A Randomized Multicenter Study for Isolated Skin Vasculitis

NCT ID: NCT02939573

Last Updated: 2026-01-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-01-01

Study Completion Date

2028-12-31

Brief Summary

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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

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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.

Conditions

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Primary Cutaneous Vasculitis Cutaneous Polyarteritis Nodosa IgA Vasculitis Henoch-Schönlein Purpura

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Stage 1

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).

Group Type EXPERIMENTAL

Colchicine

Intervention Type DRUG

Randomized to colchicine 0.6 mg x 2/day

Dapsone

Intervention Type DRUG

Randomized to dapsone 150 mg/day

Azathioprine

Intervention Type DRUG

Randomized to azathioprine 2 mg/kg/day

Stage 2

If the patient has to discontinue the study drug within the (stage 1) 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, colchicine 0.6 mg x 2/day; dapsone 150 mg/day; azathioprine 2 mg/kg/day) for 6 months. Endpoint in this second stage will again be the response to treatment at 6 months.

Group Type EXPERIMENTAL

Colchicine

Intervention Type DRUG

Randomized to colchicine 0.6 mg x 2/day

Dapsone

Intervention Type DRUG

Randomized to dapsone 150 mg/day

Azathioprine

Intervention Type DRUG

Randomized to azathioprine 2 mg/kg/day

Interventions

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Colchicine

Randomized to colchicine 0.6 mg x 2/day

Intervention Type DRUG

Dapsone

Randomized to dapsone 150 mg/day

Intervention Type DRUG

Azathioprine

Randomized to azathioprine 2 mg/kg/day

Intervention Type DRUG

Other Intervention Names

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Colcrys DDS Diaminodiphenylsulfone Imuran

Eligibility Criteria

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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

2. Known systemic and/or non-skin-isolated vasculitis, such as granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, cryoglobulinemic vasculitis, systemic polyarteritis nodosa, central nervous system vasculitis and patients with detectable antineutrophil cytoplasmic antibody (ANCA) by immunofluorescence or ELISA.
3. Hypocomplementemic urticarial vasculitis, cryoglobulinemic vasculitis, and other known secondary skin vasculitides such as those secondary to systemic lupus erythematosus, Sjögren syndrome, another auto-immune condition, a cancer, a hematological disorder, an ongoing active infection, or an ongoing medication. Investigators should consider such underlying diagnoses and perform and interpret appropriate laboratory work-up where indicated based on clinical presentation.
4. History of significant intolerance, allergy or serious adverse events to any of the study medications: 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 patients enrolled directly in stage 2 of the study will be capped at 10 (10%).
5. Patients who have contra-indications to two or three of the study drugs (azathioprine, colchicine, or dapsone), or have been treated prior to enrollment with two or three of the study drugs but failed to respond to them, or had to stop two or three of them because of adverse events.
6. Deficit in glucose-6-phosphate dehydrogenase (G6PD) or history of hemolytic anemia (all patients must be tested for G6PD at the screening visit to assess for their eligibility): 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 (azathioprine or colchicine). The number of patients enrolled directly in stage 2 of the study will be capped at 10 (10%).
7. Low or absent thiopurine methyltransferase (TPMT) activity (if known, not a requirement for study entry): Patients known to have low or absent TPMT can be enrolled directly in the second stage of the study and be randomized to receive one of the two other study drugs (dapsone or colchicine).
8. Evidence of significant hepatic insufficiency or liver function tests \> 2 times the upper limit of normal.
9. Evidence of significant renal insufficiency or creatinine clearance \< 60 mL/min.
10. Evidence of significant or symptomatic anemia or Hb \< 10 g/dL.
11. Comorbid condition that has moderate or high likelihood of requiring intermittent courses of prednisone within the study period, according to the investigator (e.g. chronic obstructive pulmonary disease (COPD), unstable or severe asthma).
12. Active cancer or history of malignancy within the previous 5 years (patient in remission of a cancer \>5 years, or with non-metastatic prostate cancer or treated basal or squamous cell carcinoma of the skin can be enrolled).
13. Active uncontrolled or serious infection that may compromise or contra-indicate the use of the study medications.
14. Patient unable to consent.
15. Pregnant or lactating women.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIH

Sponsor Role collaborator

National Center for Advancing Translational Sciences (NCATS)

NIH

Sponsor Role collaborator

Office of Rare Diseases (ORD)

NIH

Sponsor Role collaborator

University of Pennsylvania

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Robert Micheletti, MD

Role: STUDY_CHAIR

University of Pennsylvania

Christian Pagnoux, MD, MPH, MSc

Role: STUDY_CHAIR

University of Toronto/Mount Sinai Hospital

Locations

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University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status RECRUITING

Boston University School of Medicine

Boston, Massachusetts, United States

Site Status COMPLETED

Mayo Clinic

Rochester, Minnesota, United States

Site Status COMPLETED

Northwell Health

Lake Success, New York, United States

Site Status COMPLETED

Hospital for Special Surgery

New York, New York, United States

Site Status COMPLETED

Cleveland Clinic

Cleveland, Ohio, United States

Site Status COMPLETED

Penn State Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status COMPLETED

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Vanderbilt University

Nashville, Tennessee, United States

Site Status RECRUITING

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status RECRUITING

University of Utah

Salt Lake City, Utah, United States

Site Status COMPLETED

University of Virginia

Charlottesville, Virginia, United States

Site Status RECRUITING

St. Joseph's Healthcare

Hamilton, Ontario, Canada

Site Status RECRUITING

University of Toronto Mount Sinai Hospital

Toronto, Ontario, Canada

Site Status RECRUITING

McGill University Health Centre

Montreal, Quebec, Canada

Site Status RECRUITING

Tohoku Medical and Pharmaceutical University Hospital

Kyoto, , Japan

Site Status COMPLETED

Countries

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United States Canada Japan

Central Contacts

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Carol McAlear, MA

Role: CONTACT

Facility Contacts

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Theresa Howard

Role: primary

Laura Cesar

Role: primary

Pamela Schlairet

Role: primary

Aleuna Lee

Role: primary

Lauren Kuhns

Role: primary

Sandra Messier

Role: primary

Nazrana Haq

Role: primary

Michele Tobaly

Role: primary

References

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Hahn D, Hodson EM, Craig JC. Interventions for preventing and treating kidney disease in IgA vasculitis. Cochrane Database Syst Rev. 2023 Feb 28;2(2):CD005128. doi: 10.1002/14651858.CD005128.pub4.

Reference Type DERIVED
PMID: 36853224 (View on PubMed)

Micheletti RG, Pagnoux C, Tamura RN, Grayson PC, McAlear CA, Borchin R, Krischer JP, Merkel PA; Vasculitis Clinical Research Consortium. Protocol for a randomized multicenter study for isolated skin vasculitis (ARAMIS) comparing the efficacy of three drugs: azathioprine, colchicine, and dapsone. Trials. 2020 Apr 28;21(1):362. doi: 10.1186/s13063-020-04285-3.

Reference Type DERIVED
PMID: 32345372 (View on PubMed)

Related Links

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http://www.rarediseasesnetwork.org/vcrc

Vasculitis Clinical Research Consoritum

Other Identifiers

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U54AR057319

Identifier Type: NIH

Identifier Source: secondary_id

View Link

VCRC5562

Identifier Type: -

Identifier Source: org_study_id

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