A Randomized Multicenter Study for Isolated Skin Vasculitis (ARAMIS)

January 30, 2024 updated by: University of Pennsylvania
Multi-center sequential multiple assignment randomized trial comparing the effectiveness of three different standard of care treatment options for patients with isolated skin vasculitis.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

90

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
    • Ontario
      • Hamilton, Ontario, Canada
      • Toronto, Ontario, Canada
    • Quebec
  • Japan
      • Kyoto, Japan, 602-8566
        • Completed
        • Tohoku Medical and Pharmaceutical University Hospital
  • United States
    • Kansas
      • Kansas City, Kansas, United States
        • Recruiting
        • University of Kansas Medical Center
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Completed
        • Boston University School of Medicine
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Completed
        • Mayo Clinic
    • New York
      • Lake Success, New York, United States, 11042
        • Completed
        • Northwell Health
      • New York, New York, United States, 10021
        • Completed
        • Hospital for Special Surgery
    • Ohio
      • Cleveland, Ohio, United States
        • Completed
        • Cleveland Clinic
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Completed
        • Penn State Hershey Medical Center
      • Philadelphia, Pennsylvania, United States, 19104
    • Tennessee
      • Nashville, Tennessee, United States, 37232
    • Texas
    • Utah
      • Salt Lake City, Utah, United States
        • Completed
        • University of Utah
    • Virginia
      • Charlottesville, Virginia, United States, 22903

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 exclusion criteria. Mild and stable microscopic hematuria without RBC casts and/or mild and stable proteinuria (<1g/24 hours) are not exclusion criteria. These latter patients must not require systemic immunosuppressive therapy because of possible renal involvement and their GFR must be >60 ml/min.
  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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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).
Drug: Colchicine
Randomized to colchicine 0.6 mg x 2/day
Other Names:
  • Colcrys
Drug: Dapsone
Randomized to dapsone 150 mg/day
Other Names:
  • DDS
  • Diaminodiphenylsulfone
Drug: Azathioprine
Randomized to azathioprine 2 mg/kg/day
Other Names:
  • Imuran
Experimental: 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.
Drug: Colchicine
Randomized to colchicine 0.6 mg x 2/day
Other Names:
  • Colcrys
Drug: Dapsone
Randomized to dapsone 150 mg/day
Other Names:
  • DDS
  • Diaminodiphenylsulfone
Drug: Azathioprine
Randomized to azathioprine 2 mg/kg/day
Other Names:
  • Imuran

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy of the study drugs for the treatment of skin vasculitis.
Time Frame: Response to therapy at month 6 of the pooled study stages 1 and 2.
Compare response to therapies.
Response to therapy at month 6 of the pooled study stages 1 and 2.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response rates for each of the study drugs
Time Frame: Response evaluated months 3, 6 and 12
Proportion of patient with complete response and significant response to therapy at months 3, 6 and 12
Response evaluated months 3, 6 and 12
Physician's global assessment of response
Time Frame: Assessed at months 0, 1, 3, 6, 9, and 12.
Health-related quality of life as measured using physician's global assessment scale.
Assessed at months 0, 1, 3, 6, 9, and 12.
Patient's global assessment of response
Time Frame: Assessed at months 0, 1, 3, 6, 9, and 12.
Health-related quality of life as measured using patient's global assessment scale.
Assessed at months 0, 1, 3, 6, 9, and 12.
Skindex29 score
Time Frame: Assessed at months 1, 3, 6, 9, and 12.
Disease activity measured by response to therapy at months 1, 3, 6, and 12
Assessed at months 1, 3, 6, 9, and 12.
Health-related quality of life
Time Frame: 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)
Assessed at months 1, 3, 6, 9, and 12.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pennsylvania

Collaborators

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Center for Advancing Translational Sciences (NCATS)
Office of Rare Diseases (ORD)

Investigators

  • Study Chair: Robert Micheletti, MD, University of Pennsylvania
  • Study Chair: Christian Pagnoux, MD, MPH, MSc, University of Toronto/Mount Sinai Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2017

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

October 18, 2016

First Submitted That Met QC Criteria

October 18, 2016

First Posted (Estimated)

October 20, 2016

Study Record Updates

Last Update Posted (Actual)

February 1, 2024

Last Update Submitted That Met QC Criteria

January 30, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VCRC5562
  • U54AR057319 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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