener's) will be recruited at one of the Vasculitis Centers of Excellence. Participants will be randomized 1:1 either to taper their prednisone dose down to 5 mg/day according to a standardized schedule and stay at 5 mg/day of prednisone for the duration of the study or until a study endpoint, or taper their prednisone dose down to 0 mg/day using a standard schedule and stay at 0 mg/day for the duration of the study or until a study endpoint. All study participants will be followed for 6 months (from reaching a prednisone dose of 5 mg/day) or until an increase of prednisone dose (after randomization) occurs, whichever comes first. Participants will have up to four study visits, a screening visit (visit 1), a baseline (visit 2), a month 3 visit (visit 3) and a month 6 or flare visit (visit 3) and up to two follow-up phone calls from the study coordinator at randomization and at month 1 (randomization and 1 month phone call may be combined if randomization occurs at month 1). This study is a project of the Vasculitis Clinical Research Consortium (VCRC) funded through the National Institutes of Health Rare Diseases Clinical Research Network (RDCRN) with the purpose of promoting vasculitis research. The VCRC is the major clinical research infrastructure in North America for the study of vasculitis, and eight VCRC Centers of Excellence will be recruiting for this study.
Interventions
DRUG5 mg Prednisone
Subjects will remain on daily prednisone dose of 5 mg
DRUG0 mg Prednisone
Subjects will taper their prednisone dose from 5 mg per day to 0 mg per day
Sponsors
University of Pennsylvania
National Heart, Lung, and Blood Institute (NHLBI)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Office of Rare Diseases (ORD)
National Center for Advancing Translational Sciences (NCATS)
Rare Diseases Clinical Research Network
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Established diagnosis of granulomatosis with polyangiitis (GPA) where patients will need to meet at least 2 of the 5 for the classification of GPA, at least one of which must be criterion d or e: The modified American College of Rheumatology (ACR) criteria are: A. Nasal or oral inflammation, defined as the development of painful or painless oral ulcers or purulent or bloody nasal discharge. B. Abnormal chest radiograph, defined as the presence of nodules, fixed infiltrates, or cavities. C. Active urinary sediment, defined as microscopic hematuria (\>5 red blood cells per high power field) or red blood cell casts. D. Granulomatosis inflammation on biopsy, defined as histologic changes showing granulomatous inflammation within the wall of an artery or in the perivascular or extravascular area. Note: Pauci-immune glomerulonephritis seen on kidney biopsy will suffice for this criterion. E. Positive anti-neutrophil cytoplasmic antibody (ANCA) test specific for proteinase-3 measures by enzyme-linked immunoassay. Patients who are myeloperoxidase (MPO) positive or ANCA negative are still eligible for this study if they meet the criteria above and are felt to have GPA. 2. Active disease within the prior 12 months (initial presentation or relapse) that at time of active disease required treatment with prednisone \>20 mg/day. 3. Disease remission at time of enrollment. 4. Prednisone dose at time of enrollment of ≥ 5 mg/day and ≤ 20 mg/day. 5. Participant age of 18 years or greater. 6. If the patient is taking an immunosuppressive medication agent other than prednisone (maintenance agent) then the maintenance agent must be at a stable dose for one month prior to enrollment with no plans by the treating physician to change the dose (other than for safety purposes/toxicity) for the duration of the study (through the month 6 visit or early termination). Acceptable maintenance agents include azathioprine, leflunomide, 6-mercaptopurine, methotrexate, mycophenolate mofetil, mycophenolate sodium, or rituximab. Patients may be on trimethoprim/sulfamethoxazole (TMP/SMX) for use as either a maintenance agent or for prophylaxis for infection. TMP/SMX may be used in combination with other drugs. 6.1 If the patient is regularly taking trimethoprim/sulfamethoxazole at any dose then the patient is eligible if there no plans by the treating physician to change the dose after enrollment (other than dose reduction or discontinuation for safety purposes/toxicity) for the duration of the study.
Exclusion criteria
1\. Comorbid condition that has moderate likelihood of requiring a course of prednisone within one year of enrollment (e.g. chronic obstructive pulmonary disease (COPD), asthma, adrenal insufficiency).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prednisone Dose Increase for Disease Relapse | 6 months | Number of participants who's dose of prednisone was increased due to relapse of the GPA |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rates of Disease Flare Sub Types | 6 months | Rates of GPA disease flare sub types: severe versus non-severe |
| Safety Outcomes. | 6 months | Number of serious adverse events during the study. |
| Protocol Performance at VCRC Centers of Excellence. | 6 months | Evaluation of data completeness between randomized groups from day 0 through the end of the study. |
Countries
Canada, United States
Contacts
PRINCIPAL_INVESTIGATORPeter A Merkel, MD, MPH
University of Pennsylvania
PRINCIPAL_INVESTIGATORJeffery P Krischer, PhD
University of South Florida
Participant flow
Pre-assignment details
Of 159 enrolled participants, 143 met the criteria for randomisation and were randomised 1:1 per protocol.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 58.4 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 65 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 10 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 126 Participants |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 71 | 0 / 72 |
| other Total, other adverse events | 6 / 71 | 3 / 72 |
| serious Total, serious adverse events | 1 / 71 | 1 / 72 |
Outcome results
None listed