Cutaneous Polyarteritis Nodosa, Henoch-Schönlein Purpura, IgA Vasculitis, Primary Cutaneous Vasculitis
Conditions
Brief summary
Multi-center sequential multiple assignment randomized trial comparing the effectiveness of three different standard of care treatment options for patients with isolated skin vasculitis.
Detailed description
Eligible patients will be initially randomized (1:1:1) to receive one of the 3 medications under investigation (colchicine 0.6 mg x 2/day; dapsone 150 mg/day; azathioprine 2 mg/kg/day) for 6 months. Endpoint is response to treatment at month 6 (stage 1). If the patient has to discontinue the study drug within the 6 month study period or during the subsequent follow-up period (up to month 12) because of a lack of response (or failure), flare or side effect, he/she will be randomized again to receive one of the remaining two study drugs (stage 2, with a 1:1 randomization ratio) for 6 months. Endpoint in this second stage will again be the response to treatment at 6 months.
Interventions
DRUGColchicine
Randomized to colchicine 0.6 mg x 2/day
DRUGDapsone
Randomized to dapsone 150 mg/day
DRUGAzathioprine
Randomized to azathioprine 2 mg/kg/day
Sponsors
University of Pennsylvania
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Center for Advancing Translational Sciences (NCATS)
Office of Rare Diseases (ORD)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with primary skin vasculitis, not associated with any significant extra-cutaneous involvement that would require specific immunosuppressive therapy. Eligible patients will have a diagnosis of either: * Isolated cutaneous small vessel (SV) or medium-sized vessel (MV) vasculitis or cutaneous polyarteritis nodosa (PAN) * IgA vasculitis (IgA, formerly Henoch-Schönlein purpura), without active and/or progressing renal involvement (stable glomerular filtration rate (GFR) \>60 ml/min; absence of, or mild-and-stable microscopic hematuria without red blood cell casts; absence of, or mild-and-stable proteinuria (\<1g/24 hours); not requiring systemic immunosuppressive therapy). These conditions, when skin-limited, are all currently treated in similar manners in practice. Mild arthralgias, myalgias, peripheral limb edema, fatigue, weight loss ≤6 lbs or 3 kg within past 3 months, low-grade fever, and mild anemia (Hb ≥ 10 g/dL) will be allowed. 2. The diagnosis of vasculitis must have been confirmed by skin biopsy prior to enrollment (earlier, at diagnosis, and/or just prior to enrollment) that has included an immunofluorescence study (in the case of small vessel vasculitis). 3. Patients must have active cutaneous vasculitis lasting for at least 1 month continuously and/or have had 2 or more flares over the six months preceding enrollment (post-inflammatory lesions such as hyperpigmentation or healing ulceration(s) are not to be considered active vasculitis). 4. Patients must have active / ongoing cutaneous vasculitis lesions at the time of enrollment (post-inflammatory lesions such as hyperpigmentation or healing ulceration(s) are not to be considered active vasculitis). 5. Patients may have a contra-indication to one of the study drug or have been treated prior to enrollment with one of the study medications but failed to respond to it (according to the study definitions of failure and if they have been on the drug at the target dose or higher for 3 months or longer) or had to stop it because of an adverse event. Such patients can be enrolled directly in the second stage of the study and be randomized to receive one of the two other study drugs. The number of such patients enrolled directly in stage 2 will be capped at 10 (10% of the total recruitment target). 6. Patients may have received systemic glucocorticoids for their cutaneous vasculitis before enrollment. For the patients on prednisone at the time of enrollment, prednisone should be stopped within a maximum of 6 weeks after enrollment and initiation of the study drug, following a pre-defined tapering schedule. Patients on long-term, low and stable dose of glucocorticoids (≤5 mg/day prednisone-equivalent) for other conditions (e.g., asthma or adrenal insufficiency) can be enrolled if the likelihood of requiring a dose increase for this other condition is low during the 6 month study period (these patients will remain on that low and stable dose during the study period, with the option to receive one short course of prednisone at higher doses for skin vasculitis flare during the first 3 months of the study period, like any other patients enrolled). 7. Participant age 18 years or greater.
Exclusion criteria
1. Presence of significant extra-cutaneous manifestations suggestive of a systemic vasculitis or more diffuse condition. The presence of mild arthralgias, myalgias, peripheral limb edema, fatigue, weight loss ≤6 lbs or 3 kg within past 3 months, low-grade fever, and mild anemia \[Hb ≥ 10 g/dL\] are not
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of the study drugs for the treatment of skin vasculitis. | Response to therapy at month 6 of the pooled study stages 1 and 2. | Compare response to therapies. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Health-related quality of life | Assessed at months 1, 3, 6, 9, and 12. | Health-related quality of life as measured using SF-36 and Patient-Reported Outcomes Measurement Information System (PROMIS) |
| Patient's global assessment of response | Assessed at months 0, 1, 3, 6, 9, and 12. | Health-related quality of life as measured using patient's global assessment scale. |
| Response rates for each of the study drugs | Response evaluated months 3, 6 and 12 | Proportion of patient with complete response and significant response to therapy at months 3, 6 and 12 |
| Physician's global assessment of response | Assessed at months 0, 1, 3, 6, 9, and 12. | Health-related quality of life as measured using physician's global assessment scale. |
| Skindex29 score | Assessed at months 1, 3, 6, 9, and 12. | Disease activity measured by response to therapy at months 1, 3, 6, and 12 |
Countries
Canada, Japan, United States
Contacts
CONTACTCarol McAlear, MA
STUDY_CHAIRRobert Micheletti, MD
University of Pennsylvania
STUDY_CHAIRChristian Pagnoux, MD, MPH, MSc
University of Toronto/Mount Sinai Hospital
Outcome results
None listed