5562: A randomized multicenter study for isolated skin vasculitis (ARAMIS)

The purpose of this study is to evaluate different treatment options for patients with skin vasculitis (also called cutaneous vasculitis). Patients with small- or medium-vessel vasculitis that only involves the skin ("isolated skin vasculitis"), including some forms of polyarteritis nodosa or IgA vasculitis (Henoch-Schönlein purpura) can join this study. There is not a common preferred or recommended treatment option for isolated skin vasculitis, and different doctors may advise using different drugs, based only on their personal experience. The most frequently used treatments for skin vasculitis are colchicine, dapsone and azathioprine. This study will compare how effective these three drugs are at treating isolated cutaneous vasculitis.

For Diseases

• Isolated cutaneous small-vessel (SVV)
• Isolated cutaneous medium-vessel vasculitis (MVV)
• Cutaneous polyarteritis nodosa (cPAN)
• IgA vasculitis (Henoch-Schönlein purpura, IgAV)

Background

Vasculitis is the swelling or inflammation of your blood vessels. There are many forms of vasculitis, and the cause is unknown for most types of vasculitis. Vasculitis can be isolated to a single body part, or it can involve many different parts of the body or organs. Vasculitis frequently affects the skin and causes different kinds of rashes (lesions).

Because no research studies have provided answers to the question of what therapy for skin vasculitis is best, treatment decisions for patients with skin vasculitis are made based upon the treating doctor’s experience and expert opinions. The doctors involved in this study are hopeful that the information gathered from this study will help doctors and patients understand what the best treatment options are for patients with skin vasculitis.

This study will compare the effectiveness of the three different drugs for the treatment of skin vasculitis, look at how patients respond to the study drugs, and see if there are characteristics that predict which patients will respond to which drugs.

About this Study

About 90 people with skin vasculitis will take part in this study. If you take part in this study, you will be asked to complete a minimum of 6 study visits at the study site. The number of visits will depend upon which stage you enroll into the study and how your skin vasculitis responds to the treatments. You may be in this study for up to 18 months.

This study has two stages, Stage 1 and Stage 2. The study ends after Stage 2. Each Stage is up to 6 months long.

If you are eligible for the study, you will be randomized to take one of the three study drugs: colchicine, dapsone, or azathioprine. You will take this drug for at least 3 months. After that time, if your skin vasculitis is responding (improving) to the drug, you will continue to take this drug for another 6 months (Stage 2), until the end of the study (shown below in Figure 1).

Figure 1

If the treatment you are assigned to in Stage 1 does not help with your vasculitis, you will be randomized again and enter into Stage 2. In Stage 2 you will receive one of the other two treatments you did not receive (shown below in Figure 2). If the new drug given to you in Stage 2 helps with your vasculitis, you can receive this drug for up to 12 months. This means that you could be in the study for up to 18 months.

Figure 2

You may also skip Stage 1 if your disease failed to respond in the past to one of the study drugs, or if you had a bad reaction to the drug. If you skip over Stage 1, you enter the study directly into Stage 2. In Stage 2 you will be randomized to one of the two treatments that you previously did not receive. You will take this drug for at least six months (shown in Figure 3). If this drug helps your vasculitis, you will take this drug for a total of 12 months.

Figure 3

If you do not respond to the new treatment given in Stage 2, you will end your participation in this study and receive care from your treating physician outside of the study (as you normally do).

For each visit, you will be asked to:

• Provide information about your medical history and history of medications used for both your vasculitis and any other medical conditions you may have
• Have a physical exam performed
• Get blood tests done as part of normal routine monitoring / standard of care
• Give a urine sample (some visits)
• Have a chest x-ray (only at the first visit)
• Complete questionnaires about how your vasculitis impacts your life
• Take photographs of your skin lesions
• Complete a study diary to track the doses of the study drug(s) you are taking

Target Enrollment

To be eligible to participate, you must:

• Have isolated skin vasculitis which is vasculitis not associated with any significant problems besides in the skin. To participate, you will need to have a diagnosis of either:
  • Isolated cutaneous small- or medium-vessel vasculitis
  • Cutaneous polyarteritis nodosa (PAN)
  • IgA vasculitis (IgA, formerly Henoch- Schönlein purpura), without active kidney involvement

Having mild joint or muscle pains, leg swelling (edema), fatigue, mild weight loss, low-grade fevers, and mild anemia will be allowed.

• Have a confirmed diagnosis of vasculitis by skin biopsy before enrolling in this study (earlier, at diagnosis, and/or just prior to enrollment) that confirms the diagnosis of vasculitis
• Have active skin vasculitis lasting for at least 1 month continuously and/or have had 2 or more flares over the six months before enrolling
• Have active/ongoing skin vasculitis lesions at the time of enrollment (old scars alone will not be considered active vasculitis)
• Be at least 18 years old

You may still be able to participate in the study if you meet the above requirements even if you have a previous bad side effect to one of the study drugs or were treated in the past with one of the study medications.

You are not eligible to participate if:

• Your vasculitis has significant involvement of other organs besides the skin
  • You have been diagnosed with a form of systemic vasculitis such as granulomatosis with polyangiitis (Wegener's, GPA), eosinophilic granulomatosis with polyangiitis (Churg-Strauss), microscopic polyangiitis (MPA), cryoglobulinemic vasculitis, central nervous system vasculitis, or hypocomplementemic urticarial vasculitis, ​or
  • Other diseases that can cause skin vasculitides such as systemic lupus erythematosus, Sjögren's syndrome, some cancers, some infections, or some medications.
• You have had bad side effects 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 side effects.
• You have evidence of significant liver disease.
• You have evidence of significant low kidney function.
• You have evidence of significant or symptomatic anemia.
• You have another condition that has moderate or high likelihood or requiring treatment with prednisone during the study.
• You have active cancer or history of malignancy within the previous 5 years. Note: If you have been in remission of a cancer for greater than 5 years, or have/had non-metastatic prostate cancer, treated basal or squamous cell carcinoma of the skin, or treated cervical cancer, you may still be able to be enrolled.
• You have an active uncontrolled or serious infection that may stop you from taking or may impact the use of the study medications.
• You are unable to consent (agree to be part of this study)
• You are pregnant or nursing

Note: There are other things that may stop you from being in the study.

How to participate

In order to participate in a study, you must personally contact the study coordinator of any of the participating institutions by phone or by e-mail. Please use the information to the right to inquire about participation.

Note: This is not a Rare Diseases Clinical Research Network-funded study.