A Randomized Multicenter Study for Isolated Skin Vasculitis

NCT02939573 | Recruiting Phase 2 DMC

• 2 other identifiers: VCRC5562U54AR057319
• Study Type: interventional
• Target: 90
• Locations: 3 countries
• Sites: 16

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Efficacy of the study drugs for the treatment of skin vasculitis.

  Compare response to therapies.

  Response to therapy at month 6 of the pooled study stages 1 and 2.

Secondary Outcomes (5)

• Response rates for each of the study drugs

  Response evaluated months 3, 6 and 12

• Physician's global assessment of response

  Assessed at months 0, 1, 3, 6, 9, and 12.

• Patient's global assessment of response

  Assessed at months 0, 1, 3, 6, 9, and 12.

• Skindex29 score

  Assessed at months 1, 3, 6, 9, and 12.

• Health-related quality of life

  Assessed at months 1, 3, 6, 9, and 12.

Study Arms (2)

Stage 1

EXPERIMENTAL

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).

Drug: Colchicine; Drug: Dapsone; Drug: Azathioprine

Stage 2

EXPERIMENTAL

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.

Drug: Colchicine; Drug: Dapsone; Drug: Azathioprine

Interventions

Colchicine DRUG

Randomized to colchicine 0.6 mg x 2/day

Also known as: Colcrys

Stage 1; Stage 2

Dapsone DRUG

Randomized to dapsone 150 mg/day

Also known as: DDS, Diaminodiphenylsulfone

Stage 1; Stage 2

Azathioprine DRUG

Randomized to azathioprine 2 mg/kg/day

Also known as: Imuran

Stage 1; Stage 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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).
• 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).
• 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).
• 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).
• 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).
• Participant age 18 years or greater.

You may not qualify if:

• 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.
• 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.
• 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%).
• 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.
• 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%).
• 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).
• Evidence of significant hepatic insufficiency or liver function tests \> 2 times the upper limit of normal.
• Evidence of significant renal insufficiency or creatinine clearance \< 60 mL/min.
• Evidence of significant or symptomatic anemia or Hb \< 10 g/dL.
• 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).
• 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).
• Active uncontrolled or serious infection that may compromise or contra-indicate the use of the study medications.
• Patient unable to consent.
• Pregnant or lactating women.

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator
• National Center for Advancing Translational Sciences (NCATS): collaborator
• Office of Rare Diseases (ORD): collaborator

Study Sites (16)

University of Kansas Medical Center

Kansas City, Kansas, United States

RECRUITING

Boston University School of Medicine

Boston, Massachusetts, 02118, United States

COMPLETED

Mayo Clinic

Rochester, Minnesota, 55905, United States

COMPLETED

Northwell Health

Lake Success, New York, 11042, United States

COMPLETED

Hospital for Special Surgery

New York, New York, 10021, United States

COMPLETED

Cleveland Clinic

Cleveland, Ohio, United States

COMPLETED

Penn State Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

COMPLETED

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Vanderbilt University

Nashville, Tennessee, 37232, United States

RECRUITING

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

University of Utah

Salt Lake City, Utah, United States

COMPLETED

University of Virginia

Charlottesville, Virginia, 22903, United States

RECRUITING

St. Joseph's Healthcare

Hamilton, Ontario, Canada

RECRUITING

University of Toronto Mount Sinai Hospital

Toronto, Ontario, Canada

RECRUITING

McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

Tohoku Medical and Pharmaceutical University Hospital

Kyoto, 602-8566, Japan

COMPLETED

Related Publications (2)

• 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.

  PMID: 36853224 DERIVED

• 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.

  PMID: 32345372 DERIVED

Related Links

• Vasculitis Clinical Research Consoritum

MeSH Terms

Conditions

IgA Vasculitis

Interventions

Colchicine; Dapsone; Azathioprine

Condition Hierarchy (Ancestors)

Vasculitis; Vascular Diseases; Cardiovascular Diseases; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemostatic Disorders; Hemorrhagic Disorders; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Immune Complex Diseases; Hypersensitivity; Immune System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds; Sulfones; Sulfur Compounds; Organic Chemicals; Thionucleosides; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Robert Micheletti, MD

  University of Pennsylvania

  STUDY CHAIR

• Christian Pagnoux, MD, MPH, MSc

  University of Toronto/Mount Sinai Hospital

  STUDY CHAIR

Central Study Contacts

Carol McAlear, MA

CONTACT

cmcalear@upenn.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2016
• First Posted: October 20, 2016
• Study Start: January 1, 2017
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: January 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (12); JP (1); CA (3)